WO1997038983A1 - Irreversible inhibitors of tyrosine kinases - Google Patents
Irreversible inhibitors of tyrosine kinases Download PDFInfo
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- WO1997038983A1 WO1997038983A1 PCT/US1997/005778 US9705778W WO9738983A1 WO 1997038983 A1 WO1997038983 A1 WO 1997038983A1 US 9705778 W US9705778 W US 9705778W WO 9738983 A1 WO9738983 A1 WO 9738983A1
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- alkyl
- phenylamino
- amide
- quinazolin
- bromo
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- 0 C*1(C2)C2CCC1 Chemical compound C*1(C2)C2CCC1 0.000 description 6
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A61P17/06—Antipsoriatics
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/00—Antineoplastic agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Definitions
- This invention relates to compounds that are irreversible inhibitors of tyrosine kinases.
- This invention also relates to a method of treating cancer, atherosclerosis, restenosis, endometriosis, and psoriasis, and to a pharmaceutical composition that comprises a compound that is an irreversible inhibitor of tyrosine kinases.
- Cancer has been viewed as a disease of the intracellular signalling system, or signal transduction mechanism.
- Cells receive instructions from many extracellular sources, instructing them to either proliferate or not to proliferate.
- the purpose of the signal transduction system is to receive these and other signals at the cell surface, get them into the cell, and then pass the signals on to the nucleus, the cytoskeleton, and transport and protein synthesis machinery.
- the most common cause of cancer is a series of defects, either in these proteins, when they are mutated, or in the regulation of the quantity of the protein in the cell such that it is over or under produced. Most often, there are key lesions in the cell which lead to a constitutive state whereby the cell nucleus receives a signal to proliferate, when this signal is not actually present.
- the cell may start to produce an authentic growth factor for its own receptors when it should not, the so-called autocrine loop mechanism. Mutations to the cell surface receptors, which usually signal into the cell by means of tyrosine kinases, can lead to activation of the kinase in the absence of ligand, and passing of a signal which is not really there. Alternatively, many surface kinases can be overexpressed on the cell surface leading to an inappropriately strong response to a weak signal. There are many levels inside the cell at which mutation or overexpression can lead to the same spurious signal arising in the cell, and there are many other kinds of signalling defects involved in cancer.
- This invention touches upon cancers which are driven by the three mechanisms just described, and which involve cell surface receptors of the epidermal growth factor receptor tyrosine kinase family (EGFR) .
- This family consists of the EGF receptor (also known as Erb-Bl) , the Erb-B2 receptor, and its constitutively active oncoprotein mutant Neu, the Erb-B3 receptor and the Erb-B4 receptor. Additionally, other biological processes driven through members of the EGF family of receptors can also be treated by compounds of the invention described below.
- the EGFR has as its two most important ligands
- EGF Epidermal Growth Factor
- TGFalpha Transforming Growth Factor alpha
- the receptors appear to have only minor functions in adult humans, but are apparently implicated in the disease process of a large portion of all cancers, especially colon and breast cancer.
- the closely related Erb-B2, Erb-B3, and Erb-B4 receptors have a family of Heregulins as their major ligands, and receptor overexpression and mutation have been unequivocally demonstrated as the major risk factor in poor prognosis breast cancer.
- restenosis is also a disease in which undesired cellular proliferation occurs. Restenosis involves the proliferation of vascular smooth muscle cells. Restenosis is a major clinical problem associated with coronary angioplasty and other medical procedures. Restenosis generally occurs within about 0 to 6 months in about 30% to 50% of patients who undergo balloon angioplasty to clear clogged coronary arteries in an effort to treat heart disease due to occluded arteries . The resulting restenosis causes substantial patient morbidity and health care expense. The process of restenosis is initiated by injury of the blood vessel, including arteries and veins, with the subsequent release of thrombogenic, vasoactive, and mitogenic factors.
- Endothelial and deep vessel injury leads to platelet aggregation, thrombus formation, inflammation, and activation of macrophages and smooth muscle cells. These events induce the production of and release of growth factors and cytokines, which in turn may promote their own synthesis and release from target cells. Thus, a self-perpetuating process involving growth factors such as EGF, platelet derived growth factor (PDGF) or fibroblast growth factor (FGFs) is initiated.
- EGF platelet derived growth factor
- FGFs fibroblast growth factor
- TGF alpha is the major growth factor overproduced in psoriasis, since 50% of transgenic mice which over express TGF alpha develop psoriasis. This suggests that a good inhibitor of EGFR signalling could be used as antipsoriatic agent, preferably, but not necessarily, by topical dosing.
- irreversible tyrosine kinase inhibitors when compared to reversible inhibitors, because irreversible inhibitors can be used in prolonged suppression of the tyrosine kinase, limited only by the normal rate of receptor resynthesis, also called turnover.
- Kurachi H. Morishige K.I., Amemiya K. , Adachi H. , Hirota K., Miyake A., Tanizawa O, Importance Of Transforming Growth Factor Alpha/Epidermal Growth Factor Receptor Autocrine Growth Mechanism In An Ovarian Cancer Cell Line In Vivo, Cancer Res, 1991;51:5956-5959.
- the present invention provides compounds having the Formula I
- X is -SR 4 , halogen, -OR 4 -NHR 3 , or hydrogen, and Y is -D-E-F;
- R 1 is hydrogen, halogen, or C- ⁇ -Cg alkyl
- R 2 , R 3 , and R are independently hydrogen, C ⁇ -Cg alkyl, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl, - (CH 2 ) n -N-L-piperaziny1 [N 4 - (C n -C 6 )alkyl] , - (CH 2 ) n -N-pyrrolidyl, - (CH 2 ) n -pyridinyl,
- a and B are independently hydrogen, C ⁇ -Cg alkyl, -(CH 2 ) n OH,
- Z 1 , 7? 1 , or Z 3 are independently hydrogen, halogen, c l ⁇ c 6 alk Y 1 ' c 3 _c 8 cycloalkyl, C- ⁇ -Cg alkoxy, C 3 -C 8 cycloalkoxy, nitro, C ⁇ -Cg perfluoroalkyl, hydroxy,
- C-L-Cg acyloxy -NH 2 , -NH ⁇ -Cg alkyl), -N(C 1 -Cg alkyl) 2 , -NH(C 3 -C 8 cycloalkyl), -N(C 3 -C 8 cycloalkyl) 2 , hydroxymethyl, C ⁇ -Cg acyl, cyano, azido, C-L-Cg thioalkyl, C ⁇ -Cg sulfinylalkyl, C- j ⁇ Cg sulfonylalkyl, C 3 -C 8 thiocycloalkyl, C 3 ⁇ C 8 sulfinylcycloalkyl, C 3 -C 8 sulfonylcycloalkyl, mercapto, C- ⁇ Cg alkoxycarbonyl, C 3 -C 8 cycloalkoxycarbonyl, C 2 -C 4 alkenyl, C 4 -C
- H -CH CH-(Ci-Cg)alkyl, - (CH 2 ) n -N-hexahydroazepine,
- Formula I, Z and Z ⁇ are hydrogen, and Z J is a halogen.
- Z J is bromine
- the bromine is located at the 3 or meta position of the phenyl ring.
- Z 1 is hydrogen
- Z 2 is F
- Z 3 is Cl .
- Z is hydrogen, Z 2 is F, and Z 3 is Cl, wherein Z 2 is located at the 4 position, and Z 3 is located at the 3 position of the phenyl ring.
- I II II i X is -N-C-C-R-X and Y is hydrogen, or
- I II I ⁇ X is hydrogen, and Y is -N-C-C-R .
- Y is -D-E-F
- -D-E-F is
- X is -D-E-F
- -D-E-F is
- R 2 O R 1 R 5 _ N _p_ c : CH O IR2 ⁇
- R is hydrogen.
- Y is -D-E-F and X is -0 (CH 2 ) n -morpholino.
- R 5 is carboxy, (Ci-Cg alkyl) oxycarbonyl or Ci-Cg alkyl.
- Y is -D-E-F and X is -0 (CH 2 ) n morpholino.
- Y is -D-E-F and X is -0- (CH 2 ) n -Ni ⁇ piperazinyl [N 4 - (C ⁇ Cg) alkyl] .
- Y is -D-E-F and X is -O- (CH 2 ) n -imidazoyl .
- the present invention provides compounds having the Formula II
- p is 0 or 1;
- X is --DD--EE--FF, and Y is -SR 4 , -OR 4 , -NHR 3 or hydrogen, or X is -SR 4 , -OR 4 , -NHR 3 or hydrogen, and Y is
- E is - or -S-;
- R 1 is hydrogen, halogen, or ⁇ -Cg alkyl
- R , R 3 , and R are independently hydrogen, C ⁇ Cg alkyl, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl, - (CH 2 ) n -N a -piperazinyl [N 4 - (C ⁇ -Cg) alkyl] , - (CH 2 ) n -N-pyrrolidyl, - (CH 2 ) n -pyridinyl,
- a and B are independently hydrogen, ⁇ -Cg alkyl, -(CH 2 ) n OH, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl, -(CH 2 ) n -Ni-piperazinyl[N 4 - (Ci-Cg)alkyl] ,
- E 1 , E0, and E? J are independently halogen, C ⁇ Cg alkyl,
- C 3 -C 8 cycloalkyl Ci-Cg alkoxy, C 3 -C 8 cycloalkoxy, nitro, ⁇ -Cg perfluoroalkyl, hydroxy, ⁇ -Cg acyloxy, -NH 2 , -NH(Ci-Cg alkyl), -N(Ci-Cg alkyl) 2 ,
- H -CH CH- (Ci-Cg)alkyl, - (CH 2 ) n -N-hexahydroazepine,
- each Ci-Cg alkyl group can be substituted with -OH, -NH 2 or -NAB, where A and B are as defined above, R 6 is hydrogen or c l -c 6 a lkvl; and n is 1 to 4, p is 0 and 1, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof .
- R 6 is hydrogen or c l -c 6 a lkvl
- n is 1 to 4
- p is 0 and 1
- the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof In a preferred embodiment of the compounds of
- the halogen is bromine.
- the bromine is located at the three or meta position of the phenyl ring.
- E is hydrogen
- E is chlorine
- E 3 is fluorine
- Q is
- the present invention provides compounds having the Formula III
- p is 0 or 1;
- X is -D-E-F
- Y is -SR 4 , -OR 4 , -NHR 3 or hydrogen, or
- X is -SR 4 , -OR 4 , -NHR 3 or hydrogen
- Y is
- R' D is -N- , -0- , -C- , -N N- , -N O- , -C N- , -C O- ,
- R J is hydrogen, halogen, or C i ⁇ Cg alkyl;
- R" R 3 , and R are independently hydrogen, Ci ⁇ Cg alkyl,
- Ci-Cg alkyl wherein the substituents are selected from -0H, -NH 2 , or -N-B, A and B are independently hydrogen, Ci-Cg alkyl, -(CH 2 ) n
- E 1 x , E9* , and E1 J are i•ndependently halogen, C ⁇ Cg alkyl, c 3 _c 8 cycloalkyl, C ⁇ -Cg alkoxy, C 3 -C 8 cycloalkoxy, nitro, Ci ⁇ Cg perfluoroalkyl, hydroxy, C ⁇ -Cg acyloxy, -NH 2 , -NH(Ci ⁇ Cg alkyl), -N(Ci-Cg alkyl) 2 , -NH(C 3 -C 8 cycloalkyl), -N(C 3 -C 8 cycloalkyl) 2 , hydroxymethyl, c i ⁇ Cg acyl, cyano, azido, ⁇ -Cg thioalkyl, C ⁇ Cg sulfinylalkyl
- R is hydrogen, halogen, Ci ⁇ Cg-perfluoroalkyl, 1, l-difluoro(Ci-Cg)alkyl, Ci-Cg alkyl, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) ⁇ -piperazinyl, - (CH 2 ) n -piperazinyl [N 4 - (C ⁇ -Cg) alkyl] , -(CH 2 ) n -N-pyrrolidyl, - (CH 2 ) n -pyridinyl,
- H -CH CH- (Ci-Cg)alkyl, - (CH 2 ) n -N-hexahydroazepine,
- Ci ⁇ Cg alkyl and n is 1 to 4, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
- E 1 and E 2 are hydrogen and E 3 is bromine.
- E 3 is fluorine.
- X is fluorine.
- Q is a . 6-substituted benzothieno[3 , 2-d]pyrmid-4-yl .
- the present invention also provides a pharmaceutically acceptable composition that comprises a compound of Formula I, II, or III.
- the present invention also provides a method of treating cancer, the method comprising administering to a patient having cancer a therapeutically effective amount of a compound of Formula I, II, or III.
- the present invention also provides a method of treating or preventing restenosis, the method comprising administering to a patient having restenosis or at risk of having restenosis, a therapeutically effective amount of a compound of Formula I, II, or III.
- the present invention also provides a method of treating psoriasis, the method comprising administering to a patient having psoriasis a therapeutically effective amount of a compound of Formula I, II, or III.
- the present invention also provides a method of treating atherosclerosis, the method comprising administering to a patient having atherosclerosis a therapeutically effective amount of a compound of Formula I, II, or III.
- the present invention also provides a method of treating endometriosis, the method comprising administering to a patient having endometriosis a therapeutically effective amount of a compound of Formula I, II, or III.
- the present invention also provides a method of irreversibly inhibiting tyrosine kinases, the method comprising administering to a patient in need of tyrosine kinase inhibition a tyrosine kinase inhibiting amount of a compound of Formula I, II or III.
- the present invention provides the following compounds :
- Penta-2, 3-dienoic acid [4- (3-bromo-phenylamino) - quinazolin-6-yl] -amide;
- Propa-1, 2-diene-l-sulfonic acid [4-(3-bromo- phenylamino) -quinazolin-6-yl] -amide;
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido [3, 4-d]pyrimidin-6-yl] -amide; 7-Dimethylamino-hept-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido[3, 4-d]pyrimidin-6-yl] -amide; 7-Morpholin-4-yl-hept-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido[3, 4-d]pyrimidin-6-yl] -amide;
- 5-Dimethylamino-pent-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide
- 5-Morpholin-4-yl-pent-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide;
- Pent-2-enedioic acid 5- ⁇ [2- (4-methyl-piperazin-l- yl) -ethyl] -amide ⁇ 1- ⁇ [4- (1-phenyl-ethylamino) - quinazolin-6-yl] -amide ⁇ ;
- But-2-enedioic acid [4- (3-bromo-phenylamino) - pyrido[3 , 4-d]pyrimidin-6-yl] -amide (3-dimethylamino- propyl) -amide;
- But-2-enedioic acid [4- (3-bromo-phenylamino) - pyrido[3 , 4-d]pyrimidin-6-yl] -amide (3-imidazol-l-yl- propyl) -amide; 4, 4-Difluoro-8-morpholin-4-yl-oct-2-enoic acid
- 6-Morpholin-4-yl-hex-2-ynoic acid [4-(3-bromo- phenylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide;
- But-2-enedioic acid [4- (3-chloro-4-fluoro ⁇ phenylamino) -quinazolin-6-yl] -amide (3-dimethylammo ⁇ propyl) -amide;
- But-2-enedioic acid [4- (3-chloro-4-fluoro- phenylamino) -quinazolin-6-yl] -amide (3-imidazol-l-yl- propyl) -amide;
- 6-Dimethylamino-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -quinazolin-6-yl] -amide
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -quinazolin-6-yl] -amide
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -quinazolin-6-yl] -amide;
- But-2-endioic acid [4- (3-chloro-4- fluorophenylamino) -7-fluoroquinazolin-6-yl]amide (3-dimethylammopropyl)amide;
- But-2-endioic acid [7-chloro-4- (3-chloro-4- fluorophenylamino)quinazolin-6-yl]amide (3-dimethylammopropyl)amide; N- [4- [3- (Bromophenyl)amino] -5-fluoro-7-[3- (4- morpholino)propoxy]quinazolin-6-yl]acrylamide; and N- [4- [ (3- (Chloro-4-fluorophenyl)amino] -5-fluoro-7- (1,N-imidazoyl)propoxy]quinazolin-6-yl]acrylamide.
- the present invention provides compounds having the Formula I
- X is -D-E-F
- Y is -SR 4 , halogen, -OR 4 ,
- X is -SR 4 , halogen, -OR 4 , -NHR 3 , or hydrogen, and Y is -D-E-F;
- E is - or -S-; R 1 * 5
- R 1 is hydrogen, halogen, or C ⁇ Cg alkyl
- R 2 , R 3 , and R 4 are independently hydrogen, C ⁇ Cg alkyl, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl, -(CH 2 ) n -Ni-piperazinyl[N 4 - (Ci-Cg)alkyl] ,
- a and B are independently hydrogen, C ⁇ Cg alkyl, -(CH 2 ) n OH, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl,
- Z , Z 2 , or Z 3 are independently hydrogen, halogen, c l" c 6 alky 1 - c 3" c 8 cycloalkyl, C ⁇ Cg alkoxy, C 3 ⁇ C g cycloalkoxy, nitro, ⁇ -Cg perfluoroalkyl, hydroxy, Ci-Cg acyloxy, -NH 2 , -NH(Ci-Cg alkyl), -N(Ci-C 6 alkyl) 2 , -NH(C 3 -C 8
- R is hydrogen, halogen, Ci ⁇ Cg-perfluoroalkyl, 1, 1-difluoro(Ci-Cg)alkyl, Ci ⁇ Cg alkyl, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -piperazinyl, -(CH 2 ) n -piperazinyl[N 4 - (Ci-Cg)alky
- H -CH CH- (Ci-Cg)alkyl, - (CH 2 ) n -N-hexahydroazepine, -(CH 2 ) n NH 2 ,-(CH 2 ) n NH(Ci-C 6 alkyl) ,
- -I T T selected from Z , Z , Z J or a monocyclic heteroaryl group, and each C ⁇ Cg alkyl group can be substituted with -OH, -NH 2 or -NAB, where A and B are as defined above, R is hydrogen or Ci ⁇ Cg alkyl; R 13 is hydrogen or halogen; and n is 1 to 4, p is 0 or 1, and the pharmaceutically acceptable salts, esters, amides and prodrugs thereof.
- present invention also provides compounds having the Formula II
- p is 0 or 1;
- X is -D-E-F and Y is -SR 4 , -OR 4 , -NHR 3 or hydrogen, or X is -SR 4 , -OR 4 , -NHR 3 or hydrogen, and Y is -D-E-F;
- R is hydrogen, halogen, or ⁇ -Cg alkyl
- R 9 , R3 , and R ⁇ are i •ndependently hydrogen, C ⁇ Cg alkyl, - (CH 2 ) n -N-piperidiny1, - (CH 2 ) n -N-piperazinyl, -(CH 2 ) n -Ni-piperazinyl [N 4 -(C 1 -C 6 )alkyl] , - (CH 2 ) n -N-pyrrolidyl, - (CH 2 ) n -pyridinyl,
- a and B are independently hydrogen, ⁇ -Cg alkyl, -(CH 2 ) n OH, - (CH 2 ) n -N-piperidiny1, - (CH 2 ) n -N-piperazinyl, -(CH 2 ) n -Ni-piperazinyl [N 4 -(Ci-Cg)alkyl] ,
- E 1 x , E9 , and E3 J are independently halogen, C ⁇ Cg alkyl, C 3 -Cg cycloalkyl, ⁇ -Cg alkoxy, C 3 -C 8 cycloalkoxy, nitro, Ci-Cg perfluoroalkyl, hydroxy, Ci ⁇ Cg acyloxy, -NH 2 , -NH(Ci-Cg alkyl), -N(Ci-Cg alkyl) 2 , -NH(C 3 -C 8 cycloalkyl), -N(C 3 -C 8 cycloalkyl) 2 , hydroxymethyl, ⁇ -Cg acyl, cyano, azido, C ⁇ -Cg thioalkyl, Ci ⁇ Cg sulfinylalkyl, Ci ⁇ Cg sulfonylalkyl, C 3 -C 8 thiocycloalkyl, C 3 -C 8 sulfinylcycl
- H -CH CH- (C ⁇ -Cg) alkyl, - (CH 2 ) n -N-hexahydroazepine, -(CH 2 ) n NH 2 ,-(CH 2 ) n NH(Ci-Cg alkyl), -(CH 2 ) n N(Ci-Cg alkyl) 2 , -1-oxo(Ci-Cg)alkyl, carboxy, (Ci ⁇ Cg)alkyloxycarbonyl, N- (Ci ⁇ Cg)alkylcarbamoyl, phenyl or substituted phenyl, wherein the substituted phenyl can have from one to three substituents independently selected from Z 1 , Z9 , Z J 3 or a monocyclic heteroaryl group, and each Ci ⁇ Cg alkyl group can be substituted with -OH, -NH 2 or -NAB, where A and B are as defined above, R is hydrogen or c l
- p is 0 or 1;
- X is -D-E-F
- Y is -SR 4 , -OR 4 , -NHR 3 or hydrogen
- X is -SR 4 , -OR 4 , -NHR 3 or hydrogen
- Y is
- D is -N- -O- -N N-, -N 0-, -C N-, -C 0-,
- R 1 is hydrogen, halogen, or C ⁇ Cg alkyl
- R 2 , R 3 , and R 4 are independently hydrogen, Ci-Cg alkyl, - ⁇ CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl, - (CH 2 ) n -Ni-piperazinyl [N 4 - (Ci-Cg)alkyl] , - (CH 2 ) n -N-pyrrolidyl, - (CH 2 ) n -pyridiny1,
- a and B are independently hydrogen, Ci-Cg alkyl, -(CH 2 ) n OH, - (CH 2 ) n -N-piperidinyl, - (CH 2 ) n -N-piperazinyl, -(CH 2 ) n -Ni-piperazinyl[N 4 - (Ci-Cg alkyl)],
- E 1 , E9, and E J 3 are independently halogen, ⁇ -Cg alkyl, C 3 -C 8 cycloalkyl, C ⁇ Cg alkoxy, C 3 -C 8 cycloalkoxy, nitro, Ci-Cg perfluoroalkyl, hydroxy, ⁇ -Cg acyloxy, -NH 2 , -NH(Ci-Cg alkyl), -N(Ci-Cg alkyl) 2 , -NH(C 3 -C 8 cycloalkyl) , -N(C 3 -C Q cycloalkyl) 2 , hydroxymethyl, ⁇ -Cg acyl, cyano, azido, Ci ⁇ Cg thioalkyl, ⁇ -Cg sulfinylalkyl, Ci-Cg sulfonylalkyl, C 3 -C 8 thiocycloalkyl, C 3 ⁇ C 8 sulfinylcycl
- H -CH CH-(Ci-C 6 )alkyl, - (CH 2 ) n -N-hexahydroazepine,
- Ci ⁇ Cg alkyl and n is 1 to 4, and the pharmaceutically acceptable salts, esters, amides, and prodrugs thereof.
- alkyl means a straight or branched chain hydrocarbon. Representative examples of alkyl groups are methyl, ethyl, propyl, isopropyl, isobutyl, butyl, tert-butyl, sec-butyl, pentyl, and hexyl.
- alkoxy means an alkyl group attached to an oxygen atom.
- Representative examples of alkoxy groups include methoxy, ethoxy, tert-butoxy, propoxy, and isobutoxy.
- halogen includes chlorine, fluorine, bromine, and iodine.
- alkenyl means a branched or straight chain hydrocarbon having one or more carbon-carbon double bond.
- cycloalkyl means a cyclic hydrocarbon. Examples of cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.
- cycloalkoxy means a cycloalkyl group attached to an oxygen atom.
- perfluoroalkyl means an alkyl group in which all the hydrogen atoms have been replaced by fluorine atoms.
- acyl means a group derived from an organic acid by removal of the hydroxy group (-OH) .
- acyloxy means an acyl group attached to an oxygen atom.
- thioalkyl means an alkyl group attached to a sulfur atom.
- sulfinylalkyl means a sulfinyl group attached to an alkyl group.
- sulfonylalkyl means a sulfonyl group attached to an alkyl group.
- thiocycloalkyl means a cycloalkyl group attached to a sulfur atom.
- sulfinylcycloalkyl means a sulfinyl group attached to a cycloalkyl group.
- sulfonylcycloalkyl means a sulfonyl group attached to a cycloalkyl group.
- mercapto means a -SH group.
- alkoxycarbonyl means an alkoxy group attached to a carbonyl group.
- cycloalkoxycarbonyl means a cycloalkyoxy group attached to a carbonyl group.
- cycloalkenyl means a cyclic hydrocarbon containing one or more carbon-carbon double bond.
- alkynyl means a hydrocarbon having one or more carbon-carbon triple bond.
- monocyclic heteroaryl mean a heterocyclic aryl compound having only one ring structure.
- the cyclic compound is aromatic and contains one or more heteroatom.
- heteroatoms include, but are not limited to, nitrogen, oxygen, sulfur, and phosphorus.
- monocyclic heteroaryl groups include, but are not limited to, pyridyl, thienyl, and imidazoyl .
- the symbol "-" represents a covalent bond.
- the compounds of Formulas I, II, and III are irreversible inhibitors of tyrosine kinases, particularly EGF tyrosine kinase.
- a therapeutically effective amount of the compounds of Formula I, II, or III can be administered to a patient having cancer or a patient having restenosis or at risk of having restenosis or a patient having psoriasis, atherosclerosis, or endometriosis.
- Those skilled in the art are readily able to identify patients having cancer, restenosis, psoriasis, atherosclerosis, or endometriosis, and patients who are at risk of developing restenosis.
- the term "patient” means animals such as dogs, cats, cows, sheep, and also includes humans.
- the compounds of the present invention can be administered to humans and animals either orally, rectally, parenterally (intravenously, intramuscularly or subcutaneously) , intracisternally, intravaginally, intraperitoneally, intravesically, locally (powders, ointments, or drops), or as a buccal or nasal spray.
- the compounds can be administered alone or as part of a pharmaceutically acceptable composition that includes pharmaceutically acceptable excipients. It is noted that more than one compound of Formula I, II, III can be administered either concurrently or sequentially.
- compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions.
- suitable aqueous and nonaqueous carriers, diluents, solvents, or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like) , suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate.
- Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.
- These compositions may also contain adjuvants such as preserving, wetting, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.
- Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules.
- the active compound is admixed with at least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or
- fillers or extenders as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid;
- binders as for example, carboxymethylcellulose, alignates, gelatin, polyvinylpyrrolidone, sucrose, and acacia;
- humectants as for example, glycerol;
- disintegrating agents as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain complex silicates, and sodium carbonate;
- solution retarders as for example paraffin
- absorption accelerators as for example, quaternary ammonium compounds
- wetting agents as for example, cetyl alcohol and glycerol monostearate
- adsorbents as for example, kaolin and bentonite
- lubricants as for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof.
- the dosage forms may also comprise buffering agents .
- compositions of a similar type may also be employed as fillers in soft- and hard-filled gelatin capsules using such excipients as lactose or milk sugar, as well as high molecular weight polyethylene ⁇ glycols, and the like.
- Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and others well-known in the art. They may contain opacifying agents, and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Examples of embedding compositions which can be used are polymeric substances and waxes. The active compounds can also be in micro-encapsulated form, if appropriate, with one or more of the above-mentioned excipients .
- Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs.
- the liquid dosage forms may contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1, 3-butyleneglycol, dimethylformamide, oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters of sorbitan or mixtures of these substances, and the like.
- inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, e
- composition can also include adjuvants, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
- adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents.
- Suspensions in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like.
- Compositions for rectal administrations are preferably suppositories which can be prepared by mixing the compounds of the present invention with suitable non-irritating excipients or carriers such as cocoa butter, polyethyleneglycol or a suppository wax, which are solid at ordinary temperatures but liquid at body temperature and therefore, melt in the rectum or vaginal cavity and release the active component.
- Dosage forms for topical administration of a compound of this invention include ointments, powders, sprays, and inhalants.
- the active component is admixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants as may be required.
- Ophthalmic formulations, eye ointments, powders, and solutions are also contemplated as being within the scope of this invention.
- salts refers to those carboxylate salts, amino acid addition salts, esters, amides, and prodrugs of the compounds of the present invention which are, within the scope of sound medical judgement, suitable for use in contact with the tissues of patients without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use, as well as the zwitterionic forms, where possible, of the compounds of the invention.
- salts refers to the relatively non-toxic, inorganic and organic acid addition salts of compounds of the present invention.
- salts can be prepared in situ during the final isolation and purification of the compounds or by separately reacting the purified compound in its free base form with a suitable organic or inorganic acid and isolating the salt thus formed.
- Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactobionate and laurylsulphonate salts, and the like.
- alkali and alkaline earth metals such as sodium, lithium, potassium, calcium, magnesium, and the like
- non-toxic ammonium, quaternary ammonium, and amine cations including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like (see, for example, S.M. Berge, et al. , "Pharmaceutical Salts, " J Pharm Sci , 1977;66:1-19 which is incorporated herein by reference) .
- Examples of pharmaceutically acceptable, non-toxic esters of the compounds of this invention include ⁇ -Cg alkyl esters wherein the alkyl group is a straight or branched chain. Acceptable esters also include C ⁇ -C 7 cycloalkyl esters as well as arylalkyl esters such as, but not limited to benzyl. c i ⁇ C 4 alkyl esters are preferred. Esters of the compounds of the present invention may be prepared according to conventional methods . Examples of pharmaceutically acceptable, non-toxic amides of the compounds of this invention include amides derived from ammonia, primary Ci ⁇ Cg alkyl amines and secondary C ⁇ Cg dialkyl amines wherein the alkyl groups are straight or branched chain.
- the amine may also be in the form of a 5- or 6-membered heterocycle containing one nitrogen atom.
- Amides derived from ammonia, Ci ⁇ C 3 alkyl primary amines and Ci ⁇ C 2 dialkyl secondary amines are preferred. Amides of the compounds of the invention may be prepared according to conventional methods.
- prodrug refers to compounds that are rapidly transformed in vivo to yield the parent compound of the above formulas, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, "Pro-drugs as Novel
- the compounds of the present invention can be administered to a patient at dosage levels in the range of about 0.1 to about 1,000 mg per day. For a normal human adult having a body weight of about 70 kg, a dosage in the range of about 0.01 to about 100 mg per kilogram of body weight per day is sufficient.
- the specific dosage used can vary. For example, the dosage can depend on a number of factors including the requirements of the patient, the severity of the condition being treated, and the pharmacological activity of the compound being used. The determination of optimum dosages for a particular patient is well- known to those skilled in the art.
- the compounds of the present invention can exist in different stereoisometric forms by virtue of the presence of asymmetric centers in the compounds. It is contemplated that all stereoisometric forms of the compounds as well as mixtures thereof, including racemic mixtures, form part of this invention.
- the compounds of the present invention can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the present invention. It is intended that the compounds of Formula I,
- the amine is acylated either by an acid in the presence of a coupling agent such as EDAC, or by an acid chloride.
- the amine in turn can be made by reduction of the corresponding nitro compound, displacement of a halogen by an amine or ammonia equivalent, or in the case of pyrido[4,3-d]pyrimidines by direct incorporation during the synthesis.
- 2-Haloalkylsulfonyl halides form vinyl sulfonamides when treated with the aryl amine and excess tertiary amine base.
- C/N means either a carbon or nitrogen atom is present at that location. means a bond or no bond.
- the hydroxyl group is acylated either by an acid in the presence of a coupling agent such as EDAC, or by an acid chloride.
- the hydroxyl compound can in turn can be made by cleavage of the corresponding methyl ether.
- 3-Methylthioalkanoic acid or their acid chlorides can be used to acylate the oxygen followed by S-alkylation or oxidation and basic or thermal elimination.
- Ar and R denote an aryl group and R denotes an organic group as exemplified herein.
- a Stille or Suzuki coupling can be used to couple the sidechain to an appropriately substituted quinazoline/pyridopyrimidine/pyrimidinopyrimidine/ tricycle.
- quinazoline/pyridopyrimidine/pyrimidinopyrimidine/ tricycle can be made as aryl halides by methods known in the art, or as aryl triflates by triflation of the hydroxyl compounds described above, as aryl stannanes by reaction of the abovementioned triflates with hexamethyl distannane, or as arylboronic acids by conversion of aryl iodides to arylorgano- metallics, followed by treatment with borate esters and hydrolysis.
- aryl iodides can be converted to the arylzinc species and coupled with activated halides.
- Activated halides in pyridopyrimidines and pyrimidinopyrimidines can be displaced by suitable 2-hydroxythiolates, and these in turn can be oxidized to sulfones, and then water eliminated by treatment with mesyl chloride and several equivalents of a base.
- an activated halogen especially fluorine can be used in the sequence just described for pyridopyrimidines, or an aryl iodide precursor can be metalated, quenched with sulfur or a suitable sulfur electrophilic progenitor and then the resultant aryl thiol used to open a terminal epoxide, giving a 2-hydroxy thioether which can be converted onto a vinyl sulfone by oxidation and water elimination as described above.
- Activated halides in pyridopyrimidines and pyrimidinopyrimidines and appropriately substituted quinazolines can be displaced by a (N-alkyl) hydrazine.
- an amino-derivative of the desired ring nucleus can be diazotized, and then reduced to the hydrazine.
- the distal nitrogen of the hydrazine can then be acylated, sulfonylated or phosphorylated, by methods well-known to one skilled in the art.
- Activated halides in pyridopyrimidines and pyrimidinopyrimidines and appropriately substituted quinazolines can be displaced by a suitably O-protected (N-alkyl) hydroxylamine.
- a nitro- derivative of the desired ring nucleus can be synthesized, and then reduced to the hydroxylamine under appropriate mildly reducing conditions.
- the oxygen of the hydroxylamine can then be acylated, sulfonylated or phosphorylated, by methods well-known to one skilled in the art.
- Activated halides in pyridopyrimidines and pyrimidinopyrimidines and appropriately substituted quinazolines can be displaced by cyanide, preferably in the presence of copper or nickel salt catalysis.
- an amino-derivative of the desired ring nucleus can be diazotized, and then converted to the nitrile as described above.
- the nitrile functionality can be incorporated into the heterocycle earlier in the synthesis, either as itself, or via a carboxylic acid or aldehyde, both of which can readily be turned into nitrile compounds by one skilled in the art.
- Reduction of the nitrile to a methyleneamine is followed by nitrogen acylation, sulfonylation or phosphorylation, by methods well-known to one skilled in the art .
- Hydroxymethyl compounds can be incorporated into appropriate heterocycles in many ways obvious to one skilled in the art.
- iodoquinazolines may be carbonylated in a Heck reaction, and then reduced with NaBH 4 to the desired precursor.
- Aminopyridopyrimidines may be diazotized, converted to the nitrile, partially reduced to an imine, hydrolysed, and the resultant aldehyde reduced to hydroxymethyl.
- the oxygen of the hydroxymethyl can then be acylated, sulfonylated or phosphorylated, by methods well-known to one skilled in the art.
- Amino-heterocycles of the type described throughout this application can be alkylated by various double bond-masked equivalents of l-bromobut-3-en-2- one, followed by unmasking of the unsaturation by methods known to one skilled in the art.
- Hydroxy-heterocycles made as described previously from methoxy-heterocycles can be alkylated by various double bond-masked equivalents of l-bromobut-3-en-2- one, followed by unmasking of the unsaturation by methods known to one skilled in the art .
- alkylation of the phenol can be accomplished with chloroacetic acid, followed by conversion to an acyl chloride and Stille coupling of that acyl halide with an appropriate alkenyl stannane.
- Appropriate mercapto-heterocycles made by displacement of activated halides on the heteroaromatic ring, can be alkylated by various double bond-masked equivalents of l-bromobut-3-en-2-one, followed by unmasking of the unsaturation by methods known to one skilled in the art.
- alkylation of the thiol can be accomplished with chloroacetic acid, followed by conversion to an acyl chloride and Stille coupling of that acyl halide with an appropriate alkenyl stannane.
- N- [4- (3-Bromo-phenylamino) -pyrido[4, 3-d]pyrimidin- 7-yl] -N- (3-morpholin-4-yl-propyl) -acrylamide can be made by acylation of 7-amino-4- [ (3-bromophenyl) amino] - pyrido[4, 3-d]pyrimidine [ J Med Chem, 1995:3780] by methods familiar to one skilled in the art.
- acylation with acrylic acid can be achieved through the use of a standard condensing agent such as 1- (3-dimethylammopropyl) -3-ethylcarbodiimide HCl (EDAC) or through the use of acryloyl chloride and a tertiary base such as diisopropyl ethylamine as an acid scavenger.
- a standard condensing agent such as 1- (3-dimethylammopropyl) -3-ethylcarbodiimide HCl (EDAC)
- EDAC 1- (3-dimethylammopropyl) -3-ethylcarbodiimide HCl
- acryloyl chloride and a tertiary base such as diisopropyl ethylamine as an acid scavenger.
- N-alkylation of the acrylamides can then be achieved by methods familiar to one skilled in the art. For example, conversion of the amide to its monoanion by treatment with standard reagents such as sodium hydride followed by displacement on an appropriate halide such as N- (3-chloropropyl)morpholine or N- ⁇ 4- chlorobutyl)morpholine affords the desired alkylated amide.
- standard reagents such as sodium hydride followed by displacement on an appropriate halide such as N- (3-chloropropyl)morpholine or N- ⁇ 4- chlorobutyl)morpholine
- N- [4- (3-bromo-phenylamino) - pyrido[4, 3-d]pyrimidin-7-yl] -N- (3-morpholin-4-yl- propyl) -acrylamide can be made by treating 7-fluoro-4- [ (3-bromophenyl)amino]pyrido- [4, 3-d]pyrimidine with N- (3-aminopropyl)morpholine in dimethylsulfoxide followed by acylation with acrylic acid and a coupling reagent such as 1- (3-dimethylammopropyl) -3- ethylcarbodiimide HCl (EDAC) or acryloyl chloride and a tertiary base such as diisopropyl ethylamine according to methods familiar to those skilled in the art. See, for example, WO 9519774 Al .
- N- (3-Bromo-phenyl) -quinazolin-4-yl-amine was prepared according to methods well-known in the art. See, for example, J Med Chem, 1995;38 (18) :3482-3487.
- N- [4- (3-Bromo-phenylamino) -quinazolin-6-yl]propanamide To a solution of 6-amino-4- [ (3-bromophenyl) amino] quinazoline (157 mg, 0.5 mmol) in dry THF (3 mL) stirred under N 2 at 25°C was added dropwise propionyl chloride (0.05 mL, 0.58 mmol) . A yellow solid formed at once. After 45 minutes the solid was collected by filtration and washed with ether and dried. Recrystallized from wet methanol afforded the desired product (97 mg, 47%), mp 265-266°C.
- 2-Chloro-3-nitrobenzamide DMF (3 drops) was added to a mixture of 2-chloro-3-nitrobezoic acid (0.99 g, 4.9 mmol), oxalyl chloride (0.47 mL, 5.4 mmol) in CH 2 C1 2 (20 mL) at 25°C stirring under N 2 . After gas formation ceased, all the solid went into solution. After 3 hours the solvent was removed under reduced pressure to leave a light yellow solid which was treated with cold NH 4 OH (20 mL) . 2-Chloro-3- nitrobenzamide was collected as an off-white solid (1.02 g, 100%) .
- 6-Nitrobenzothieno[3 ,2-d]pyrimidone A mixture of methyl 3-amino-7-nitrobenzothiophene-2-carboxylate (242 mg, 0.96 mmol) and formamidine acetate (0.51 g,
- A- ( [3-Bromophenyl]amino) -6-nitrobenzothieno [3,2-d]pyrimidine A mixture of 4-chloro-6- nitrobenzothienopyrimidine (166 mg, 0.62 mmol), m-bromoaniline (0.08 mL, 0.73 mmol) and m-bromoaniline hydrochloride (144 mg, 0.69 mmol) in isopropanol (4.5 mL) was heated at 85°C stirring under N 2 for 7.5 hours.
- 6-Amino-4- ( [3-bromophenyl]amino)benzothieno [3,2-d]pyrimidine A solution of 4- ( [3-bromophenyl] amino) -6-nitrobenzothieno[3 , 2-d]pyrimidine (160 mg, 0.4 mmol) in methanol (10 mL) was subjected to hydrogenation with Raney Nickel (0.07 g) at 25°C for 30 hours. After the reaction was done, the solvent was removed under reduced pressure to leave a dark brown solid.
- 2-Fluoro-4-nitrobenzoic acid [25] To a solution of sodium dichromate (3.87 g, 13 mmol) in acetic acid (20 mL) was added 2-fluoro-4-nitrotoluene (1.55 g, 10 mmol) in portions, followed by dropwise addition of concentrated sulfuric acid (10 g) . A strong exotherm was observed (100°C) and the color changed from orange to green. The reaction was heated at 90°C for 1 hour and cooled to 25°C. The reaction mixture was dissolved in water (30 mL) and white crystals formed upon cooling at 0°C. The white solid was collected by filtration washed with cold water and dried to give 2-fluoro- 4-nitrobenzoic acid (0.99 g, 53%) .
- 2-Fluoro-4-nitrobenzamide To a mixture of 2-fluoro-4-nitrobenzoic acid (0.98 g, 5.3 mmol) and oxalyl chloride (0.48 mL, 5.5 mmol) in dichloromethane (25 mL) , stirred under nitrogen at 25°C, was added 3 drops of dimethyl formamide. Gas evolution! The solid slowly dissolved up and after 4 hours the volatiles were removed under reduced pressure. Saturated aqueous ammonia (5 mL) was added to the residue and the mixture was stirred for 10 minutes. The solid was extracted with chloroform (3 x 20 mL) . The combined organic layer was washed with water, saturated brine, and dried (magnesium sulfate) . The solvent was removed under reduced pressure to give 2-fluoro-4-nitrobenzamide (0.83 g, 85%) as a light yellow solid.
- Methyl 3-amino-6-nitrobenzothiophene- 2-carboxylate Methyl thioglycollate (0.08 mL, 0.85 mmol) was added to a solution of 2-fluoro- 4-nitrobenzonitrile (145 mg, 0.87 mmol), and triethylamine (0.14 mL, 1.0 mmol) in acetonitrile (20 mL) stirred under nitrogen at 25°C. After 3 hours further triethylamine (0.28 mL, 2.0 mmol) was added to the solution, which was stirred at 25°C for a further 16 hours.
- 7-Nitrobenzo[b] thieno[3,2-d]-3H-pyrimid-4-one A mixture of methyl 3-amino-6-nitrobenzothiophene- 2-carboxylate (20 mg, 0.08 mmol) and formamidine acetate (59 mg, 0.57 mmol) was heated at 190°C for 5 hours and cooled to 25°C. The reaction residue was triturated with water, and 7-nitrobenzo[b] thieno[3 , 2-d] -3H-pyrimid-4-one (7 mg, 36%) was obtained by Buchner filtration as a dark brown solid, mp >320°C.
- the solid was dissolved in hot ethyl acetate and the solution purified by column chromatography over flash Si0 2 eluting with ethyl acetate. Product fractions were pooled and concentrated to a solid that was triturated in warm ethyl acetate. After cooling, the solids were collected and dried to leave the product (27 mg, 13%) , mp 210-215°C.
- the aqueous phase was further extracted (2x) , then the combined organic phases were washed with brine (2x) , dried (MgS0 4 ) , and filtered through flash Si0 2 .
- the filtrate was concentrated to a solid that was dissolved in warm ethyl acetate.
- the solution was purified by column chromatography over flash Si0 2 eluting with ethyl acetate.
- the product fractions were pooled and concentrated to solid that was triturated in 1:1 ethyl acetate : tert-butyl methyl ether.
- the solids were collected and dried at 0.1 mm/25°C to leave product (30 mg, 18%) of product, mp 165-175°C (dec) following crystallization from ethyl acetate.
- But-2-enedioic acid [4- (3-chloro-4-fluoro- phenylamino) -quinazolin-6-yl] -amide (3-dimethylamino ⁇ propyl) -amide;
- But-2-enedioic acid [4- (3-chloro-4-fluoro- phenylamino) -pyrido[3, 4-d]pyrimidin-6-yl] -amide (3-imidazol-1-yl-propyl) -amide;
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide;
- 5-Dimethylamino-pent-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido [3 , 4-d]pyrimidin-6-yl] -amide
- 5-Morpholin-4-yl-pent-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide;
- But-2-enedioic acid [4- (3-bromo-phenylamino) - pyrido[3 , 4-d]pyrimidin-6-yl] -amide (3-dimethylamino- propyl) -amide;
- But-2-enedioic acid [4- (3-bromo-phenylamino) - pyrido[3 , 4-d]pyrimidin-6-yl] -amide (3-imidazol-l-yl- propyl) -amide;
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-bromo- phenylamino)-pyrido[3 , 4-d]pyrimidin-6-yl] -amide; 7-Dimethylamino-hept-2-ynoic acid [4-(3-bromo- phenylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide;
- But-2-enedioic acid [4- (3-chloro-4-fluoro ⁇ phenylamino) -quinazolin-6-yl] -amide (3-dimethylamino ⁇ propyl) -amide;
- But-2-enedioic acid [4- (3-chloro-4-fluoro- phenylamino) -quinazolin-6-yl] -amide (3-imidazol-l-yl- propyl) -amide; 4, 4-Difluoro-8-morpholin-4-yl-oct-2-enoic acid [4- (3-chloro-4-fluoro-phenylamino) -quinazolin-6-yl] - amide;
- 6-Dimethylamino-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -quinazolin-6-yl] -amide
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -quinazolin-6-yl] -amide
- 6-Morpholin-4-yl-hex-2-ynoic acid [4- (3-chloro-4- fluoro-phenylamino) -quinazolin-6-yl] -amide;
- But-2-enedioic acid [4- (3-bromo-phenylamino)- quinazolin-6-yl] -amide (3-dimethylamino-propyl) -amide;
- But-2-enedioic acid [4- (3-bromo-phenylamino) - quinazolin-6-yl] -amide (3-imidazol-l-yl-propyl) -amide;
- But-2-enedioic acid (4-imidazol-l-yl-butyl) -amide [4- (1-phenyl-ethylamino) -pyrido[3, 4-d]pyrimidin-6-yl] - amide;
- 6-Dimethylamino-hex-2-ynoic acid [4- (1-phenyl- ethylamino) -pyrido[3 , 4-d]pyrimidin-6-yl] -amide; But-2-endioic acid [4- (3-chloro-4- fluorophenylamino) -7-fluoroquinazolin-6-yl] amide (3-dimethylaminopropyl)amide;
- But-2-endioic acid [7-chloro-4- (3-chloro-4- fluorophenylamino)quinazolin-6-yl]amide (3-dimethylaminopropyl)amide;
Abstract
Description
Claims
Priority Applications (22)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
RO98-01475A RO121900B1 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinazes, pharmaceutical composition containing the same and use thereof |
NZ332119A NZ332119A (en) | 1996-04-12 | 1997-04-08 | Quinazoline compounds which are irreversible inhibitors of tyrosine kinases |
AU24463/97A AU725533B2 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
IL12635197A IL126351A0 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
AT97920213T ATE213730T1 (en) | 1996-04-12 | 1997-04-08 | REVERSABLE INHIBITORS OF TYROSINE KINASES |
CA002249446A CA2249446C (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
EA199800887A EA001595B1 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases. |
SK1417-98A SK284073B6 (en) | 1996-04-12 | 1997-04-08 | Polycyclic compounds, use thereof and pharmaceutical compositions on the basis thereof |
HU9901207A HU228446B1 (en) | 1996-04-12 | 1997-04-08 | Kinazoline derivatives as irreversible inhibitors of protein-kinase, pharmaceutical compositions containing these compounds and use thereof |
EE9800328A EE05289B1 (en) | 1996-04-12 | 1997-04-08 | Irreversible Inhibitors of Tyrosine Kinases, Pharmaceutical Composition, Use |
US09/155,501 US6344459B1 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
DE69710712T DE69710712T3 (en) | 1996-04-12 | 1997-04-08 | REVERSIBLE INHIBITORS OF TYROSINE KINASEN |
DK97920213.2T DK0892789T4 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
EP97920213A EP0892789B2 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
JP53717397A JP3370340B2 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinase |
PL97329391A PL190489B1 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
BRPI9708640-1B1A BR9708640B1 (en) | 1996-04-12 | 1997-04-08 | irreversible tyrosine kinase inhibitors and pharmaceutical composition comprising them. |
SI9730304T SI0892789T2 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
BG102811A BG63160B1 (en) | 1996-04-12 | 1998-10-01 | Irreversible tyrosinekinase inhibitors |
NO19984718A NO312588B1 (en) | 1996-04-12 | 1998-10-09 | Irreversible inhibitors of tyrosine kinases, their use and pharmaceutical preparation |
HK99104872A HK1019739A1 (en) | 1996-04-12 | 1999-10-28 | Irreversible inhibitors of tyrosine kinases, theirpharmaceutical use and pharmaceutical composition thereof. |
US10/441,450 US7786131B2 (en) | 1996-04-12 | 2003-05-20 | Pyrimido[5,4-d]pyrimidines derivatives as irreversible inhibitors of tyrosine kinases |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US1535196P | 1996-04-12 | 1996-04-12 | |
US60/015,351 | 1996-04-12 |
Related Child Applications (3)
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US09155501 A-371-Of-International | 1997-04-08 | ||
US09/155,501 A-371-Of-International US6344459B1 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
US09/671,559 Division US6602863B1 (en) | 1996-04-12 | 2000-09-27 | Irreversible inhibitors of tyrosine kinases |
Publications (1)
Publication Number | Publication Date |
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WO1997038983A1 true WO1997038983A1 (en) | 1997-10-23 |
Family
ID=21770892
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PCT/US1997/005778 WO1997038983A1 (en) | 1996-04-12 | 1997-04-08 | Irreversible inhibitors of tyrosine kinases |
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US (3) | US6344459B1 (en) |
EP (1) | EP0892789B2 (en) |
JP (1) | JP3370340B2 (en) |
CN (3) | CN1923818A (en) |
AT (1) | ATE213730T1 (en) |
AU (1) | AU725533B2 (en) |
BG (1) | BG63160B1 (en) |
BR (1) | BR9708640B1 (en) |
CA (1) | CA2249446C (en) |
CZ (1) | CZ295468B6 (en) |
DE (1) | DE69710712T3 (en) |
DK (1) | DK0892789T4 (en) |
EA (1) | EA001595B1 (en) |
EE (1) | EE05289B1 (en) |
ES (1) | ES2174250T5 (en) |
GE (1) | GEP20012442B (en) |
HK (2) | HK1019739A1 (en) |
HU (1) | HU228446B1 (en) |
IL (1) | IL126351A0 (en) |
NO (1) | NO312588B1 (en) |
NZ (1) | NZ332119A (en) |
PL (1) | PL190489B1 (en) |
PT (1) | PT892789E (en) |
RO (1) | RO121900B1 (en) |
SI (1) | SI0892789T2 (en) |
SK (1) | SK284073B6 (en) |
WO (1) | WO1997038983A1 (en) |
ZA (1) | ZA973060B (en) |
Cited By (462)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5760041A (en) * | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
WO1999006396A1 (en) * | 1997-07-29 | 1999-02-11 | Warner-Lambert Company | Irreversible bicyclic inhibitors of tyrosine kinases |
US5929080A (en) * | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
WO1999061444A2 (en) * | 1998-05-26 | 1999-12-02 | Warner-Lambert Company | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
WO2000031048A1 (en) * | 1998-11-19 | 2000-06-02 | Warner-Lambert Company | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
US6127374A (en) * | 1997-07-29 | 2000-10-03 | Warner-Lambert Company | Irreversible inhibitors of tyrosine kinases |
WO2000078735A1 (en) * | 1999-06-21 | 2000-12-28 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, medicaments containing these compounds, their use and methods for the production thereof |
WO2001004111A1 (en) * | 1999-07-09 | 2001-01-18 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
US6184225B1 (en) | 1996-02-13 | 2001-02-06 | Zeneca Limited | Quinazoline derivatives as VEGF inhibitors |
WO2001019369A1 (en) * | 1999-09-14 | 2001-03-22 | Merck Patent Gmbh | Use of thienopyrimidines |
US6251912B1 (en) | 1997-08-01 | 2001-06-26 | American Cyanamid Company | Substituted quinazoline derivatives |
WO2001062743A2 (en) * | 2000-02-26 | 2001-08-30 | Gödecke GmbH | Method for the simplified production of (3-chloro-4-fluoro-phenyl)-[7-(3-morpholino-4-yl-propoxy)-6-nitro-quinazoline-4-yl]-amine or (3-chloro-4-fluoro-phenyl)-[7-(3-morpholino-4-yl-propoxy)-6-amino-quinazoline-4-yl]-amine |
US6291455B1 (en) | 1996-03-05 | 2001-09-18 | Zeneca Limited | 4-anilinoquinazoline derivatives |
WO2001077104A1 (en) * | 2000-04-08 | 2001-10-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocylces, medicaments containing said compounds, the use thereof and method for producing them |
WO2001077085A1 (en) * | 2000-04-07 | 2001-10-18 | Astrazeneca Ab | Quinazoline compounds |
US6323209B1 (en) | 1997-11-06 | 2001-11-27 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
WO2002000630A1 (en) * | 2000-06-30 | 2002-01-03 | Gödecke GmbH | Polymorphic forms/hydrates of n-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide dihydrochloride |
WO2002018375A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Quinazolines, medicaments, which contain these compounds and which are effective as tyrosine kinase inhibitors, their use, and methods for the production thereof |
WO2002018376A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereof |
US6403580B1 (en) | 2000-08-26 | 2002-06-11 | Boehringer Ingelheim Pharma Kg | Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
WO2002050043A1 (en) * | 2000-12-20 | 2002-06-27 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Quinazoline derivatives, medicaments containing said compounds, their utilization and method for the production thereof |
US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
WO2003051884A1 (en) * | 2001-12-18 | 2003-06-26 | Takeda Chemical Industries, Ltd. | Fused indole compound, process for producing the same, and use |
US6627634B2 (en) | 2000-04-08 | 2003-09-30 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
US6664390B2 (en) | 2000-02-02 | 2003-12-16 | Warner-Lambert Company Llc | Method for the simplified production of (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-nitro-quinazoline-4-yl]-amine or (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-amino-quinazoline-4-yl]-amine |
US6673803B2 (en) | 1996-09-25 | 2004-01-06 | Zeneca Limited | Quinazoline derivatives and pharmaceutical compositions containing them |
US6740651B2 (en) | 2000-08-26 | 2004-05-25 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
WO2004060400A1 (en) * | 2003-01-06 | 2004-07-22 | Mitsubishi Pharma Corp | Antipsychotic molecular-targeting epithelial growth factor receptor |
WO2004069791A2 (en) * | 2003-02-05 | 2004-08-19 | Warner-Lambert Company Llc | Preparation of substituted quinazolines |
WO2004103306A2 (en) | 2003-05-19 | 2004-12-02 | Irm Llc | Immunosuppressant compounds and compositions |
WO2005000833A1 (en) | 2003-05-19 | 2005-01-06 | Irm, Llc | Immunosuppressant compounds and compositions |
US6867201B2 (en) * | 1999-01-27 | 2005-03-15 | Pfizer Inc | Heteroaromatic bicyclic derivatives useful as anticancer agents |
US6900221B1 (en) | 1999-11-11 | 2005-05-31 | Osi Pharmaceuticals, Inc. | Stable polymorph on N-(3-ethynylphenyl)-6, 7-bis (2methoxyethoxy)-4-quinazolinamine hydrochloride, methods of production, and pharmaceutical uses thereof |
US6927220B2 (en) | 2001-04-13 | 2005-08-09 | Pfizer Inc | Bicyclic-substituted 4-amino-pyridopyrimidine derivatives |
US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
JP2005526837A (en) * | 2002-04-19 | 2005-09-08 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for their production |
EP1575591A1 (en) * | 2002-12-23 | 2005-09-21 | Ariad Pharmaceuticals, Inc. | Heterocycles and uses thereof |
WO2005107758A1 (en) * | 2004-05-06 | 2005-11-17 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
US7019012B2 (en) | 2000-12-20 | 2006-03-28 | Boehringer Ingelheim International Pharma Gmbh & Co. Kg | Quinazoline derivatives and pharmaceutical compositions containing them |
US7087613B2 (en) | 1999-11-11 | 2006-08-08 | Osi Pharmaceuticals, Inc. | Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride |
WO2006083458A2 (en) | 2004-12-30 | 2006-08-10 | Bioresponse Llc | Use of diindolylmethane-related indoles for the treatment and prevention of respiratory syncytial virus associates conditions |
US7132427B2 (en) | 2001-06-21 | 2006-11-07 | Ariad Pharmaceuticals, Inc. | Quinazolines and uses thereof |
US7196090B2 (en) | 2002-07-25 | 2007-03-27 | Warner-Lambert Company | Kinase inhibitors |
US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
EP1801112A1 (en) * | 1998-05-26 | 2007-06-27 | Warner-Lambert Company LLC | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
WO2007082434A1 (en) | 2006-01-20 | 2007-07-26 | Shanghai Allist Pharmaceutical., Inc. | Quinazoline derivatives,preparation methods and uses thereof |
US7294629B2 (en) | 2001-02-21 | 2007-11-13 | Mitsubishi Pharma Corporation | Quinazoline derivatives |
WO2008037477A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as p13k lipid kinase inhibitors |
EP1944026A2 (en) | 2002-05-16 | 2008-07-16 | Novartis AG | Use of EDG receptor binding agents in cancer |
WO2008098485A1 (en) | 2007-02-14 | 2008-08-21 | Shanghai Allist Pharmaceuticals, Inc. | The salts of 4-aniline quinazoline derivative |
EP1970058A1 (en) | 1998-08-18 | 2008-09-17 | The Regents of the University of California Office of Technology Transfer | Epidermal growth factor receptor antagonists for treating hypersecretion of mucus in the lungs |
US7456189B2 (en) | 2003-09-30 | 2008-11-25 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
EP2022498A2 (en) | 2005-11-21 | 2009-02-11 | Novartis AG | Neuroendocrine tumour treatment |
WO2009030224A2 (en) * | 2007-09-07 | 2009-03-12 | Schebo Biotech Ag | Novel quinazoline compounds and the use thereof for treating cancerous diseases |
EP2042517A1 (en) | 2002-09-27 | 2009-04-01 | Xencor, Inc. | Optimized FC variants and methods for their generation |
EP2042490A2 (en) | 2003-05-16 | 2009-04-01 | AstraZeneca AB | Benzimidazole derivatives as vanilloid receptor antagonists |
US7521456B2 (en) | 1998-04-29 | 2009-04-21 | Osi Pharmaceuticals, Inc. | N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate |
EP2065368A1 (en) | 2004-04-07 | 2009-06-03 | Novartis Ag | Inhibitors of IAP |
US7569577B2 (en) | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
WO2009118292A1 (en) | 2008-03-24 | 2009-10-01 | Novartis Ag | Arylsulfonamide-based matrix metalloprotease inhibitors |
WO2009140863A1 (en) | 2008-05-21 | 2009-11-26 | 上海艾力斯医药科技有限公司 | Compositions comprising quinazoline derivatives, preparation methods and uses thereof |
US7625908B2 (en) | 2003-11-13 | 2009-12-01 | Astrazeneca Ab | Quinazoline derivatives |
US7632840B2 (en) | 2004-02-03 | 2009-12-15 | Astrazeneca Ab | Quinazoline compounds for the treatment of hyperproliferative disorders |
US7659279B2 (en) | 2003-04-30 | 2010-02-09 | Astrazeneca Ab | Quinazoline derivatives and their use in the treatment of cancer |
US7687506B2 (en) | 2003-04-11 | 2010-03-30 | The Regents Of The University Of California | Selective serine/threonine kinase inhibitors |
WO2010043050A1 (en) | 2008-10-16 | 2010-04-22 | Celator Pharmaceuticals Corporation | Combinations of a liposomal water-soluble camptothecin with cetuximab or bevacizumab |
WO2010071794A1 (en) | 2008-12-18 | 2010-06-24 | Novartis Ag | New polymorphic form of 1- (4- { l- [ (e) -4-cyclohexyl--3-trifluoromethyl-benzyloxyimino] -ethyl) -2-ethyl-benzy l) -azetidine-3-carboxylic |
ITMI20082336A1 (en) * | 2008-12-29 | 2010-06-30 | Univ Parma | COMPOUNDS IRREVERSIBLE EGFR INHIBITORS WITH ANTI-PROLIFERATIVE ACTIVITY |
WO2010080455A1 (en) | 2008-12-18 | 2010-07-15 | Novartis Ag | New salts |
WO2010080409A1 (en) | 2008-12-18 | 2010-07-15 | Novartis Ag | Hemifumarate salt of 1- [4- [1- ( 4 -cyclohexyl-3 -trifluoromethyl-benzyloxyimino ) -ethyl] -2 -ethyl-benzyl] -a zetidine-3-carboxylic acid |
WO2010083617A1 (en) | 2009-01-21 | 2010-07-29 | Oncalis Ag | Pyrazolopyrimidines as protein kinase inhibitors |
WO2010088335A1 (en) | 2009-01-29 | 2010-08-05 | Novartis Ag | Substituted benzimidazoles for the treatment of astrocytomas |
WO2010099364A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
WO2010099363A1 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099137A2 (en) | 2009-02-26 | 2010-09-02 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the emt status of tumor cells in vivo |
WO2010107968A1 (en) | 2009-03-18 | 2010-09-23 | Osi Pharmaceuticals, Inc. | Combination cancer therapy comprising administration of an egfr inhibitor and an igf-1r inhibitor |
US7820683B2 (en) | 2005-09-20 | 2010-10-26 | Astrazeneca Ab | 4-(1H-indazol-5-yl-amino)-quinazoline compounds as erbB receptor tyrosine kinase inhibitors for the treatment of cancer |
US7838530B2 (en) | 2003-09-25 | 2010-11-23 | Astrazeneca Ab | Quinazoline derivatives as antiproliferative agents |
EP2253319A1 (en) | 2001-05-16 | 2010-11-24 | Novartis AG | Combination comprising N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2pyrimidine-amine and a chemotherapeutic agent. |
EP2260858A2 (en) | 2003-11-06 | 2010-12-15 | Seattle Genetics, Inc. | Monomethylvaline compounds capable of conjugation to ligands |
EP2263691A1 (en) | 2002-07-15 | 2010-12-22 | Genentech, Inc. | Treatment of cancer with the recombinant humanized monoclonal anti-erbb2 antibody 2C4 (rhuMAb 2C4) |
WO2010149755A1 (en) | 2009-06-26 | 2010-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
US7863281B2 (en) | 2002-04-19 | 2011-01-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
EP2270008A1 (en) | 2005-05-20 | 2011-01-05 | Novartis AG | 1,3-dihydro-imidazo[4,5-c]quinolin-2-ones as lipid kinase and/or pi3 kinases inhibitors |
EP2269603A1 (en) | 2001-02-19 | 2011-01-05 | Novartis AG | Treatment of solid tumours with rapamycin derivatives |
EP2272511A1 (en) | 2006-05-09 | 2011-01-12 | Novartis AG | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof |
WO2011012637A2 (en) | 2009-07-31 | 2011-02-03 | F. Hoffmann-La Roche Ag | Subcutaneous anti-her2 antibody formulation |
WO2011015652A1 (en) | 2009-08-07 | 2011-02-10 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives as c-met tyrosine kinase modulators |
WO2011018454A1 (en) | 2009-08-12 | 2011-02-17 | Novartis Ag | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
EP2286844A2 (en) | 2004-06-01 | 2011-02-23 | Genentech, Inc. | Antibody-drug conjugates and methods |
WO2011020861A1 (en) | 2009-08-20 | 2011-02-24 | Novartis Ag | Heterocyclic oxime compounds |
WO2011022439A1 (en) | 2009-08-17 | 2011-02-24 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
WO2011023677A1 (en) | 2009-08-26 | 2011-03-03 | Novartis Ag | Tetra-substituted heteroaryl compounds and their use as mdm2 and/or mdm4 modulators |
WO2011028135A1 (en) | 2009-09-02 | 2011-03-10 | Auckland Uniservices Limited | Kinase inhibitors, prodrug forms thereof and their use in therapy |
WO2011029915A1 (en) | 2009-09-10 | 2011-03-17 | Novartis Ag | Ether derivatives of bicyclic heteroaryls |
US7910731B2 (en) | 2002-03-30 | 2011-03-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
EP2308855A1 (en) | 2002-03-15 | 2011-04-13 | Novartis AG | 2,4-Diaminopyrimidine derivatives |
EP2314297A1 (en) | 2006-04-05 | 2011-04-27 | Novartis AG | Combinations comprising bcr-abl/c-kit/pdgf-r tk inhibitors for treating cancer |
WO2011054828A1 (en) | 2009-11-04 | 2011-05-12 | Novartis Ag | Heterocyclic sulfonamide derivatives useful as mek inhibitors |
WO2011058164A1 (en) | 2009-11-13 | 2011-05-19 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
US7947676B2 (en) | 2004-12-14 | 2011-05-24 | Astrazeneca Ab | Pyrazolo[3,4-d]pyrimidine compounds as antitumor agents |
WO2011063421A1 (en) | 2009-11-23 | 2011-05-26 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
WO2011064211A1 (en) | 2009-11-25 | 2011-06-03 | Novartis Ag | Benzene-fused 6-membered oxygen-containing heterocyclic derivatives of bicyclic heteroaryls |
WO2011070030A1 (en) | 2009-12-08 | 2011-06-16 | Novartis Ag | Heterocyclic sulfonamide derivatives |
WO2011076786A1 (en) | 2009-12-22 | 2011-06-30 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
US7981418B2 (en) | 2007-03-02 | 2011-07-19 | Genentech, Inc. | Predicting response to a HER inhibitor |
WO2011086053A1 (en) | 2010-01-12 | 2011-07-21 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof |
EP2348110A1 (en) | 2003-05-30 | 2011-07-27 | AstraZeneca UK Limited | Process |
WO2011090940A1 (en) | 2010-01-19 | 2011-07-28 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
US7989462B2 (en) | 2003-07-03 | 2011-08-02 | Myrexis, Inc. | 4-arylamin-or-4-heteroarylamino-quinazolines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
US7998949B2 (en) | 2007-02-06 | 2011-08-16 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof |
EP2359818A1 (en) | 2007-02-15 | 2011-08-24 | Novartis AG | Combination of LBH589 with HSP 90 inhibitors for treating cancer |
WO2011107664A1 (en) | 2010-03-04 | 2011-09-09 | Hospital District Of Southwest Finland | Method for selecting patients for treatment with an egfr inhibitor |
WO2011113802A2 (en) | 2010-03-17 | 2011-09-22 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
EP2368911A1 (en) | 2003-05-02 | 2011-09-28 | Xencor Inc. | Optimized Fc variants and methods for their generation |
WO2011119995A2 (en) | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc. | Formulations and methods of use |
EP2371388A2 (en) | 2004-10-20 | 2011-10-05 | Genentech, Inc. | Antibody formulations |
EP2371822A1 (en) | 2006-03-14 | 2011-10-05 | Novartis AG | Heterobicyclic carboxamides as inhibitors for kinases |
WO2011130654A1 (en) | 2010-04-16 | 2011-10-20 | Genentech, Inc. | Fox03a as predictive biomarker for pi3k/akt kinase pathway inhibitor efficacy |
EP2383297A1 (en) | 2006-08-14 | 2011-11-02 | Xencor Inc. | Optimized antibodies that target CD19 |
EP2386655A2 (en) | 2006-09-12 | 2011-11-16 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using KIT or KDG gene as genetic marker |
US8063187B2 (en) | 2007-05-30 | 2011-11-22 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
US8080558B2 (en) | 2007-10-29 | 2011-12-20 | Natco Pharma Limited | 4-(tetrazol-5-yl)-quinazoline derivatives as anti-cancer agent |
US8080577B2 (en) | 2004-05-06 | 2011-12-20 | Bioresponse, L.L.C. | Diindolylmethane formulations for the treatment of leiomyomas |
WO2011157787A1 (en) | 2010-06-17 | 2011-12-22 | Novartis Ag | Biphenyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
WO2011157793A1 (en) | 2010-06-17 | 2011-12-22 | Novartis Ag | Piperidinyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
EP2399605A1 (en) | 2005-02-23 | 2011-12-28 | Genentech, Inc. | Extending time to disease progression or survival in cancer patients |
US8088782B2 (en) | 2008-05-13 | 2012-01-03 | Astrazeneca Ab | Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A |
WO2012004299A1 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Tetrahydro-pyrido-pyrimidine derivatives |
EP2409969A1 (en) | 2004-06-24 | 2012-01-25 | Novartis AG | Pyrimidine urea derivatives as kinase inhibitors |
EP2423331A2 (en) | 2004-03-31 | 2012-02-29 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
WO2012027960A1 (en) | 2010-08-30 | 2012-03-08 | 山东轩竹医药科技有限公司 | Quinazoline derivatives substituted by aniline, preparation method and use thereof |
WO2012035078A1 (en) | 2010-09-16 | 2012-03-22 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
WO2012035039A1 (en) | 2010-09-15 | 2012-03-22 | F. Hoffmann-La Roche Ag | Azabenzothiazole compounds, compositions and methods of use |
US8178543B2 (en) | 2004-06-02 | 2012-05-15 | Takeda Pharmaceutical Company Limited | Bi- and tricyclic fused pyrimidines as tyrosine kinase inhibitors |
WO2012065161A2 (en) | 2010-11-12 | 2012-05-18 | Scott & White Healthcare | Antibodies to tumor endothelial marker 8 |
WO2012066061A1 (en) | 2010-11-19 | 2012-05-24 | F. Hoffmann-La Roche Ag | Pyrazolopyridines and pyrazolopyridines and their use as tyk2 inhibitors |
WO2012066095A1 (en) | 2010-11-19 | 2012-05-24 | Novartis Ag | Crystalline form of an inhibitor of mdm2/4 and p53 interaction |
EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
WO2012085815A1 (en) | 2010-12-21 | 2012-06-28 | Novartis Ag | Bi-heteroaryl compounds as vps34 inhibitors |
WO2012085176A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Tricyclic pyrazinone compounds, compositions and methods of use thereof as janus kinase inhibitors |
EP2471813A1 (en) | 2004-07-15 | 2012-07-04 | Xencor Inc. | Optimized Fc variants |
WO2012107500A1 (en) | 2011-02-10 | 2012-08-16 | Novartis Ag | [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
WO2012120469A1 (en) | 2011-03-08 | 2012-09-13 | Novartis Ag | Fluorophenyl bicyclic heteroaryl compounds |
WO2012122513A2 (en) | 2011-03-10 | 2012-09-13 | Omeros Corporation | Generation of anti-fn14 monoclonal antibodies by ex-vivo accelerated antibody evolution |
WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
WO2012149014A1 (en) | 2011-04-25 | 2012-11-01 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
WO2012149413A1 (en) | 2011-04-28 | 2012-11-01 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
US8318731B2 (en) | 2007-07-27 | 2012-11-27 | Janssen Pharmaceutica Nv | Pyrrolopyrimidines |
WO2012159457A1 (en) | 2011-05-26 | 2012-11-29 | 山东亨利医药科技有限责任公司 | Quinazoline derivative as tyrosine-kinase inhibitor, preparation method therefor and application thereof |
WO2012168884A1 (en) | 2011-06-09 | 2012-12-13 | Novartis Ag | Heterocyclic sulfonamide derivatives |
WO2012175520A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Hydroxy substituted isoquinolinone derivatives |
WO2012175487A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Cyclohexyl isoquinolinone compounds |
WO2013001445A1 (en) | 2011-06-27 | 2013-01-03 | Novartis Ag | Solid forms and salts of tetrahydro-pyrido-pyrimidine derivatives |
WO2013007768A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors |
WO2013007765A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Fused tricyclic compounds for use as inhibitors of janus kinases |
WO2013024011A1 (en) | 2011-08-12 | 2013-02-21 | F. Hoffmann-La Roche Ag | Indazole compounds, compositions and methods of use |
WO2013033380A1 (en) | 2011-08-31 | 2013-03-07 | Genentech, Inc. | Diagnostic markers |
US8399461B2 (en) | 2006-11-10 | 2013-03-19 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing said compounds, use thereof, and method for production of same |
WO2013038362A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
WO2013041539A1 (en) | 2011-09-20 | 2013-03-28 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
WO2013055530A1 (en) | 2011-09-30 | 2013-04-18 | Genentech, Inc. | Diagnostic methylation markers of epithelial or mesenchymal phenotype and response to egfr kinase inhibitor in tumours or tumour cells |
US8426586B2 (en) | 2003-10-17 | 2013-04-23 | Boehringer Ingelheim International Gmbh | Process for preparing amino crotonyl compounds |
US8431585B2 (en) | 2002-05-11 | 2013-04-30 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy |
EP2592156A2 (en) | 2007-06-08 | 2013-05-15 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
EP2591775A1 (en) | 2006-04-05 | 2013-05-15 | Novartis AG | Combinations comprising mtor inhibitors for treating cancer |
WO2013080141A1 (en) | 2011-11-29 | 2013-06-06 | Novartis Ag | Pyrazolopyrrolidine compounds |
WO2013020024A3 (en) * | 2011-08-03 | 2013-06-13 | Karyopharm Therapeutics, Inc. | Maleimide compounds and methods of treatment |
WO2013096060A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013096055A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013096059A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013093849A1 (en) | 2011-12-22 | 2013-06-27 | Novartis Ag | Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives |
WO2013093850A1 (en) | 2011-12-22 | 2013-06-27 | Novartis Ag | Quinoline derivatives |
WO2013096049A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013096051A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
EP2615183A1 (en) | 2008-05-14 | 2013-07-17 | Genomic Health, Inc. | Predictors of patient response to treatment with EGF receptor inhibitors |
US8492377B2 (en) | 2006-07-13 | 2013-07-23 | Janssen Pharmaceutica Nv | MTKI quinazoline derivatives |
US8497369B2 (en) | 2008-02-07 | 2013-07-30 | Boehringer Ingelheim International Gmbh | Spirocyclic heterocycles medicaments containing said compounds, use thereof and method for their production |
US8507502B2 (en) | 2008-11-10 | 2013-08-13 | National Health Research Institutes | Fused bicyclic and tricyclic pyrimidine compounds as tyrosine kinase inhibitors |
EP2628726A1 (en) | 2008-03-26 | 2013-08-21 | Novartis AG | Hydroxamate-based inhibitors of deacetylases b |
WO2013134743A1 (en) | 2012-03-08 | 2013-09-12 | Halozyme, Inc. | Conditionally active anti-epidermal growth factor receptor antibodies and methods of use thereof |
WO2013148315A1 (en) | 2012-03-27 | 2013-10-03 | Genentech, Inc. | Diagnosis and treatments relating to her3 inhibitors |
WO2013149581A1 (en) | 2012-04-03 | 2013-10-10 | Novartis Ag | Combination products with tyrosine kinase inhibitors and their use |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
US8586621B2 (en) | 2006-10-27 | 2013-11-19 | Michael A. Zeligs | Anti-parasitic methods and compositions utilizing diindolylmethane-related indoles |
WO2013175417A1 (en) | 2012-05-24 | 2013-11-28 | Novartis Ag | Pyrrolopyrrolidinone compounds |
WO2013188763A1 (en) | 2012-06-15 | 2013-12-19 | The Brigham And Women's Hospital, Inc. | Compositions for treating cancer and methods for making the same |
WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
US8648191B2 (en) | 2008-08-08 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
US8669281B1 (en) | 2013-03-14 | 2014-03-11 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US8710104B2 (en) | 2008-11-07 | 2014-04-29 | Triact Therapeutics, Inc. | Catecholic butanes and use thereof for cancer therapy |
WO2014071402A1 (en) | 2012-11-05 | 2014-05-08 | Dana-Farber Cancer Institute, Inc. | Xbp1, cd138, and cs1, pharmaceutical compositions that include the peptides, and methods of using such petides and compositions |
WO2014102630A1 (en) | 2012-11-26 | 2014-07-03 | Novartis Ag | Solid form of dihydro-pyrido-oxazine derivative |
US8772272B2 (en) | 2003-12-18 | 2014-07-08 | Janssen Pharmaceutica Nv | Pyrido-and pyrimidopyrimidine derivatives as anti-proliferative agents |
WO2014115080A1 (en) | 2013-01-22 | 2014-07-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the p53/mdm2 interaction |
WO2014115077A1 (en) | 2013-01-22 | 2014-07-31 | Novartis Ag | Substituted purinone compounds |
WO2014130657A1 (en) | 2013-02-20 | 2014-08-28 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
WO2014128612A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Quinazolin-4-one derivatives |
WO2014139326A1 (en) | 2013-03-13 | 2014-09-18 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
WO2014147246A1 (en) | 2013-03-21 | 2014-09-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
WO2014155268A2 (en) | 2013-03-25 | 2014-10-02 | Novartis Ag | Fgf-r tyrosine kinase activity inhibitors - use in diseases associated with lack of or reduced snf5 activity |
US8852586B2 (en) | 2004-11-12 | 2014-10-07 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
WO2014184778A1 (en) | 2013-05-17 | 2014-11-20 | Novartis Ag | Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof |
US8937158B2 (en) | 2003-03-03 | 2015-01-20 | Xencor, Inc. | Fc variants with increased affinity for FcγRIIc |
WO2015010641A1 (en) | 2013-07-24 | 2015-01-29 | Novartis Ag | Substituted quinazolin-4-one derivatives |
WO2015022663A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
WO2015022664A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
WO2015022662A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
WO2015035062A1 (en) | 2013-09-05 | 2015-03-12 | Genentech, Inc. | Antiproliferative compounds |
WO2015038984A2 (en) | 2013-09-12 | 2015-03-19 | Halozyme, Inc. | Modified anti-epidermal growth factor receptor antibodies and methods of use thereof |
WO2015042078A2 (en) | 2013-09-22 | 2015-03-26 | Calitor Sciences, Llc | Substituted aminopyrimidine compounds and methods of use |
WO2015049325A1 (en) | 2013-10-03 | 2015-04-09 | F. Hoffmann-La Roche Ag | Therapeutic inhibitors of cdk8 and uses thereof |
US9040041B2 (en) | 2005-10-03 | 2015-05-26 | Xencor, Inc. | Modified FC molecules |
US9040548B2 (en) | 1999-11-05 | 2015-05-26 | Astrazeneca Ab | Quinazoline derivatives as VEGF inhibitors |
WO2015084804A1 (en) | 2013-12-03 | 2015-06-11 | Novartis Ag | Combination of mdm2 inhibitor and braf inhibitor and their use |
WO2015095423A2 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
WO2015095418A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
US9073916B2 (en) | 2009-03-11 | 2015-07-07 | Auckland Uniservices Limited | Prodrug forms of kinase inhibitors and their use in therapy |
US9089571B2 (en) | 2005-11-11 | 2015-07-28 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
WO2015145388A2 (en) | 2014-03-27 | 2015-10-01 | Novartis Ag | Methods of treating colorectal cancers harboring upstream wnt pathway mutations |
WO2015153513A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Anti-ox40 antibodies and methods of use |
WO2015153514A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists |
WO2015156674A2 (en) | 2014-04-10 | 2015-10-15 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
US9200079B2 (en) | 2004-11-12 | 2015-12-01 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
WO2016011956A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
WO2016016822A1 (en) | 2014-07-31 | 2016-02-04 | Novartis Ag | Combination therapy |
WO2016036873A1 (en) | 2014-09-05 | 2016-03-10 | Genentech, Inc. | Therapeutic compounds and uses thereof |
WO2016044694A1 (en) | 2014-09-19 | 2016-03-24 | Genentech, Inc. | Use of cbp/ep300 and bet inhibitors for treatment of cancer |
WO2016057924A1 (en) | 2014-10-10 | 2016-04-14 | Genentech, Inc. | Pyrrolidine amide compounds as histone demethylase inhibitors |
WO2016073378A1 (en) | 2014-11-03 | 2016-05-12 | Genentech, Inc. | Assays for detecting t cell immune subsets and methods of use thereof |
WO2016073282A1 (en) | 2014-11-06 | 2016-05-12 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and tigit inhibitors |
WO2016077380A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Substituted pyrrolopyridines as inhibitors of bromodomain |
WO2016077375A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Bromodomain inhibitors and uses thereof |
WO2016077378A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Substituted pyrrolopyrdines as inhibitors of bromodomain |
WO2016081384A1 (en) | 2014-11-17 | 2016-05-26 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
WO2016086200A1 (en) | 2014-11-27 | 2016-06-02 | Genentech, Inc. | 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
WO2016106340A2 (en) | 2014-12-23 | 2016-06-30 | Genentech, Inc. | Compositions and methods for treating and diagnosing chemotherapy-resistant cancers |
US9381246B2 (en) | 2013-09-09 | 2016-07-05 | Triact Therapeutics, Inc. | Cancer therapy |
WO2016109546A2 (en) | 2014-12-30 | 2016-07-07 | Genentech, Inc. | Methods and compositions for prognosis and treatment of cancers |
WO2016112284A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | (piperidin-3-yl)(naphthalen-2-yl)methanone derivatives and related compounds as inhibitors of the histone demethylase kdm2b for the treatment of cancer |
WO2016112298A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | Pyridazinone derivatives and their use in the treatment of cancer |
WO2016112251A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | 4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors |
WO2016123391A1 (en) | 2015-01-29 | 2016-08-04 | Genentech, Inc. | Therapeutic compounds and uses thereof |
WO2016123387A1 (en) | 2015-01-30 | 2016-08-04 | Genentech, Inc. | Therapeutic compounds and uses thereof |
US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
WO2016138114A1 (en) | 2015-02-25 | 2016-09-01 | Genentech, Inc. | Therapeutic pyridazine compounds and uses thereof |
EP3064502A1 (en) | 2012-01-26 | 2016-09-07 | Novartis AG | Imidazopyrrolidinone compounds |
WO2016164480A1 (en) | 2015-04-07 | 2016-10-13 | Genentech, Inc. | Antigen binding complex having agonistic activity and methods of use |
EP3088004A1 (en) | 2004-09-23 | 2016-11-02 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
US9505776B2 (en) | 2013-03-14 | 2016-11-29 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
WO2016196298A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Therapeutic and diagnolstic methods for cancer |
WO2016200836A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies |
WO2016200835A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists |
WO2016205320A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
US9545381B2 (en) | 2009-07-06 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
US9556426B2 (en) | 2009-09-16 | 2017-01-31 | Celgene Avilomics Research, Inc. | Protein kinase conjugates and inhibitors |
WO2017033019A1 (en) | 2015-08-26 | 2017-03-02 | Fundación Centro Nacional De Investigaciones Oncológicas Carlos Iii (Cnio) | Condensed tricyclic compounds as protein kinase inhibitors |
US9585850B2 (en) | 2011-12-23 | 2017-03-07 | Duke University | Methods of treatment using arylcyclopropylamine compounds |
WO2017044434A1 (en) | 2015-09-11 | 2017-03-16 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
US9604922B2 (en) | 2014-02-24 | 2017-03-28 | Alkermes Pharma Ireland Limited | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
US9688691B2 (en) | 2004-12-08 | 2017-06-27 | Janssen Pharmaceutica Nv | Macrocyclic quinazole derivatives and their use as MTKI |
US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US9738643B2 (en) | 2012-08-06 | 2017-08-22 | Duke University | Substituted indazoles for targeting Hsp90 |
EP3208281A1 (en) | 2010-03-29 | 2017-08-23 | Zymeworks, Inc. | Antibodies with enhanced or suppressed effector function |
WO2017151502A1 (en) | 2016-02-29 | 2017-09-08 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2017180581A1 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2017181079A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
WO2017181111A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
WO2017194554A1 (en) | 2016-05-10 | 2017-11-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Combinations therapies for the treatment of cancer |
WO2017205538A1 (en) | 2016-05-24 | 2017-11-30 | Genentech, Inc. | Pyrazolopyridine derivatives for the treatment of cancer |
WO2017205536A2 (en) | 2016-05-24 | 2017-11-30 | Genentech, Inc. | Therapeutic compounds and uses thereof |
US9834575B2 (en) | 2013-02-26 | 2017-12-05 | Triact Therapeutics, Inc. | Cancer therapy |
WO2017214373A1 (en) | 2016-06-08 | 2017-12-14 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2017214452A1 (en) | 2016-06-08 | 2017-12-14 | Xencor, Inc. | Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b |
WO2018027204A1 (en) | 2016-08-05 | 2018-02-08 | Genentech, Inc. | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
WO2018039203A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating multiple myeloma |
WO2018039205A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating breast cancer |
WO2018064076A1 (en) | 2016-09-27 | 2018-04-05 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules |
WO2018068028A1 (en) | 2016-10-06 | 2018-04-12 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
EP3312164A1 (en) | 2014-03-28 | 2018-04-25 | Calitor Sciences, LLC | Substituted heteroaryl compounds and methods of use |
WO2018081648A2 (en) | 2016-10-29 | 2018-05-03 | Genentech, Inc. | Anti-mic antibidies and methods of use |
US10000469B2 (en) | 2014-03-25 | 2018-06-19 | Duke University | Heat shock protein 70 (hsp-70) receptor ligands |
WO2018119183A2 (en) | 2016-12-22 | 2018-06-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2018160841A1 (en) | 2017-03-01 | 2018-09-07 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2018189220A1 (en) | 2017-04-13 | 2018-10-18 | F. Hoffmann-La Roche Ag | An interleukin-2 immunoconjugate, a cd40 agonist, and optionally a pd-1 axis binding antagonist for use in methods of treating cancer |
EP3392274A1 (en) | 2011-08-12 | 2018-10-24 | Omeros Corporation | Anti-fzd10 monoclonal antibodies and methods for their use |
EP3401335A1 (en) | 2008-01-30 | 2018-11-14 | Genentech, Inc. | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
WO2018217651A1 (en) | 2017-05-22 | 2018-11-29 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019018757A1 (en) | 2017-07-21 | 2019-01-24 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
US10196365B2 (en) | 2014-08-15 | 2019-02-05 | Arromax Pharmatech Co., Ltd. | Quinazoline derivative, preparation method therefor, and pharmaceutical composition and application thereof |
WO2019033043A2 (en) | 2017-08-11 | 2019-02-14 | Genentech, Inc. | Anti-cd8 antibodies and uses thereof |
US10207998B2 (en) | 2016-09-29 | 2019-02-19 | Duke University | Substituted benzimidazole and substituted benzothiazole inhibitors of transforming growth factor-β kinase and methods of use thereof |
WO2019051296A1 (en) | 2017-09-08 | 2019-03-14 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2019051291A1 (en) | 2017-09-08 | 2019-03-14 | Amgen Inc. | Inhibitors of kras g12c and methods of using the same |
WO2019067328A1 (en) | 2017-09-26 | 2019-04-04 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules and methods of use |
WO2019083962A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | Peptide vaccines and pembrolizumab for treating breast cancer |
WO2019083960A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | Peptide vaccines and hdac inhibitors for treating multiple myeloma |
WO2019090263A1 (en) | 2017-11-06 | 2019-05-09 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2019099311A1 (en) | 2017-11-19 | 2019-05-23 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
WO2019119486A1 (en) | 2017-12-21 | 2019-06-27 | 中国科学院合肥物质科学研究院 | Class of pyrimidine derivative kinase inhibitors |
WO2019143874A1 (en) | 2018-01-20 | 2019-07-25 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
WO2019148036A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
WO2019148043A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
WO2019148044A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
WO2019165434A1 (en) | 2018-02-26 | 2019-08-29 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
US10426753B2 (en) | 2014-04-03 | 2019-10-01 | Invictus Oncology Pvt. Ltd. | Supramolecular combinatorial therapeutics |
WO2019191339A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Expression vectors for chimeric engulfment receptors, genetically modified host cells, and uses thereof |
WO2019191334A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
WO2019191340A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Cellular immunotherapy compositions and uses thereof |
WO2019213526A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019213516A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019217691A1 (en) | 2018-05-10 | 2019-11-14 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
WO2019226514A2 (en) | 2018-05-21 | 2019-11-28 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
WO2019232419A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019241157A1 (en) | 2018-06-11 | 2019-12-19 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
WO2019246557A1 (en) | 2018-06-23 | 2019-12-26 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor |
WO2020018789A1 (en) | 2018-07-18 | 2020-01-23 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, an antimetabolite, and a platinum agent |
WO2020023628A1 (en) | 2018-07-24 | 2020-01-30 | Hygia Pharmaceuticals, Llc | Compounds, derivatives, and analogs for cancer |
US10584181B2 (en) | 2009-12-04 | 2020-03-10 | Genentech, Inc. | Methods of making and using multispecific antibody panels and antibody analog panels |
WO2020051099A1 (en) | 2018-09-03 | 2020-03-12 | Genentech, Inc. | Carboxamide and sulfonamide derivatives useful as tead modulators |
WO2020050890A2 (en) | 2018-06-12 | 2020-03-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2020061349A1 (en) | 2018-09-21 | 2020-03-26 | Genentech, Inc. | Diagnostic methods for triple-negative breast cancer |
WO2020061060A1 (en) | 2018-09-19 | 2020-03-26 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
WO2020070239A1 (en) | 2018-10-04 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
WO2020081767A1 (en) | 2018-10-18 | 2020-04-23 | Genentech, Inc. | Diagnostic and therapeutic methods for sarcomatoid kidney cancer |
WO2020102730A1 (en) | 2018-11-16 | 2020-05-22 | Amgen Inc. | Improved synthesis of key intermediate of kras g12c inhibitor compound |
WO2020106640A1 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2020106647A2 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Combination therapy including a krasg12c inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers |
WO2020132648A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
WO2020132649A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
WO2020132653A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
WO2020163589A1 (en) | 2019-02-08 | 2020-08-13 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
EP3699290A1 (en) | 2014-12-24 | 2020-08-26 | F. Hoffmann-La Roche AG | Therapeutic, diagnostic, and prognostic methods for cancer |
EP3698807A1 (en) | 2005-01-21 | 2020-08-26 | Genentech, Inc. | Fixed dosing of her antibodies |
WO2020176748A1 (en) | 2019-02-27 | 2020-09-03 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-cd20 or anti-cd38 antibodies |
WO2020172712A1 (en) | 2019-02-27 | 2020-09-03 | Epiaxis Therapeutics Pty Ltd | Methods and agents for assessing t-cell function and predicting response to therapy |
US10767232B2 (en) | 2014-11-03 | 2020-09-08 | Genentech, Inc. | Methods and biomarkers for predicting efficacy and evaluation of an OX40 agonist treatment |
WO2020180770A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
WO2020219906A1 (en) * | 2019-04-25 | 2020-10-29 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of tyrosine kinase |
WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
WO2020226986A2 (en) | 2019-05-03 | 2020-11-12 | Genentech, Inc. | Methods of treating cancer with an anti-pd-l1 antibody |
WO2021017892A1 (en) | 2019-07-26 | 2021-02-04 | 上海复宏汉霖生物技术股份有限公司 | Method and composition for anti-cd73 antibodies and variants |
WO2021026100A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Pyridine derivatives as kif18a inhibitors |
WO2021026101A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
WO2021026098A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
WO2021026099A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
US10927083B2 (en) | 2016-09-29 | 2021-02-23 | Duke University | Substituted benzimidazoles as inhibitors of transforming growth factor-β kinase |
EP3783029A1 (en) | 2015-05-12 | 2021-02-24 | F. Hoffmann-La Roche AG | Therapeutic and diagnostic methods for cancer |
US10935544B2 (en) | 2015-09-04 | 2021-03-02 | Obi Pharma, Inc. | Glycan arrays and method of use |
WO2021046159A1 (en) | 2019-09-04 | 2021-03-11 | Genentech, Inc. | Cd8 binding agents and uses thereof |
WO2021062085A1 (en) | 2019-09-27 | 2021-04-01 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021062245A1 (en) | 2019-09-26 | 2021-04-01 | Exelixis, Inc. | Pyridone compounds and methods of use in the modulation of a protein kinase |
WO2021067875A1 (en) | 2019-10-03 | 2021-04-08 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
US10980894B2 (en) | 2016-03-29 | 2021-04-20 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
WO2021081212A1 (en) | 2019-10-24 | 2021-04-29 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
WO2021083949A1 (en) | 2019-10-29 | 2021-05-06 | F. Hoffmann-La Roche Ag | Bifunctional compounds for the treatment of cancer |
US11000601B2 (en) | 2016-11-21 | 2021-05-11 | Obi Pharma, Inc. | Conjugated biological molecules, pharmaceutical compositions and methods |
WO2021092115A1 (en) | 2019-11-08 | 2021-05-14 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
WO2021091982A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021091956A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021091967A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021092171A1 (en) | 2019-11-06 | 2021-05-14 | Genentech, Inc. | Diagnostic and therapeutic methods for treatment of hematologic cancers |
WO2021097212A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
WO2021097110A1 (en) | 2019-11-13 | 2021-05-20 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2021097256A1 (en) | 2019-11-14 | 2021-05-20 | Cohbar, Inc. | Cxcr4 antagonist peptides |
WO2021097207A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
US11034672B1 (en) | 2018-09-25 | 2021-06-15 | Black Diamond Therapeutics, Inc. | Tyrosine kinase inhibitor compositions, methods of making and methods of use |
WO2021119505A1 (en) | 2019-12-13 | 2021-06-17 | Genentech, Inc. | Anti-ly6g6d antibodies and methods of use |
US11041017B2 (en) | 2016-03-29 | 2021-06-22 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
WO2021127404A1 (en) | 2019-12-20 | 2021-06-24 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
WO2021142026A1 (en) | 2020-01-07 | 2021-07-15 | Revolution Medicines, Inc. | Shp2 inhibitor dosing and methods of treating cancer |
WO2021154761A1 (en) | 2020-01-27 | 2021-08-05 | Genentech, Inc. | Methods for treatment of cancer with an anti-tigit antagonist antibody |
EP3862365A1 (en) | 2016-01-08 | 2021-08-11 | F. Hoffmann-La Roche AG | Methods of treating cea-positive cancers using pd-1 axis binding antagonists and anti-cea/anti-cd3 bispecific antibodies |
WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
WO2021185844A1 (en) | 2020-03-16 | 2021-09-23 | Pvac Medical Technologies Ltd | Use of substance and pharmaceutical composition thereof, and medical treatments or uses thereof |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021202959A1 (en) | 2020-04-03 | 2021-10-07 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2021222167A1 (en) | 2020-04-28 | 2021-11-04 | Genentech, Inc. | Methods and compositions for non-small cell lung cancer immunotherapy |
WO2021233534A1 (en) | 2020-05-20 | 2021-11-25 | Pvac Medical Technologies Ltd | Use of substance and pharmaceutical composition thereof, and medical treatments or uses thereof |
US11203645B2 (en) | 2018-06-27 | 2021-12-21 | Obi Pharma, Inc. | Glycosynthase variants for glycoprotein engineering and methods of use |
WO2021257124A1 (en) | 2020-06-18 | 2021-12-23 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
WO2021257736A1 (en) | 2020-06-18 | 2021-12-23 | Revolution Medicines, Inc. | Methods for delaying, preventing, and treating acquired resistance to ras inhibitors |
WO2021257503A1 (en) | 2020-06-16 | 2021-12-23 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
WO2022002874A1 (en) | 2020-06-30 | 2022-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapy and radical surgery |
WO2022002873A1 (en) | 2020-06-30 | 2022-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapies |
WO2022020716A1 (en) | 2020-07-24 | 2022-01-27 | Genentech, Inc. | Heterocyclic inhibitors of tead for treating cancer |
US11236091B2 (en) | 2019-05-21 | 2022-02-01 | Amgen Inc. | Solid state forms |
WO2022029220A1 (en) | 2020-08-05 | 2022-02-10 | Ellipses Pharma Ltd | Treatment of cancer using a cyclodextrin-containing polymer-topoisomerase inhibitor conjugate and a parp inhibitor |
WO2022031749A1 (en) | 2020-08-03 | 2022-02-10 | Genentech, Inc. | Diagnostic and therapeutic methods for lymphoma |
WO2022036287A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Anti-cd72 chimeric receptors and uses thereof |
WO2022036285A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Compositions and methods for treating cancer with chimeric tim receptors in combination with inhibitors of poly (adp-ribose) polymerase |
WO2022036146A1 (en) | 2020-08-12 | 2022-02-17 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2022036265A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Chimeric tim receptors and uses thereof |
US11261187B2 (en) | 2016-04-22 | 2022-03-01 | Duke University | Compounds and methods for targeting HSP90 |
WO2022047243A1 (en) | 2020-08-27 | 2022-03-03 | Enosi Life Sciences Corp. | Methods and compositions to treat autoimmune diseases and cancer |
WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
EP3822263A4 (en) * | 2018-07-04 | 2022-03-16 | Daiichi Sankyo Company, Limited | Biaryl ether-type quinazoline derivative |
WO2022060583A1 (en) | 2020-09-03 | 2022-03-24 | Revolution Medicines, Inc. | Use of sos1 inhibitors to treat malignancies with shp2 mutations |
WO2022060836A1 (en) | 2020-09-15 | 2022-03-24 | Revolution Medicines, Inc. | Indole derivatives as ras inhibitors in the treatment of cancer |
WO2022066805A1 (en) | 2020-09-23 | 2022-03-31 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
EP3978500A1 (en) | 2015-12-16 | 2022-04-06 | Genentech, Inc. | Process for the preparation of tricyclic pi3k inhibitor compounds |
WO2022076462A1 (en) | 2020-10-05 | 2022-04-14 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2022123316A1 (en) | 2020-12-09 | 2022-06-16 | Takeda Pharmaceutical Company Limited | Compositions of guanylyl cyclase c (gcc) antigen binding agents and methods of use thereof |
WO2022133345A1 (en) | 2020-12-18 | 2022-06-23 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
WO2022140427A1 (en) | 2020-12-22 | 2022-06-30 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
US11401348B2 (en) | 2009-09-02 | 2022-08-02 | Xencor, Inc. | Heterodimeric Fc variants |
WO2022171745A1 (en) | 2021-02-12 | 2022-08-18 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives for the treatment of cancer |
WO2022178205A1 (en) | 2021-02-19 | 2022-08-25 | Exelixis, Inc. | Pyridone compounds and methods of use |
US11426404B2 (en) | 2019-05-14 | 2022-08-30 | Amgen Inc. | Dosing of KRAS inhibitor for treatment of cancers |
WO2022183072A1 (en) | 2021-02-26 | 2022-09-01 | Kelonia Therapeutics, Inc. | Lymphocyte targeted lentiviral vectors |
WO2022235864A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors |
WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
WO2022235870A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
WO2022251296A1 (en) | 2021-05-25 | 2022-12-01 | Erasca, Inc. | Sulfur-containing heteroaromatic tricyclic kras inhibitors |
WO2022266206A1 (en) | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
WO2022266427A1 (en) * | 2021-06-17 | 2022-12-22 | Black Diamond Therapeutics, Inc. | 4-(aryl-methyl-amino)-quinazoline derivatives and uses thereof |
US11542492B2 (en) | 2009-12-30 | 2023-01-03 | Celgene Car Llc | Ligand-directed covalent modification of protein |
WO2023001894A1 (en) | 2021-07-20 | 2023-01-26 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their preparation, and uses |
WO2023010097A1 (en) | 2021-07-28 | 2023-02-02 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
WO2023018699A1 (en) | 2021-08-10 | 2023-02-16 | Erasca, Inc. | Selective kras inhibitors |
US11583577B2 (en) | 2016-04-22 | 2023-02-21 | Obi Pharma, Inc. | Cancer immunotherapy by immune activation or immune modulation via Globo series antigens |
WO2023060253A1 (en) | 2021-10-08 | 2023-04-13 | Revolution Medicines, Inc. | Ras inhibitors |
US11643456B2 (en) | 2016-07-29 | 2023-05-09 | Obi Pharma, Inc. | Human antibodies, pharmaceutical compositions and methods |
US11642400B2 (en) | 2016-07-27 | 2023-05-09 | Obi Pharma, Inc. | Immunogenic/therapeutic glycan compositions and uses thereof |
WO2023097194A2 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2023097195A1 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic indazole compounds and methods of use in the treatment of cancer |
WO2023114954A1 (en) | 2021-12-17 | 2023-06-22 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023144127A1 (en) | 2022-01-31 | 2023-08-03 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon administration, and uses |
EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024030441A1 (en) | 2022-08-02 | 2024-02-08 | National University Corporation Hokkaido University | Methods of improving cellular therapy with organelle complexes |
WO2024033457A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033388A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033389A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033458A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives |
US11932685B2 (en) | 2007-10-31 | 2024-03-19 | Xencor, Inc. | Fc variants with altered binding to FcRn |
WO2024081916A1 (en) | 2022-10-14 | 2024-04-18 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
WO2024085242A2 (en) | 2022-10-21 | 2024-04-25 | Kawasaki Institute Of Industrial Promotion | Non-fouling or super stealth vesicle |
EP4360646A2 (en) | 2015-09-25 | 2024-05-01 | F. Hoffmann-La Roche AG | Anti-tigit antibodies and methods of use |
WO2024091991A1 (en) | 2022-10-25 | 2024-05-02 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
WO2024088808A1 (en) | 2022-10-24 | 2024-05-02 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon intranasal administration, and uses thereof |
Families Citing this family (111)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69710712T3 (en) * | 1996-04-12 | 2010-12-23 | Warner-Lambert Co. Llc | REVERSIBLE INHIBITORS OF TYROSINE KINASEN |
TW436485B (en) * | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
DE10042058A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
US6653305B2 (en) * | 2000-08-26 | 2003-11-25 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
NZ516873A (en) * | 2001-02-12 | 2003-11-28 | Warner Lambert Co | Compositions containing retinoids and erb inhibitors and their use in inhibiting retinoid skin damage |
IL142118A0 (en) * | 2001-03-20 | 2002-03-10 | Prochon Biotech Ltd | Method and composition for treatment of skeletal dysplasias |
EP2277867B1 (en) | 2002-07-15 | 2012-12-05 | Symphony Evolution, Inc. | Compounds, pharmaceutical compositions thereof and their use in treating cancer |
US7740955B2 (en) * | 2003-04-23 | 2010-06-22 | Konica Minolta Holdings, Inc. | Organic electroluminescent device and display |
PA8603801A1 (en) | 2003-05-27 | 2004-12-16 | Janssen Pharmaceutica Nv | DERIVATIVES OF QUINAZOLINE |
WO2005003100A2 (en) * | 2003-07-03 | 2005-01-13 | Myriad Genetics, Inc. | 4-arylamino-quinazolines as activators of caspases and inducers of apoptosis |
EP1660090B1 (en) * | 2003-08-14 | 2012-11-21 | Array Biopharma, Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
US7501427B2 (en) | 2003-08-14 | 2009-03-10 | Array Biopharma, Inc. | Quinazoline analogs as receptor tyrosine kinase inhibitors |
DK2392564T3 (en) * | 2003-09-26 | 2014-01-13 | Exelixis Inc | c-Met modulators and methods of application |
DE10345875A1 (en) * | 2003-09-30 | 2005-04-21 | Boehringer Ingelheim Pharma | Bicyclic heterocycles, pharmaceutical compositions containing them, their use and methods of preparation |
EP2229955A1 (en) * | 2003-10-16 | 2010-09-22 | Imclone LLC | Fibroblast growth factor receptor-1 inhibitors and methods of treatment using the same |
JP2007530654A (en) * | 2004-03-30 | 2007-11-01 | ファイザー・プロダクツ・インク | Signal transduction inhibitor combinations |
US20080268460A1 (en) * | 2004-05-20 | 2008-10-30 | Wyeth | Assays to Identify Irreversibly Binding Inhibitors of Receptor Tyrosine Kinases |
UY29161A1 (en) * | 2004-10-15 | 2006-04-28 | Bayer Pharmaceuticals Corp | NEW HETEROCICLOS |
JO3088B1 (en) * | 2004-12-08 | 2017-03-15 | Janssen Pharmaceutica Nv | Macrocyclic Quinazoline derivatives and their use as MTKI |
US20090155247A1 (en) * | 2005-02-18 | 2009-06-18 | Ashkenazi Avi J | Methods of Using Death Receptor Agonists and EGFR Inhibitors |
US20060188498A1 (en) * | 2005-02-18 | 2006-08-24 | Genentech, Inc. | Methods of using death receptor agonists and EGFR inhibitors |
KR100832593B1 (en) * | 2005-11-08 | 2008-05-27 | 한미약품 주식회사 | Quinazoline derivatives as an signal trnasduction inhibitor and method for the preparation thereof |
DE602006021645D1 (en) | 2005-11-15 | 2011-06-09 | Array Biopharma Inc | Process and intermediates for the preparation of N4-phenyl quinazoline-4-amine derivatives |
CN101100466B (en) * | 2006-07-05 | 2013-12-25 | 天津和美生物技术有限公司 | Non-reversible protein tyrosine phosphorus acylase inhibitor and its preparation and application |
US8246966B2 (en) * | 2006-08-07 | 2012-08-21 | University Of Georgia Research Foundation, Inc. | Trypanosome microsome system and uses thereof |
CA2669531A1 (en) | 2006-11-22 | 2008-06-05 | University Of Georgia Research Foundation, Inc. | Tyrosine kinase inhibitors as anti-kinetolastid and anti-apicomplexan agents |
TW200835497A (en) * | 2007-01-11 | 2008-09-01 | Astrazeneca Ab | Chemical compounds 636 |
EP2217590A4 (en) * | 2007-09-17 | 2011-12-14 | Glaxosmithkline Llc | Pyridopyrimidine derivatives as pi3 kinase inhibitors |
WO2009067543A2 (en) * | 2007-11-19 | 2009-05-28 | The Regents Of The University Of Colorado | Treatment of histone deacetylase mediated disorders |
US8426430B2 (en) * | 2008-06-30 | 2013-04-23 | Hutchison Medipharma Enterprises Limited | Quinazoline derivatives |
BRPI0918970A2 (en) * | 2008-09-05 | 2019-09-24 | Avila Therapeutics Inc | algorithm for irreversible inhibitor design |
SG173014A1 (en) | 2009-01-16 | 2011-08-29 | Exelixis Inc | Malate salt of n- (4- { [ 6, 7-bis (methyloxy) quin0lin-4-yl] oxy}phenyl)-n' - (4 -fluorophenyl) cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer |
KR100963102B1 (en) * | 2009-03-16 | 2010-06-14 | 호서대학교 산학협력단 | Method for screening egfr tyrosine kinase inhibitors, and inhibitors screened by the method |
ES2572728T3 (en) | 2009-03-20 | 2016-06-02 | F. Hoffmann-La Roche Ag | Bispecific anti-HER antibodies |
HUE032582T2 (en) | 2009-05-20 | 2017-09-28 | Biomarin Pharm Inc | Variants of c-type natriuretic peptide |
DK2769737T3 (en) | 2009-07-20 | 2017-07-24 | Bristol Myers Squibb Co | COMBINATION OF ANTI-CTLA4 ANTIBODY WITH ETOPOSIDE FOR SYNERGISTIC TREATMENT OF PROLIFERATIVE DISEASES |
UA108618C2 (en) | 2009-08-07 | 2015-05-25 | APPLICATION OF C-MET-MODULATORS IN COMBINATION WITH THEMOSOLOMID AND / OR RADIATION THERAPY FOR CANCER TREATMENT | |
CN101648890B (en) * | 2009-09-16 | 2012-07-25 | 常州工程职业技术学院 | Synthesis method of 2-fluoro-4-nitrobenzonitrile |
CA2777934A1 (en) | 2009-10-20 | 2011-04-28 | Prometheus Laboratories Inc. | Proximity-mediated assays for detecting oncogenic fusion proteins |
CA2780319A1 (en) | 2009-11-12 | 2011-05-19 | Genentech, Inc. | A method of promoting dendritic spine density |
US9556249B2 (en) | 2010-02-18 | 2017-01-31 | Genentech, Inc. | Neuregulin antagonists and use thereof in treating cancer |
US20120089541A1 (en) | 2010-08-31 | 2012-04-12 | Genentech, Inc. | Biomarkers and methods of treatment |
WO2012154257A1 (en) | 2011-02-17 | 2012-11-15 | Prometheus Laboratories Inc. | Apparatus and method for isolating leukocytes and tumor cells by filtration |
KR20140057326A (en) | 2011-08-17 | 2014-05-12 | 제넨테크, 인크. | Neuregulin antibodies and uses thereof |
RU2019103083A (en) | 2011-11-30 | 2019-03-22 | Дженентек, Инк. | Mutations of ErbB3 in Cancer |
CN103987700B (en) * | 2012-03-09 | 2016-08-31 | 江苏豪森药业集团有限公司 | 4-quinazoline amine derivant and application thereof |
PE20142406A1 (en) | 2012-05-04 | 2015-01-23 | Pfizer | ANTIGENS ASSOCIATED WITH PROSTATE AND VACCINE-BASED IMMUNOTHERAPY REGIMES |
WO2014045310A1 (en) | 2012-09-19 | 2014-03-27 | Massimo Zollo | Pyrimido[5,4-d]pyrimidine or pyrimidine derivatives compounds and uses thereof in the treatment of cancer |
JP2016509045A (en) | 2013-02-22 | 2016-03-24 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | How to treat cancer and prevent drug resistance |
US9925240B2 (en) | 2013-03-06 | 2018-03-27 | Genentech, Inc. | Methods of treating and preventing cancer drug resistance |
SG11201507477XA (en) | 2013-03-14 | 2015-10-29 | Genentech Inc | Combinations of a mek inhibitor compound with an her3/egfr inhibitor compound and methods of use |
CN105307683A (en) | 2013-03-14 | 2016-02-03 | 基因泰克公司 | Methods of treating cancer and preventing cancer drug resistance |
WO2014144850A1 (en) | 2013-03-15 | 2014-09-18 | Genentech, Inc. | Methods of treating cancer and preventing cancer drug resistance |
CN106211774B (en) | 2013-08-02 | 2020-11-06 | 辉瑞公司 | anti-CXCR 4 antibodies and antibody-drug conjugates |
RU2016114074A (en) | 2013-10-18 | 2017-11-23 | Дженентек, Инк. | ANTI-RSPO ANTIBODIES AND METHODS OF APPLICATION |
WO2015108998A2 (en) | 2014-01-15 | 2015-07-23 | The United States Of America, As Represented By The Secretary, Department Of Health & Human Services | Cartilage targeting agents and their use |
RU2016141385A (en) | 2014-03-24 | 2018-04-28 | Дженентек, Инк. | CANCER TREATMENT WITH C-MET ANTAGONISTS AND THEIR CORRELATION WITH HGF EXPRESSION |
WO2016063122A1 (en) | 2014-10-20 | 2016-04-28 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for screening a subject for a cancer |
EP3229836B1 (en) | 2014-12-09 | 2019-11-13 | Institut National de la Sante et de la Recherche Medicale (INSERM) | Human monoclonal antibodies against axl |
WO2016135041A1 (en) | 2015-02-26 | 2016-09-01 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Fusion proteins and antibodies comprising thereof for promoting apoptosis |
JP6739987B2 (en) * | 2015-07-03 | 2020-08-12 | 国立大学法人京都大学 | Nuclear medicine diagnostic imaging agent |
US10029022B2 (en) * | 2015-07-03 | 2018-07-24 | Kyoto University | Nuclear medicine diagnostic imaging agent |
JP2018525029A (en) | 2015-07-07 | 2018-09-06 | インセルム(インスティチュート ナショナル デ ラ サンテ エ デ ラ リシェルシェ メディカル) | Antibody having specificity for myosin 18A and use thereof |
US11385231B2 (en) | 2015-08-27 | 2022-07-12 | Inserm (Institut National De La Sante Et De La Recherche Scientifique) | Methods for predicting the survival time of patients suffering from a lung cancer |
WO2017055324A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of cells of monocytic origin in a tissue sample |
WO2017055322A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of neutrophils in a tissue sample |
WO2017055327A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of endothelial cells in a tissue sample |
WO2017055326A1 (en) | 2015-09-29 | 2017-04-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
CA3013333A1 (en) | 2016-02-26 | 2017-08-31 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Antibodies having specificity for btla and uses thereof |
EP3443004A1 (en) | 2016-04-14 | 2019-02-20 | H. Hoffnabb-La Roche Ag | Anti-rspo3 antibodies and methods of use |
CN106008480A (en) * | 2016-05-19 | 2016-10-12 | 江西科技师范大学 | Quinazoline compound containing cinnamamide structure and preparation method and application thereof |
CA3025057A1 (en) | 2016-05-25 | 2017-11-30 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods and compositions for treating cancers |
CN107488194B (en) * | 2016-06-10 | 2021-07-30 | 山东新时代药业有限公司 | Afatinib intermediate and preparation method thereof |
WO2018011166A2 (en) | 2016-07-12 | 2018-01-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for quantifying the population of myeloid dendritic cells in a tissue sample |
BR112019001693A2 (en) | 2016-07-29 | 2019-07-02 | Ct Hospitalier Universitaire Toulouse | antibodies targeting tumor-associated macrophages and their uses |
CN109843295B (en) | 2016-09-29 | 2022-04-05 | 阿森迪斯药物生长障碍股份有限公司 | Combination therapy with controlled release of CNP agonist |
EP3950709B1 (en) | 2016-10-21 | 2024-02-14 | OSE Immunotherapeutics | Methods for promoting t cells response |
WO2018087391A1 (en) | 2016-11-14 | 2018-05-17 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for modulating stem cells proliferation or differentiation |
CN108148006A (en) * | 2016-12-02 | 2018-06-12 | 北京大学 | Application of the compound containing even acrylamide group in protein inhibitor, protein cross agent or protein label is prepared |
CN110392697A (en) | 2017-03-02 | 2019-10-29 | 国家医疗保健研究所 | There is the antibody and application thereof of specificity to NECTIN-4 |
WO2018185516A1 (en) | 2017-04-05 | 2018-10-11 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cardiovascular toxicity induced by anti-cancer therapy |
WO2018189403A1 (en) | 2017-04-14 | 2018-10-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cancer |
WO2018211007A1 (en) | 2017-05-18 | 2018-11-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of mast cell diseases |
WO2019072888A1 (en) | 2017-10-11 | 2019-04-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting hepatocellular carcinoma treatment response |
WO2019072885A1 (en) | 2017-10-11 | 2019-04-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Magnetic nanoparticles for the treatment of cancer |
US11679148B2 (en) | 2017-11-24 | 2023-06-20 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Methods and compositions for treating cancers |
US11814686B2 (en) | 2017-12-07 | 2023-11-14 | Institut National de la Santéde la Recherche Médicale | Method for screening and treating a subject for a cancer |
WO2019185683A1 (en) | 2018-03-28 | 2019-10-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cancer |
JP2021521445A (en) | 2018-04-13 | 2021-08-26 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | Methods for predicting and treating outcomes in patients with prostate or breast cancer |
WO2019211369A1 (en) | 2018-05-03 | 2019-11-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cancer |
WO2019211370A1 (en) | 2018-05-03 | 2019-11-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for treating cancer |
CA3101694A1 (en) | 2018-05-30 | 2019-12-05 | David MACHOVER | Methods and pharmaceutical compositions for treating cancer |
WO2019234221A1 (en) | 2018-06-08 | 2019-12-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for stratification and treatment of a patient suffering from chronic lymphocytic leukemia |
US20210236633A1 (en) | 2018-08-06 | 2021-08-05 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for treating cancers |
EP3849602A1 (en) | 2018-09-10 | 2021-07-21 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Combination of her2/neu antibody with heme for treating cancer |
CN113490666A (en) | 2018-12-19 | 2021-10-08 | 奥瑞生物药品公司 | Substituted pyrazolo [1,5-A ] pyridine compounds as inhibitors of FGFR tyrosine kinases |
JP2022515197A (en) | 2018-12-19 | 2022-02-17 | アレイ バイオファーマ インコーポレイテッド | 7-((3,5-dimethoxyphenyl) amino) quinoxaline derivative as an FGFR inhibitor for treating cancer |
EP3924520A1 (en) | 2019-02-13 | 2021-12-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions for selecting a cancer treatment in a subject suffering from cancer |
WO2020178400A1 (en) | 2019-03-06 | 2020-09-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method to diagnose a cmmrd |
WO2020234399A1 (en) | 2019-05-20 | 2020-11-26 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Novel anti-cd25 antibodies |
EP4007820A1 (en) | 2019-08-02 | 2022-06-08 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Method for screening a subject for a cancer |
EP3800201A1 (en) | 2019-10-01 | 2021-04-07 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cd28h stimulation enhances nk cell killing activities |
EP4072682A1 (en) | 2019-12-09 | 2022-10-19 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Antibodies having specificity to her4 and uses thereof |
TWI820414B (en) * | 2020-04-17 | 2023-11-01 | 大陸商北京賽特明強醫藥科技有限公司 | Quinazoline compounds, preparation method and use thereof |
CN113527215B (en) * | 2020-04-17 | 2023-12-05 | 北京赛特明强医药科技有限公司 | Quinazoline compound, preparation method and application thereof |
EP4149558A1 (en) | 2020-05-12 | 2023-03-22 | INSERM (Institut National de la Santé et de la Recherche Médicale) | New method to treat cutaneous t-cell lymphomas and tfh derived lymphomas |
WO2022101463A1 (en) | 2020-11-16 | 2022-05-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Use of the last c-terminal residues m31/41 of zikv m ectodomain for triggering apoptotic cell death |
EP4284420A1 (en) | 2021-01-29 | 2023-12-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method to diagnose msi cancer |
US20220389104A1 (en) | 2021-05-28 | 2022-12-08 | Ose Immunotherapeutics | Method for Treating CD127-Positive Cancers by Administering an Anti-CD127 Agent |
WO2024052503A1 (en) | 2022-09-08 | 2024-03-14 | Institut National de la Santé et de la Recherche Médicale | Antibodies having specificity to ltbp2 and uses thereof |
WO2024061930A1 (en) | 2022-09-22 | 2024-03-28 | Institut National de la Santé et de la Recherche Médicale | New method to treat and diagnose peripheral t-cell lymphoma (ptcl) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3755583A (en) * | 1970-06-05 | 1973-08-28 | Chas0!nhx | |
WO1995019774A1 (en) * | 1994-01-25 | 1995-07-27 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
Family Cites Families (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5321030A (en) | 1989-02-14 | 1994-06-14 | Amira, Inc. | Creatine analogs having antiviral activity |
DK0556310T3 (en) * | 1990-11-06 | 1995-08-21 | Pfizer | Quinazoline derivatives to increase antitumor activity |
DK0584222T3 (en) | 1991-05-10 | 1998-02-23 | Rhone Poulenc Rorer Int | Bis-mono and bicyclic aryl and heteroaryl compounds that inhibit EGF and / or PDGF receptor tyrosine kinase |
US5710158A (en) | 1991-05-10 | 1998-01-20 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Aryl and heteroaryl quinazoline compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
US5721237A (en) | 1991-05-10 | 1998-02-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Protein tyrosine kinase aryl and heteroaryl quinazoline compounds having selective inhibition of HER-2 autophosphorylation properties |
NZ243082A (en) | 1991-06-28 | 1995-02-24 | Ici Plc | 4-anilino-quinazoline derivatives; pharmaceutical compositions, preparatory processes, and use thereof |
PT100905A (en) * | 1991-09-30 | 1994-02-28 | Eisai Co Ltd | BICYCLE HYGIENEOUS HETEROCYCLIC COMPOUNDS CONTAINING BENZENE, CYCLOHEXAN OR PYRIDINE AND PYRIMIDINE, PYRIDINE OR IMIDAZOLE SUBSTITUTES AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
GB9300059D0 (en) | 1992-01-20 | 1993-03-03 | Zeneca Ltd | Quinazoline derivatives |
GB9323290D0 (en) | 1992-12-10 | 1994-01-05 | Zeneca Ltd | Quinazoline derivatives |
GB9314884D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Tricyclic derivatives |
GB9314893D0 (en) | 1993-07-19 | 1993-09-01 | Zeneca Ltd | Quinazoline derivatives |
IL112248A0 (en) | 1994-01-25 | 1995-03-30 | Warner Lambert Co | Tricyclic heteroaromatic compounds and pharmaceutical compositions containing them |
US5679683A (en) | 1994-01-25 | 1997-10-21 | Warner-Lambert Company | Tricyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
AU686843B2 (en) | 1994-02-23 | 1998-02-12 | Pfizer Inc. | 4-heterocyclyl-substituted quinazoline derivatives, processes for their preparation and their use as anti-cancer agents |
WO1995024190A2 (en) | 1994-03-07 | 1995-09-14 | Sugen, Inc. | Receptor tyrosine kinase inhibitors for inhibiting cell proliferative disorders and compositions thereof |
DK0682027T3 (en) | 1994-05-03 | 1998-05-04 | Ciba Geigy Ag | Pyrrolopyrimidine derivatives with antiproliferative action |
TW414798B (en) * | 1994-09-07 | 2000-12-11 | Thomae Gmbh Dr K | Pyrimido (5,4-d) pyrimidines, medicaments comprising these compounds, their use and processes for their preparation |
DE4431867A1 (en) * | 1994-09-07 | 1996-03-14 | Thomae Gmbh Dr K | New 4-amino-pyrimido-pyrimidine derivs. |
GB9510757D0 (en) | 1994-09-19 | 1995-07-19 | Wellcome Found | Therapeuticaly active compounds |
TW321649B (en) | 1994-11-12 | 1997-12-01 | Zeneca Ltd | |
AU5108196A (en) | 1995-03-20 | 1996-10-08 | Dr. Karl Thomae Gmbh | Imidazoquinazolines, drugs containing these compounds, their use and process for their preparation |
EP0817775B1 (en) | 1995-03-30 | 2001-09-12 | Pfizer Inc. | Quinazoline derivatives |
GB9508565D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quiazoline derivative |
GB9508535D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivative |
GB9508537D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
GB9508538D0 (en) | 1995-04-27 | 1995-06-14 | Zeneca Ltd | Quinazoline derivatives |
EP0824525B1 (en) | 1995-04-27 | 2001-06-13 | AstraZeneca AB | Quinazoline derivatives |
WO1996040648A1 (en) | 1995-06-07 | 1996-12-19 | Sugen, Inc. | Quinazolines and pharmaceutical compositions |
MX9709867A (en) | 1995-06-07 | 1998-03-31 | Pfizer | Heterocyclic ring-fused pyrimidine derivatives. |
GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
GB9520822D0 (en) | 1995-10-11 | 1995-12-13 | Wellcome Found | Therapeutically active compounds |
AR004010A1 (en) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | HETERO CYCLIC COMPOUNDS |
US6143764A (en) | 1995-11-07 | 2000-11-07 | Kirin Beer Kabushiki Kaisha | Quinoline and quinazoline derivatives inhibiting platelet-derived growth factor receptor autophosphorylation and pharmaceutical compositions containing the same |
PL321296A1 (en) | 1995-11-14 | 1997-12-08 | Pharmacia & Upjohn Spa | Derivatives of aryl and heteroaryl purine |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
US5760041A (en) | 1996-02-05 | 1998-06-02 | American Cyanamid Company | 4-aminoquinazoline EGFR Inhibitors |
IL125686A (en) | 1996-02-13 | 2002-11-10 | Zeneca Ltd | Quinazoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament having an antiangiogenic and/or vascular permeability reducing effect |
GB9603095D0 (en) | 1996-02-14 | 1996-04-10 | Zeneca Ltd | Quinazoline derivatives |
DE69710712T3 (en) * | 1996-04-12 | 2010-12-23 | Warner-Lambert Co. Llc | REVERSIBLE INHIBITORS OF TYROSINE KINASEN |
TW436485B (en) | 1997-08-01 | 2001-05-28 | American Cyanamid Co | Substituted quinazoline derivatives |
-
1997
- 1997-04-08 DE DE69710712T patent/DE69710712T3/en not_active Expired - Lifetime
- 1997-04-08 NZ NZ332119A patent/NZ332119A/en not_active IP Right Cessation
- 1997-04-08 HU HU9901207A patent/HU228446B1/en unknown
- 1997-04-08 CN CNA2006101018277A patent/CN1923818A/en active Pending
- 1997-04-08 IL IL12635197A patent/IL126351A0/en not_active IP Right Cessation
- 1997-04-08 AU AU24463/97A patent/AU725533B2/en not_active Expired
- 1997-04-08 CN CNB2003101141263A patent/CN100503580C/en not_active Expired - Lifetime
- 1997-04-08 AT AT97920213T patent/ATE213730T1/en active
- 1997-04-08 RO RO98-01475A patent/RO121900B1/en unknown
- 1997-04-08 BR BRPI9708640-1B1A patent/BR9708640B1/en not_active IP Right Cessation
- 1997-04-08 US US09/155,501 patent/US6344459B1/en not_active Expired - Lifetime
- 1997-04-08 DK DK97920213.2T patent/DK0892789T4/en active
- 1997-04-08 GE GEAP19974568A patent/GEP20012442B/en unknown
- 1997-04-08 EA EA199800887A patent/EA001595B1/en not_active IP Right Cessation
- 1997-04-08 ES ES97920213T patent/ES2174250T5/en not_active Expired - Lifetime
- 1997-04-08 CA CA002249446A patent/CA2249446C/en not_active Expired - Lifetime
- 1997-04-08 CN CNB97194458XA patent/CN1145614C/en not_active Expired - Lifetime
- 1997-04-08 SI SI9730304T patent/SI0892789T2/en unknown
- 1997-04-08 JP JP53717397A patent/JP3370340B2/en not_active Expired - Lifetime
- 1997-04-08 PL PL97329391A patent/PL190489B1/en unknown
- 1997-04-08 PT PT97920213T patent/PT892789E/en unknown
- 1997-04-08 CZ CZ19983244A patent/CZ295468B6/en not_active IP Right Cessation
- 1997-04-08 EP EP97920213A patent/EP0892789B2/en not_active Expired - Lifetime
- 1997-04-08 WO PCT/US1997/005778 patent/WO1997038983A1/en active IP Right Grant
- 1997-04-08 EE EE9800328A patent/EE05289B1/en unknown
- 1997-04-08 SK SK1417-98A patent/SK284073B6/en not_active IP Right Cessation
- 1997-04-10 ZA ZA9703060A patent/ZA973060B/en unknown
-
1998
- 1998-10-01 BG BG102811A patent/BG63160B1/en unknown
- 1998-10-09 NO NO19984718A patent/NO312588B1/en not_active IP Right Cessation
-
1999
- 1999-10-28 HK HK99104872A patent/HK1019739A1/en not_active IP Right Cessation
-
2000
- 2000-09-27 US US09/671,559 patent/US6602863B1/en not_active Expired - Lifetime
-
2003
- 2003-05-20 US US10/441,450 patent/US7786131B2/en not_active Expired - Fee Related
-
2004
- 2004-10-07 HK HK04107693.1A patent/HK1064675A1/en not_active IP Right Cessation
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3755583A (en) * | 1970-06-05 | 1973-08-28 | Chas0!nhx | |
WO1995019774A1 (en) * | 1994-01-25 | 1995-07-27 | Warner-Lambert Company | Bicyclic compounds capable of inhibiting tyrosine kinases of the epidermal growth factor receptor family |
Cited By (652)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US6184225B1 (en) | 1996-02-13 | 2001-02-06 | Zeneca Limited | Quinazoline derivatives as VEGF inhibitors |
US6291455B1 (en) | 1996-03-05 | 2001-09-18 | Zeneca Limited | 4-anilinoquinazoline derivatives |
US6897210B2 (en) | 1996-09-25 | 2005-05-24 | Zeneca Limited | Quinazoline derivatives and pharmaceutical compositions containing them |
USRE42353E1 (en) | 1996-09-25 | 2011-05-10 | Astrazeneca Uk Limited | Quinazoline derivatives and pharmaceutical compositions containing them |
US6673803B2 (en) | 1996-09-25 | 2004-01-06 | Zeneca Limited | Quinazoline derivatives and pharmaceutical compositions containing them |
US5929080A (en) * | 1997-05-06 | 1999-07-27 | American Cyanamid Company | Method of treating polycystic kidney disease |
US6127374A (en) * | 1997-07-29 | 2000-10-03 | Warner-Lambert Company | Irreversible inhibitors of tyrosine kinases |
US6153617A (en) * | 1997-07-29 | 2000-11-28 | Warner-Lambert Company | Irreversible bicyclic inhibitors of tyrosine kinases |
WO1999006396A1 (en) * | 1997-07-29 | 1999-02-11 | Warner-Lambert Company | Irreversible bicyclic inhibitors of tyrosine kinases |
US6251912B1 (en) | 1997-08-01 | 2001-06-26 | American Cyanamid Company | Substituted quinazoline derivatives |
US6323209B1 (en) | 1997-11-06 | 2001-11-27 | American Cyanamid Company | Method of treating or inhibiting colonic polyps |
US7521456B2 (en) | 1998-04-29 | 2009-04-21 | Osi Pharmaceuticals, Inc. | N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate |
US7501425B1 (en) | 1998-05-26 | 2009-03-10 | Warner Lambert Company | Bicyclic pyrimidines and bicyclic 3,4-dihydropyprimidines as inhibitors of cellular proliferation |
EP1801112A1 (en) * | 1998-05-26 | 2007-06-27 | Warner-Lambert Company LLC | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
WO1999061444A3 (en) * | 1998-05-26 | 2000-02-03 | Warner Lambert Co | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
WO1999061444A2 (en) * | 1998-05-26 | 1999-12-02 | Warner-Lambert Company | Bicyclic pyrimidines and bicyclic 3,4-dihydropyrimidines as inhibitors of cellular proliferation |
EP1970058A1 (en) | 1998-08-18 | 2008-09-17 | The Regents of the University of California Office of Technology Transfer | Epidermal growth factor receptor antagonists for treating hypersecretion of mucus in the lungs |
WO2000031048A1 (en) * | 1998-11-19 | 2000-06-02 | Warner-Lambert Company | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, an irreversible inhibitor of tyrosine kinases |
US6344455B1 (en) * | 1998-11-19 | 2002-02-05 | Warner-Lambert Company | N-[4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl-propoxy)-quinazolin-6-yl]-acrylamide, and irreversible inhibitor of tyrosine kinases |
AU763626B2 (en) * | 1998-11-19 | 2003-07-31 | Warner-Lambert Company | N-(4-(3-chloro-4-fluoro-phenylamino)-7-(3-morpholin-4-yl- propoxy)-quinazolin-6-yl)-acrylamide, an irreversible inhibitor of tyrosine kinases |
US6867201B2 (en) * | 1999-01-27 | 2005-03-15 | Pfizer Inc | Heteroaromatic bicyclic derivatives useful as anticancer agents |
US7220750B2 (en) | 1999-06-21 | 2007-05-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
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EP1731511A1 (en) * | 1999-06-21 | 2006-12-13 | Boehringer Ingelheim Pharma GmbH & Co. KG | BicyclischeI heterocycles, medicaments containing these compounds, their use and methods for the production thereof |
WO2000078735A1 (en) * | 1999-06-21 | 2000-12-28 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, medicaments containing these compounds, their use and methods for the production thereof |
KR100709909B1 (en) * | 1999-06-21 | 2007-04-24 | 베링거 잉겔하임 파르마 게엠베하 운트 코 카게 | Bicyclic heterocycles, medicaments containing these compounds and methods for the production thereof |
CZ302365B6 (en) * | 1999-06-21 | 2011-04-13 | Boehringer Ingelheim Pharma Gmbh & Co. Kg. | Bicyclic, heterocyclic compounds, pharmaceutical preparation containing such compounds, their use and preparation process thereof |
US8722694B2 (en) | 1999-06-21 | 2014-05-13 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
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US7507741B2 (en) | 1999-07-09 | 2009-03-24 | Smithkline Beecham Corporation | Heterocyclic compounds |
US7189734B2 (en) | 1999-07-09 | 2007-03-13 | Smithkline Beecham Corporation | Anilinoquinazaolines as protein tyrosine kianse inhibitors |
US7265123B2 (en) | 1999-07-09 | 2007-09-04 | Smithkline Beecham Corporation | Heterocyclic compounds |
US7084147B2 (en) | 1999-07-09 | 2006-08-01 | Smithkline Beecham Corporation | Anilinoquinazaolines as protein tyrosine kinase inhibitors |
US6933299B1 (en) | 1999-07-09 | 2005-08-23 | Smithkline Beecham Corporation | Anilinoquinazolines as protein tyrosine kinase inhibitors |
WO2001004111A1 (en) * | 1999-07-09 | 2001-01-18 | Glaxo Group Limited | Anilinoquinazolines as protein tyrosine kinase inhibitors |
US6432979B1 (en) | 1999-08-12 | 2002-08-13 | American Cyanamid Company | Method of treating or inhibiting colonic polyps and colorectal cancer |
WO2001019369A1 (en) * | 1999-09-14 | 2001-03-22 | Merck Patent Gmbh | Use of thienopyrimidines |
US9040548B2 (en) | 1999-11-05 | 2015-05-26 | Astrazeneca Ab | Quinazoline derivatives as VEGF inhibitors |
US10457664B2 (en) | 1999-11-05 | 2019-10-29 | Genzyme Corporation | Quinazoline derivatives as VEGF inhibitors |
US7087613B2 (en) | 1999-11-11 | 2006-08-08 | Osi Pharmaceuticals, Inc. | Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride |
US6900221B1 (en) | 1999-11-11 | 2005-05-31 | Osi Pharmaceuticals, Inc. | Stable polymorph on N-(3-ethynylphenyl)-6, 7-bis (2methoxyethoxy)-4-quinazolinamine hydrochloride, methods of production, and pharmaceutical uses thereof |
US6664390B2 (en) | 2000-02-02 | 2003-12-16 | Warner-Lambert Company Llc | Method for the simplified production of (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-nitro-quinazoline-4-yl]-amine or (3-chloro-4-fluorophenyl)-[7-(3-morpholin-4-yl-propoxy)-6-amino-quinazoline-4-yl]-amine |
WO2001062743A3 (en) * | 2000-02-26 | 2002-03-14 | Goedecke Gmbh | Method for the simplified production of (3-chloro-4-fluoro-phenyl)-[7-(3-morpholino-4-yl-propoxy)-6-nitro-quinazoline-4-yl]-amine or (3-chloro-4-fluoro-phenyl)-[7-(3-morpholino-4-yl-propoxy)-6-amino-quinazoline-4-yl]-amine |
WO2001062743A2 (en) * | 2000-02-26 | 2001-08-30 | Gödecke GmbH | Method for the simplified production of (3-chloro-4-fluoro-phenyl)-[7-(3-morpholino-4-yl-propoxy)-6-nitro-quinazoline-4-yl]-amine or (3-chloro-4-fluoro-phenyl)-[7-(3-morpholino-4-yl-propoxy)-6-amino-quinazoline-4-yl]-amine |
WO2001077085A1 (en) * | 2000-04-07 | 2001-10-18 | Astrazeneca Ab | Quinazoline compounds |
AU779695B2 (en) * | 2000-04-07 | 2005-02-10 | Astrazeneca Ab | Quinazoline compounds |
WO2001077104A1 (en) * | 2000-04-08 | 2001-10-18 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocylces, medicaments containing said compounds, the use thereof and method for producing them |
JP2003530395A (en) * | 2000-04-08 | 2003-10-14 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and methods for their preparation |
US6627634B2 (en) | 2000-04-08 | 2003-09-30 | Boehringer Ingelheim Pharma Kg | Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them |
WO2002000630A1 (en) * | 2000-06-30 | 2002-01-03 | Gödecke GmbH | Polymorphic forms/hydrates of n-[4-(3-chloro-4-fluorophenylamino)-7-(3-morpholin-4-ylpropoxy)-quinazolin-6-yl]-acrylamide dihydrochloride |
US6740651B2 (en) | 2000-08-26 | 2004-05-25 | Boehringer Ingelheim Pharma Kg | Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases |
US6403580B1 (en) | 2000-08-26 | 2002-06-11 | Boehringer Ingelheim Pharma Kg | Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
WO2002018376A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, medicaments containing these compounds, their use, and methods for the production thereof |
WO2002018375A1 (en) * | 2000-08-26 | 2002-03-07 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Quinazolines, medicaments, which contain these compounds and which are effective as tyrosine kinase inhibitors, their use, and methods for the production thereof |
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US8410131B2 (en) | 2001-02-19 | 2013-04-02 | Novartis Pharmaceuticals Corporation | Cancer treatment |
EP2762140A1 (en) | 2001-02-19 | 2014-08-06 | Novartis AG | Treatment of solid brain tumours with a rapamycin derivative |
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EP3345602A1 (en) | 2001-02-19 | 2018-07-11 | Novartis AG | Rapamycin derivative for treating advanced solid tumours |
EP3342411A1 (en) | 2001-02-19 | 2018-07-04 | Novartis AG | Rapamycin derivative for treating pancreas cancer |
EP3406249A1 (en) | 2001-02-19 | 2018-11-28 | Novartis AG | Treatment of breast tumors with a rapamycin derivative in combination with an aromatase inhibitor |
US8877771B2 (en) | 2001-02-19 | 2014-11-04 | Novartis Pharmaceuticals Corporation | Treatment of solid tumors with rapamycin derivatives |
EP2783686A1 (en) | 2001-02-19 | 2014-10-01 | Novartis AG | Combination of a rapamycin derivative and letrozole for treating breast cancer |
EP2764865A2 (en) | 2001-02-19 | 2014-08-13 | Novartis AG | Cancer treatment |
EP2269604A1 (en) | 2001-02-19 | 2011-01-05 | Novartis AG | Treatment of solid tumours with rapamycin derivatives |
EP2269603A1 (en) | 2001-02-19 | 2011-01-05 | Novartis AG | Treatment of solid tumours with rapamycin derivatives |
US7294629B2 (en) | 2001-02-21 | 2007-11-13 | Mitsubishi Pharma Corporation | Quinazoline derivatives |
US6927220B2 (en) | 2001-04-13 | 2005-08-09 | Pfizer Inc | Bicyclic-substituted 4-amino-pyridopyrimidine derivatives |
EP2253319A1 (en) | 2001-05-16 | 2010-11-24 | Novartis AG | Combination comprising N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2pyrimidine-amine and a chemotherapeutic agent. |
US7132427B2 (en) | 2001-06-21 | 2006-11-07 | Ariad Pharmaceuticals, Inc. | Quinazolines and uses thereof |
WO2003051884A1 (en) * | 2001-12-18 | 2003-06-26 | Takeda Chemical Industries, Ltd. | Fused indole compound, process for producing the same, and use |
EP2308855A1 (en) | 2002-03-15 | 2011-04-13 | Novartis AG | 2,4-Diaminopyrimidine derivatives |
US8343982B2 (en) | 2002-03-30 | 2013-01-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocyclic compounds pharmaceutical compositions containing these compounds, their use and process for preparing the same |
US7910731B2 (en) | 2002-03-30 | 2011-03-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
US7863281B2 (en) | 2002-04-19 | 2011-01-04 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof |
JP2005526837A (en) * | 2002-04-19 | 2005-09-08 | ベーリンガー インゲルハイム ファルマ ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for their production |
US8431585B2 (en) | 2002-05-11 | 2013-04-30 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy |
EP1944026A2 (en) | 2002-05-16 | 2008-07-16 | Novartis AG | Use of EDG receptor binding agents in cancer |
EP1955696A2 (en) | 2002-05-16 | 2008-08-13 | Novartis AG | Use of EDG receptor binding agents in cancer |
EP2263691A1 (en) | 2002-07-15 | 2010-12-22 | Genentech, Inc. | Treatment of cancer with the recombinant humanized monoclonal anti-erbb2 antibody 2C4 (rhuMAb 2C4) |
US7196090B2 (en) | 2002-07-25 | 2007-03-27 | Warner-Lambert Company | Kinase inhibitors |
EP3502133A1 (en) | 2002-09-27 | 2019-06-26 | Xencor, Inc. | Optimized fc variants and methods for their generation |
EP2298805A2 (en) | 2002-09-27 | 2011-03-23 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
EP2042517A1 (en) | 2002-09-27 | 2009-04-01 | Xencor, Inc. | Optimized FC variants and methods for their generation |
EP2364996A1 (en) | 2002-09-27 | 2011-09-14 | Xencor Inc. | Optimized FC variants and methods for their generation |
EP3321282A1 (en) | 2002-09-27 | 2018-05-16 | Xencor, Inc. | Optimized fc variants and methods for their generation |
EP2345671A1 (en) | 2002-09-27 | 2011-07-20 | Xencor Inc. | Optimized fc variants and methods for their generation |
EP3150630A1 (en) | 2002-09-27 | 2017-04-05 | Xencor Inc. | Optimized fc variants and methods for their generation |
EP1575591A4 (en) * | 2002-12-23 | 2007-09-12 | Ariad Pharma Inc | Heterocycles and uses thereof |
EP1575591A1 (en) * | 2002-12-23 | 2005-09-21 | Ariad Pharmaceuticals, Inc. | Heterocycles and uses thereof |
US7238679B2 (en) * | 2002-12-23 | 2007-07-03 | Ariad Pharmaceuticals, Inc. | Heterocycles and uses thereof |
WO2004060400A1 (en) * | 2003-01-06 | 2004-07-22 | Mitsubishi Pharma Corp | Antipsychotic molecular-targeting epithelial growth factor receptor |
WO2004069791A2 (en) * | 2003-02-05 | 2004-08-19 | Warner-Lambert Company Llc | Preparation of substituted quinazolines |
WO2004069791A3 (en) * | 2003-02-05 | 2004-12-16 | Warner Lambert Co | Preparation of substituted quinazolines |
US7223749B2 (en) | 2003-02-20 | 2007-05-29 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them |
US8937158B2 (en) | 2003-03-03 | 2015-01-20 | Xencor, Inc. | Fc variants with increased affinity for FcγRIIc |
US8034821B2 (en) | 2003-04-11 | 2011-10-11 | The Regents Of The University Of California | Selective serine/threonine kinase inhibitors |
US7687506B2 (en) | 2003-04-11 | 2010-03-30 | The Regents Of The University Of California | Selective serine/threonine kinase inhibitors |
US7659279B2 (en) | 2003-04-30 | 2010-02-09 | Astrazeneca Ab | Quinazoline derivatives and their use in the treatment of cancer |
EP3101030A1 (en) | 2003-05-02 | 2016-12-07 | Xencor, Inc. | Optimized fc variants and methods for their generation |
EP3838920A1 (en) | 2003-05-02 | 2021-06-23 | Xencor, Inc. | Optimized fc variants and methods for their generation |
EP2368911A1 (en) | 2003-05-02 | 2011-09-28 | Xencor Inc. | Optimized Fc variants and methods for their generation |
EP2042490A2 (en) | 2003-05-16 | 2009-04-01 | AstraZeneca AB | Benzimidazole derivatives as vanilloid receptor antagonists |
WO2004103306A2 (en) | 2003-05-19 | 2004-12-02 | Irm Llc | Immunosuppressant compounds and compositions |
EP3272736A1 (en) | 2003-05-19 | 2018-01-24 | Novartis Ag | Immunosuppressant compounds and compositions |
WO2005000833A1 (en) | 2003-05-19 | 2005-01-06 | Irm, Llc | Immunosuppressant compounds and compositions |
EP2514743A1 (en) | 2003-05-19 | 2012-10-24 | Irm Llc | Immunosuppressant Compounds and Compositions |
EP2644195A1 (en) | 2003-05-19 | 2013-10-02 | Irm Llc | Immunosuppressant Compounds and Compositions |
EP2348110A1 (en) | 2003-05-30 | 2011-07-27 | AstraZeneca UK Limited | Process |
US7989462B2 (en) | 2003-07-03 | 2011-08-02 | Myrexis, Inc. | 4-arylamin-or-4-heteroarylamino-quinazolines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
US8309562B2 (en) | 2003-07-03 | 2012-11-13 | Myrexis, Inc. | Compounds and therapeutical use thereof |
US7569577B2 (en) | 2003-09-16 | 2009-08-04 | Astrazeneca Ab | Quinazoline derivatives as tyrosine kinase inhibitors |
US7838530B2 (en) | 2003-09-25 | 2010-11-23 | Astrazeneca Ab | Quinazoline derivatives as antiproliferative agents |
US9714282B2 (en) | 2003-09-26 | 2017-07-25 | Xencor, Inc. | Optimized Fc variants and methods for their generation |
US7456189B2 (en) | 2003-09-30 | 2008-11-25 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation |
US8426586B2 (en) | 2003-10-17 | 2013-04-23 | Boehringer Ingelheim International Gmbh | Process for preparing amino crotonyl compounds |
EP2489364A1 (en) | 2003-11-06 | 2012-08-22 | Seattle Genetics, Inc. | Monomethylvaline compounds onjugated to antibodies |
EP3858387A1 (en) | 2003-11-06 | 2021-08-04 | Seagen Inc. | Monomethylvaline compounds capable of conjugation to ligands |
EP2478912A1 (en) | 2003-11-06 | 2012-07-25 | Seattle Genetics, Inc. | Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy |
EP3434275A1 (en) | 2003-11-06 | 2019-01-30 | Seattle Genetics, Inc. | Assay for cancer cells based on the use of auristatin conjugates with antibodies |
EP3120861A1 (en) | 2003-11-06 | 2017-01-25 | Seattle Genetics, Inc. | Intermediate for conjugate preparation comprising auristatin derivatives and a linker |
EP2486933A1 (en) | 2003-11-06 | 2012-08-15 | Seattle Genetics, Inc. | Monomethylvaline compounds conjugated with antibodies |
EP2260858A2 (en) | 2003-11-06 | 2010-12-15 | Seattle Genetics, Inc. | Monomethylvaline compounds capable of conjugation to ligands |
US7625908B2 (en) | 2003-11-13 | 2009-12-01 | Astrazeneca Ab | Quinazoline derivatives |
US8933067B2 (en) | 2003-12-18 | 2015-01-13 | Janssen Pharmaceutica Nv | Pyrido and pyrimidopyrimidine derivatives as anti-profilerative agents |
US8772272B2 (en) | 2003-12-18 | 2014-07-08 | Janssen Pharmaceutica Nv | Pyrido-and pyrimidopyrimidine derivatives as anti-proliferative agents |
US7632840B2 (en) | 2004-02-03 | 2009-12-15 | Astrazeneca Ab | Quinazoline compounds for the treatment of hyperproliferative disorders |
EP2439285A1 (en) | 2004-03-31 | 2012-04-11 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
EP2423331A2 (en) | 2004-03-31 | 2012-02-29 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
EP2439284A1 (en) | 2004-03-31 | 2012-04-11 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
EP3611273A1 (en) | 2004-03-31 | 2020-02-19 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
EP2447375A2 (en) | 2004-03-31 | 2012-05-02 | The General Hospital Corporation | Method to determine responsiveness of cancer to epidermal growth factor receptor targeting treatments |
EP2253614A1 (en) | 2004-04-07 | 2010-11-24 | Novartis AG | Inhibitors of IAP |
EP2065368A1 (en) | 2004-04-07 | 2009-06-03 | Novartis Ag | Inhibitors of IAP |
WO2005107758A1 (en) * | 2004-05-06 | 2005-11-17 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
EA011237B1 (en) * | 2004-05-06 | 2009-02-27 | УОРНЕР-ЛАМБЕРТ КОМПАНИ Эл-Эл-Си | 4-phenylamino-quinazolin-6-yl-amides |
US7772243B2 (en) | 2004-05-06 | 2010-08-10 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
US8466165B2 (en) | 2004-05-06 | 2013-06-18 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
US8623883B2 (en) | 2004-05-06 | 2014-01-07 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
AU2005239878B9 (en) * | 2004-05-06 | 2010-01-07 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
AU2005239878B2 (en) * | 2004-05-06 | 2009-09-03 | Warner-Lambert Company Llc | 4-phenylamino-quinazolin-6-yl-amides |
US8080577B2 (en) | 2004-05-06 | 2011-12-20 | Bioresponse, L.L.C. | Diindolylmethane formulations for the treatment of leiomyomas |
KR100885835B1 (en) * | 2004-05-06 | 2009-02-26 | 워너-램버트 캄파니 엘엘씨 | 4-phenylamino-quinazolin-6-yl-amides |
AP2204A (en) * | 2004-05-06 | 2011-02-07 | Warner Lambert Co | 4-phenylamino-quinazolin-6-yl-amides. |
EP2286844A2 (en) | 2004-06-01 | 2011-02-23 | Genentech, Inc. | Antibody-drug conjugates and methods |
US8178543B2 (en) | 2004-06-02 | 2012-05-15 | Takeda Pharmaceutical Company Limited | Bi- and tricyclic fused pyrimidines as tyrosine kinase inhibitors |
EP2418205A1 (en) | 2004-06-24 | 2012-02-15 | Novartis AG | Pyrimidine urea derivatives as kinase inhibitors |
EP2409969A1 (en) | 2004-06-24 | 2012-01-25 | Novartis AG | Pyrimidine urea derivatives as kinase inhibitors |
EP2471813A1 (en) | 2004-07-15 | 2012-07-04 | Xencor Inc. | Optimized Fc variants |
EP3342782A1 (en) | 2004-07-15 | 2018-07-04 | Xencor, Inc. | Optimized fc variants |
EP3088004A1 (en) | 2004-09-23 | 2016-11-02 | Genentech, Inc. | Cysteine engineered antibodies and conjugates |
EP3498294A1 (en) | 2004-10-20 | 2019-06-19 | Genentech, Inc. | Antibody formulations |
EP2371388A2 (en) | 2004-10-20 | 2011-10-05 | Genentech, Inc. | Antibody formulations |
US8883973B2 (en) | 2004-11-12 | 2014-11-11 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US11198739B2 (en) | 2004-11-12 | 2021-12-14 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US10336818B2 (en) | 2004-11-12 | 2019-07-02 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US8852586B2 (en) | 2004-11-12 | 2014-10-07 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US9200079B2 (en) | 2004-11-12 | 2015-12-01 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US9803023B2 (en) | 2004-11-12 | 2017-10-31 | Xencor, Inc. | Fc variants with altered binding to FcRn |
US10208062B2 (en) | 2004-12-08 | 2019-02-19 | Janssen Pharmaceutica Nv | Macrocyclic quinazole derivatives and their use as MTKI |
US9688691B2 (en) | 2004-12-08 | 2017-06-27 | Janssen Pharmaceutica Nv | Macrocyclic quinazole derivatives and their use as MTKI |
US7947676B2 (en) | 2004-12-14 | 2011-05-24 | Astrazeneca Ab | Pyrazolo[3,4-d]pyrimidine compounds as antitumor agents |
US8552052B2 (en) | 2004-12-30 | 2013-10-08 | Bioresponse, L.L.C. | Use of diindolylmethane-related indoles for the treatment and prevention of respiratory syncytial virus associated conditions |
WO2006083458A2 (en) | 2004-12-30 | 2006-08-10 | Bioresponse Llc | Use of diindolylmethane-related indoles for the treatment and prevention of respiratory syncytial virus associates conditions |
US7989486B2 (en) | 2004-12-30 | 2011-08-02 | Bioresponse, L.L.C. | Use of diindolylmethane-related indoles for the treatment and prevention of respiratory syncytial virus associated conditions |
US8258145B2 (en) | 2005-01-03 | 2012-09-04 | Myrexis, Inc. | Method of treating brain cancer |
EP3698807A1 (en) | 2005-01-21 | 2020-08-26 | Genentech, Inc. | Fixed dosing of her antibodies |
EP2399605A1 (en) | 2005-02-23 | 2011-12-28 | Genentech, Inc. | Extending time to disease progression or survival in cancer patients |
EP2270008A1 (en) | 2005-05-20 | 2011-01-05 | Novartis AG | 1,3-dihydro-imidazo[4,5-c]quinolin-2-ones as lipid kinase and/or pi3 kinases inhibitors |
EP2292617A1 (en) | 2005-05-20 | 2011-03-09 | Novartis AG | 1,3-dihydro-imidazo[4,5-c]quinolin-2-ones as lipid kinase and/or pi3 kinase inhibitors |
US7820683B2 (en) | 2005-09-20 | 2010-10-26 | Astrazeneca Ab | 4-(1H-indazol-5-yl-amino)-quinazoline compounds as erbB receptor tyrosine kinase inhibitors for the treatment of cancer |
US9040041B2 (en) | 2005-10-03 | 2015-05-26 | Xencor, Inc. | Modified FC molecules |
US9539258B2 (en) | 2005-11-11 | 2017-01-10 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
US9089571B2 (en) | 2005-11-11 | 2015-07-28 | Boehringer Ingelheim International Gmbh | Quinazoline derivatives for the treatment of cancer diseases |
EP2022498A2 (en) | 2005-11-21 | 2009-02-11 | Novartis AG | Neuroendocrine tumour treatment |
EP2275103A2 (en) | 2005-11-21 | 2011-01-19 | Novartis AG | mTOR inhibitors in the treatment of endocrine tumors |
EP1990337A4 (en) * | 2006-01-20 | 2009-07-22 | Shanghai Allist Pharmaceutical | Quinazoline derivatives,preparation methods and uses thereof |
US8309563B2 (en) | 2006-01-20 | 2012-11-13 | Shanghai Allist Pharmaceuticals, Inc. | Quinazoline derivatives useful as anti-tumor medicament |
US8044063B2 (en) | 2006-01-20 | 2011-10-25 | Shanghai Allist Pharmaceuticals, Inc. | Quinazoline derivatives useful as anti-tumor medicament |
EP1990337A1 (en) * | 2006-01-20 | 2008-11-12 | Shanghai Allist Pharmaceutical., Inc. | Quinazoline derivatives,preparation methods and uses thereof |
WO2007082434A1 (en) | 2006-01-20 | 2007-07-26 | Shanghai Allist Pharmaceutical., Inc. | Quinazoline derivatives,preparation methods and uses thereof |
EP2248806A2 (en) | 2006-01-20 | 2010-11-10 | Shanghai Allist Pharmaceuticals, Inc. | Quinazoline derivatives as tyrosine kinase inhibitors |
EP2371822A1 (en) | 2006-03-14 | 2011-10-05 | Novartis AG | Heterobicyclic carboxamides as inhibitors for kinases |
EP2591775A1 (en) | 2006-04-05 | 2013-05-15 | Novartis AG | Combinations comprising mtor inhibitors for treating cancer |
EP2314297A1 (en) | 2006-04-05 | 2011-04-27 | Novartis AG | Combinations comprising bcr-abl/c-kit/pdgf-r tk inhibitors for treating cancer |
EP2272511A1 (en) | 2006-05-09 | 2011-01-12 | Novartis AG | Combination comprising an iron chelator and an anti-neoplastic agent and use thereof |
US8492377B2 (en) | 2006-07-13 | 2013-07-23 | Janssen Pharmaceutica Nv | MTKI quinazoline derivatives |
EP2383297A1 (en) | 2006-08-14 | 2011-11-02 | Xencor Inc. | Optimized antibodies that target CD19 |
EP2845912A1 (en) | 2006-09-12 | 2015-03-11 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using KIT gene as genetic marker |
EP2386655A2 (en) | 2006-09-12 | 2011-11-16 | Genentech, Inc. | Methods and compositions for the diagnosis and treatment of lung cancer using KIT or KDG gene as genetic marker |
US8877764B2 (en) | 2006-09-18 | 2014-11-04 | Boehringer Ingelheim International Gmbh | Method for treating cancer harboring EGFR mutations |
WO2008037477A1 (en) | 2006-09-29 | 2008-04-03 | Novartis Ag | Pyrazolopyrimidines as p13k lipid kinase inhibitors |
US8586621B2 (en) | 2006-10-27 | 2013-11-19 | Michael A. Zeligs | Anti-parasitic methods and compositions utilizing diindolylmethane-related indoles |
US9663462B2 (en) | 2006-10-27 | 2017-05-30 | Bioresponse, L.L.C. | Anti-parasitic methods and compositions utilizing diindolylmethane-related indoles |
US9353058B2 (en) | 2006-10-27 | 2016-05-31 | Bioresponse, L.L.C. | Anti-parasitic methods and compositions utilizing diindolylmethane-related indoles |
US8399461B2 (en) | 2006-11-10 | 2013-03-19 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, medicaments containing said compounds, use thereof, and method for production of same |
US7998949B2 (en) | 2007-02-06 | 2011-08-16 | Boehringer Ingelheim International Gmbh | Bicyclic heterocycles, drugs containing said compounds, use thereof, and method for production thereof |
WO2008098485A1 (en) | 2007-02-14 | 2008-08-21 | Shanghai Allist Pharmaceuticals, Inc. | The salts of 4-aniline quinazoline derivative |
US8349854B2 (en) | 2007-02-14 | 2013-01-08 | Shanghai Allist Pharmaceuticals, Inc. | Salts of 4-aniline quinazoline derivative |
EP2491923A2 (en) | 2007-02-15 | 2012-08-29 | Novartis AG | Combinations of therapeutic agents for treating cancer |
EP2359818A1 (en) | 2007-02-15 | 2011-08-24 | Novartis AG | Combination of LBH589 with HSP 90 inhibitors for treating cancer |
US8940302B2 (en) | 2007-03-02 | 2015-01-27 | Genentech, Inc. | Predicting response to a HER inhibitor |
US7981418B2 (en) | 2007-03-02 | 2011-07-19 | Genentech, Inc. | Predicting response to a HER inhibitor |
EP2899541A1 (en) | 2007-03-02 | 2015-07-29 | Genentech, Inc. | Predicting response to a HER dimerisation inhbitor based on low HER3 expression |
US9394366B2 (en) | 2007-05-30 | 2016-07-19 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
US9079960B2 (en) | 2007-05-30 | 2015-07-14 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
EP2708557A1 (en) | 2007-05-30 | 2014-03-19 | Xencor, Inc. | Method and compositions for inhibiting CD32B expressing cells |
US11434295B2 (en) | 2007-05-30 | 2022-09-06 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
US9902773B2 (en) | 2007-05-30 | 2018-02-27 | Xencor, Inc. | Methods and compositions for inhibiting CD32b expressing cells |
US8063187B2 (en) | 2007-05-30 | 2011-11-22 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
US9914778B2 (en) | 2007-05-30 | 2018-03-13 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
US11447552B2 (en) | 2007-05-30 | 2022-09-20 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells |
US9260523B2 (en) | 2007-05-30 | 2016-02-16 | Xencor, Inc. | Methods and compositions for inhibiting CD32b expressing cells |
EP2592156A2 (en) | 2007-06-08 | 2013-05-15 | Genentech, Inc. | Gene expression markers of tumor resistance to HER2 inhibitor treatment |
US8318731B2 (en) | 2007-07-27 | 2012-11-27 | Janssen Pharmaceutica Nv | Pyrrolopyrimidines |
WO2009030224A2 (en) * | 2007-09-07 | 2009-03-12 | Schebo Biotech Ag | Novel quinazoline compounds and the use thereof for treating cancerous diseases |
WO2009030224A3 (en) * | 2007-09-07 | 2009-08-13 | Schebo Biotech Ag | Novel quinazoline compounds and the use thereof for treating cancerous diseases |
US8080558B2 (en) | 2007-10-29 | 2011-12-20 | Natco Pharma Limited | 4-(tetrazol-5-yl)-quinazoline derivatives as anti-cancer agent |
US11932685B2 (en) | 2007-10-31 | 2024-03-19 | Xencor, Inc. | Fc variants with altered binding to FcRn |
EP4119583A1 (en) | 2008-01-30 | 2023-01-18 | Genentech, Inc. | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
EP3401335A1 (en) | 2008-01-30 | 2018-11-14 | Genentech, Inc. | Composition comprising antibody that binds to domain ii of her2 and acidic variants thereof |
US8772298B2 (en) | 2008-02-07 | 2014-07-08 | Boehringer Ingelheim International Gmbh | Spirocyclic heterocycles medicaments containing said compounds, use thereof and method for their production |
US8497369B2 (en) | 2008-02-07 | 2013-07-30 | Boehringer Ingelheim International Gmbh | Spirocyclic heterocycles medicaments containing said compounds, use thereof and method for their production |
WO2009118292A1 (en) | 2008-03-24 | 2009-10-01 | Novartis Ag | Arylsulfonamide-based matrix metalloprotease inhibitors |
EP2628726A1 (en) | 2008-03-26 | 2013-08-21 | Novartis AG | Hydroxamate-based inhibitors of deacetylases b |
US8088782B2 (en) | 2008-05-13 | 2012-01-03 | Astrazeneca Ab | Crystalline 4-(3-chloro-2-fluoroanilino)-7 methoxy-6-{[1-(N-methylcarbamoylmethyl)piperidin-4-yl]oxy}quinazoline difumarate form A |
EP2615183A1 (en) | 2008-05-14 | 2013-07-17 | Genomic Health, Inc. | Predictors of patient response to treatment with EGF receptor inhibitors |
WO2009140863A1 (en) | 2008-05-21 | 2009-11-26 | 上海艾力斯医药科技有限公司 | Compositions comprising quinazoline derivatives, preparation methods and uses thereof |
US8507010B2 (en) | 2008-05-21 | 2013-08-13 | Shanghai Allist Pharmaceuticals, Inc. | Compositions comprising quinazoline derivatives |
US8648191B2 (en) | 2008-08-08 | 2014-02-11 | Boehringer Ingelheim International Gmbh | Cyclohexyloxy substituted heterocycles, pharmaceutical compositions containing these compounds and processes for preparing them |
WO2010043050A1 (en) | 2008-10-16 | 2010-04-22 | Celator Pharmaceuticals Corporation | Combinations of a liposomal water-soluble camptothecin with cetuximab or bevacizumab |
US8710104B2 (en) | 2008-11-07 | 2014-04-29 | Triact Therapeutics, Inc. | Catecholic butanes and use thereof for cancer therapy |
US8507502B2 (en) | 2008-11-10 | 2013-08-13 | National Health Research Institutes | Fused bicyclic and tricyclic pyrimidine compounds as tyrosine kinase inhibitors |
WO2010080409A1 (en) | 2008-12-18 | 2010-07-15 | Novartis Ag | Hemifumarate salt of 1- [4- [1- ( 4 -cyclohexyl-3 -trifluoromethyl-benzyloxyimino ) -ethyl] -2 -ethyl-benzyl] -a zetidine-3-carboxylic acid |
WO2010080455A1 (en) | 2008-12-18 | 2010-07-15 | Novartis Ag | New salts |
WO2010071794A1 (en) | 2008-12-18 | 2010-06-24 | Novartis Ag | New polymorphic form of 1- (4- { l- [ (e) -4-cyclohexyl--3-trifluoromethyl-benzyloxyimino] -ethyl) -2-ethyl-benzy l) -azetidine-3-carboxylic |
ITMI20082336A1 (en) * | 2008-12-29 | 2010-06-30 | Univ Parma | COMPOUNDS IRREVERSIBLE EGFR INHIBITORS WITH ANTI-PROLIFERATIVE ACTIVITY |
WO2010083617A1 (en) | 2009-01-21 | 2010-07-29 | Oncalis Ag | Pyrazolopyrimidines as protein kinase inhibitors |
WO2010088335A1 (en) | 2009-01-29 | 2010-08-05 | Novartis Ag | Substituted benzimidazoles for the treatment of astrocytomas |
WO2010099139A2 (en) | 2009-02-25 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Combination anti-cancer therapy |
WO2010099137A2 (en) | 2009-02-26 | 2010-09-02 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the emt status of tumor cells in vivo |
WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099364A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
WO2010099363A1 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
US9073916B2 (en) | 2009-03-11 | 2015-07-07 | Auckland Uniservices Limited | Prodrug forms of kinase inhibitors and their use in therapy |
WO2010107968A1 (en) | 2009-03-18 | 2010-09-23 | Osi Pharmaceuticals, Inc. | Combination cancer therapy comprising administration of an egfr inhibitor and an igf-1r inhibitor |
WO2010149755A1 (en) | 2009-06-26 | 2010-12-29 | Novartis Ag | 1, 3-disubstituted imidazolidin-2-one derivatives as inhibitors of cyp 17 |
US10004743B2 (en) | 2009-07-06 | 2018-06-26 | Boehringer Ingelheim International Gmbh | Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
US9545381B2 (en) | 2009-07-06 | 2017-01-17 | Boehringer Ingelheim International Gmbh | Process for drying of BIBW2992, of its salts and of solid pharmaceutical formulations comprising this active ingredient |
EP2687202A1 (en) | 2009-07-31 | 2014-01-22 | F. Hoffmann-La Roche AG | Subcutaneous anti-her2 antibody formulation |
WO2011012637A2 (en) | 2009-07-31 | 2011-02-03 | F. Hoffmann-La Roche Ag | Subcutaneous anti-her2 antibody formulation |
EP4339212A2 (en) | 2009-07-31 | 2024-03-20 | F. Hoffmann-La Roche AG | Subcutaneous anti-her2 antibody formulation |
WO2011015652A1 (en) | 2009-08-07 | 2011-02-10 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives as c-met tyrosine kinase modulators |
WO2011018454A1 (en) | 2009-08-12 | 2011-02-17 | Novartis Ag | Heterocyclic hydrazone compounds and their uses to treat cancer and inflammation |
WO2011022439A1 (en) | 2009-08-17 | 2011-02-24 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
WO2011020861A1 (en) | 2009-08-20 | 2011-02-24 | Novartis Ag | Heterocyclic oxime compounds |
WO2011023677A1 (en) | 2009-08-26 | 2011-03-03 | Novartis Ag | Tetra-substituted heteroaryl compounds and their use as mdm2 and/or mdm4 modulators |
CN102574846A (en) * | 2009-09-02 | 2012-07-11 | 奥克兰联合服务有限公司 | Kinase inhibitors, prodrug forms thereof and their use in therapy |
US11401348B2 (en) | 2009-09-02 | 2022-08-02 | Xencor, Inc. | Heterodimeric Fc variants |
AU2010290199B2 (en) * | 2009-09-02 | 2016-10-27 | Auckland Uniservices Limited | Kinase inhibitors, prodrug forms thereof and their use in therapy |
CN102574846B (en) * | 2009-09-02 | 2014-12-03 | 奥克兰联合服务有限公司 | Kinase inhibitors, prodrug forms thereof and their use in therapy |
US9101632B2 (en) | 2009-09-02 | 2015-08-11 | Auckland Uniservices Limited | Kinase inhibitors, prodrug forms thereof and their use in therapy |
RU2568639C2 (en) * | 2009-09-02 | 2015-11-20 | Окленд Юнисервисиз Лимитед | Kinase inhibitors, prodrug forms thereof and use thereof in therapy |
WO2011028135A1 (en) | 2009-09-02 | 2011-03-10 | Auckland Uniservices Limited | Kinase inhibitors, prodrug forms thereof and their use in therapy |
WO2011029915A1 (en) | 2009-09-10 | 2011-03-17 | Novartis Ag | Ether derivatives of bicyclic heteroaryls |
US9556426B2 (en) | 2009-09-16 | 2017-01-31 | Celgene Avilomics Research, Inc. | Protein kinase conjugates and inhibitors |
US10662195B2 (en) | 2009-09-16 | 2020-05-26 | Celgene Car Llc | Protein kinase conjugates and inhibitors |
WO2011054828A1 (en) | 2009-11-04 | 2011-05-12 | Novartis Ag | Heterocyclic sulfonamide derivatives useful as mek inhibitors |
WO2011058164A1 (en) | 2009-11-13 | 2011-05-19 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
WO2011063421A1 (en) | 2009-11-23 | 2011-05-26 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
WO2011064211A1 (en) | 2009-11-25 | 2011-06-03 | Novartis Ag | Benzene-fused 6-membered oxygen-containing heterocyclic derivatives of bicyclic heteroaryls |
US10584181B2 (en) | 2009-12-04 | 2020-03-10 | Genentech, Inc. | Methods of making and using multispecific antibody panels and antibody analog panels |
EP3778917A2 (en) | 2009-12-04 | 2021-02-17 | F. Hoffmann-La Roche AG | Multispecific antibodies, antibody analogs, compositions, and methods |
WO2011070030A1 (en) | 2009-12-08 | 2011-06-16 | Novartis Ag | Heterocyclic sulfonamide derivatives |
WO2011076786A1 (en) | 2009-12-22 | 2011-06-30 | Novartis Ag | Substituted isoquinolinones and quinazolinones |
US11542492B2 (en) | 2009-12-30 | 2023-01-03 | Celgene Car Llc | Ligand-directed covalent modification of protein |
WO2011086053A1 (en) | 2010-01-12 | 2011-07-21 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof |
WO2011090940A1 (en) | 2010-01-19 | 2011-07-28 | Cerulean Pharma Inc. | Cyclodextrin-based polymers for therapeutic delivery |
WO2011107664A1 (en) | 2010-03-04 | 2011-09-09 | Hospital District Of Southwest Finland | Method for selecting patients for treatment with an egfr inhibitor |
WO2011113802A2 (en) | 2010-03-17 | 2011-09-22 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
WO2011119995A2 (en) | 2010-03-26 | 2011-09-29 | Cerulean Pharma Inc. | Formulations and methods of use |
EP3208281A1 (en) | 2010-03-29 | 2017-08-23 | Zymeworks, Inc. | Antibodies with enhanced or suppressed effector function |
WO2011130654A1 (en) | 2010-04-16 | 2011-10-20 | Genentech, Inc. | Fox03a as predictive biomarker for pi3k/akt kinase pathway inhibitor efficacy |
WO2011146568A1 (en) | 2010-05-19 | 2011-11-24 | Genentech, Inc. | Predicting response to a her inhibitor |
WO2011157787A1 (en) | 2010-06-17 | 2011-12-22 | Novartis Ag | Biphenyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
WO2011157793A1 (en) | 2010-06-17 | 2011-12-22 | Novartis Ag | Piperidinyl substituted 1,3-dihydro-benzoimidazol-2-ylideneamine derivatives |
WO2012004299A1 (en) | 2010-07-06 | 2012-01-12 | Novartis Ag | Tetrahydro-pyrido-pyrimidine derivatives |
US9730934B2 (en) | 2010-08-30 | 2017-08-15 | Xuanzhu Pharma Co., Ltd. | Quinazoline derivatives substituted by aniline, preparation method and use thereof |
WO2012027960A1 (en) | 2010-08-30 | 2012-03-08 | 山东轩竹医药科技有限公司 | Quinazoline derivatives substituted by aniline, preparation method and use thereof |
US10507209B2 (en) | 2010-08-30 | 2019-12-17 | Xuanzhu Pharma Co, Ltd. | Quinazoline derivatives substituted by aniline, preparation method and use thereof |
WO2012035039A1 (en) | 2010-09-15 | 2012-03-22 | F. Hoffmann-La Roche Ag | Azabenzothiazole compounds, compositions and methods of use |
WO2012035078A1 (en) | 2010-09-16 | 2012-03-22 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
WO2012065161A2 (en) | 2010-11-12 | 2012-05-18 | Scott & White Healthcare | Antibodies to tumor endothelial marker 8 |
WO2012066061A1 (en) | 2010-11-19 | 2012-05-24 | F. Hoffmann-La Roche Ag | Pyrazolopyridines and pyrazolopyridines and their use as tyk2 inhibitors |
WO2012066095A1 (en) | 2010-11-19 | 2012-05-24 | Novartis Ag | Crystalline form of an inhibitor of mdm2/4 and p53 interaction |
WO2012085815A1 (en) | 2010-12-21 | 2012-06-28 | Novartis Ag | Bi-heteroaryl compounds as vps34 inhibitors |
WO2012085229A1 (en) | 2010-12-22 | 2012-06-28 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
EP2468883A1 (en) | 2010-12-22 | 2012-06-27 | Pangaea Biotech S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
WO2012085176A1 (en) | 2010-12-23 | 2012-06-28 | F. Hoffmann-La Roche Ag | Tricyclic pyrazinone compounds, compositions and methods of use thereof as janus kinase inhibitors |
US9494572B2 (en) | 2011-01-11 | 2016-11-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
US9134297B2 (en) | 2011-01-11 | 2015-09-15 | Icahn School Of Medicine At Mount Sinai | Method and compositions for treating cancer and related methods |
WO2012107500A1 (en) | 2011-02-10 | 2012-08-16 | Novartis Ag | [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
EP2492688A1 (en) | 2011-02-23 | 2012-08-29 | Pangaea Biotech, S.A. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
WO2012113819A1 (en) | 2011-02-23 | 2012-08-30 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting response to antitumor treatment in lung cancer |
US9127000B2 (en) | 2011-02-23 | 2015-09-08 | Intellikine, LLC. | Heterocyclic compounds and uses thereof |
WO2012120469A1 (en) | 2011-03-08 | 2012-09-13 | Novartis Ag | Fluorophenyl bicyclic heteroaryl compounds |
WO2012122513A2 (en) | 2011-03-10 | 2012-09-13 | Omeros Corporation | Generation of anti-fn14 monoclonal antibodies by ex-vivo accelerated antibody evolution |
WO2012129145A1 (en) | 2011-03-18 | 2012-09-27 | OSI Pharmaceuticals, LLC | Nscle combination therapy |
WO2012149014A1 (en) | 2011-04-25 | 2012-11-01 | OSI Pharmaceuticals, LLC | Use of emt gene signatures in cancer drug discovery, diagnostics, and treatment |
WO2012149413A1 (en) | 2011-04-28 | 2012-11-01 | Novartis Ag | 17α-HYDROXYLASE/C17,20-LYASE INHIBITORS |
WO2012159457A1 (en) | 2011-05-26 | 2012-11-29 | 山东亨利医药科技有限责任公司 | Quinazoline derivative as tyrosine-kinase inhibitor, preparation method therefor and application thereof |
WO2012168884A1 (en) | 2011-06-09 | 2012-12-13 | Novartis Ag | Heterocyclic sulfonamide derivatives |
WO2012175487A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Cyclohexyl isoquinolinone compounds |
WO2012175520A1 (en) | 2011-06-20 | 2012-12-27 | Novartis Ag | Hydroxy substituted isoquinolinone derivatives |
WO2013001445A1 (en) | 2011-06-27 | 2013-01-03 | Novartis Ag | Solid forms and salts of tetrahydro-pyrido-pyrimidine derivatives |
WO2013007765A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Fused tricyclic compounds for use as inhibitors of janus kinases |
WO2013007768A1 (en) | 2011-07-13 | 2013-01-17 | F. Hoffmann-La Roche Ag | Tricyclic heterocyclic compounds, compositions and methods of use thereof as jak inhibitors |
WO2013020024A3 (en) * | 2011-08-03 | 2013-06-13 | Karyopharm Therapeutics, Inc. | Maleimide compounds and methods of treatment |
EP3783028A1 (en) | 2011-08-12 | 2021-02-24 | Omeros Corporation | Anti-fzd10 monoclonal antibodies and methods for their use |
WO2013024011A1 (en) | 2011-08-12 | 2013-02-21 | F. Hoffmann-La Roche Ag | Indazole compounds, compositions and methods of use |
EP3392274A1 (en) | 2011-08-12 | 2018-10-24 | Omeros Corporation | Anti-fzd10 monoclonal antibodies and methods for their use |
WO2013033380A1 (en) | 2011-08-31 | 2013-03-07 | Genentech, Inc. | Diagnostic markers |
WO2013038362A1 (en) | 2011-09-15 | 2013-03-21 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
WO2013041539A1 (en) | 2011-09-20 | 2013-03-28 | F. Hoffmann-La Roche Ag | Imidazopyridine compounds, compositions and methods of use |
WO2013055530A1 (en) | 2011-09-30 | 2013-04-18 | Genentech, Inc. | Diagnostic methylation markers of epithelial or mesenchymal phenotype and response to egfr kinase inhibitor in tumours or tumour cells |
WO2013080141A1 (en) | 2011-11-29 | 2013-06-06 | Novartis Ag | Pyrazolopyrrolidine compounds |
US9408885B2 (en) | 2011-12-01 | 2016-08-09 | Vib Vzw | Combinations of therapeutic agents for treating melanoma |
WO2013093849A1 (en) | 2011-12-22 | 2013-06-27 | Novartis Ag | Dihydro-benzo-oxazine and dihydro-pyrido-oxazine derivatives |
WO2013093850A1 (en) | 2011-12-22 | 2013-06-27 | Novartis Ag | Quinoline derivatives |
WO2013096055A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013096059A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013096060A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
US9585850B2 (en) | 2011-12-23 | 2017-03-07 | Duke University | Methods of treatment using arylcyclopropylamine compounds |
WO2013096051A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
WO2013096049A1 (en) | 2011-12-23 | 2013-06-27 | Novartis Ag | Compounds for inhibiting the interaction of bcl2 with binding partners |
EP3064502A1 (en) | 2012-01-26 | 2016-09-07 | Novartis AG | Imidazopyrrolidinone compounds |
EP3272754A1 (en) | 2012-01-26 | 2018-01-24 | Novartis AG | Imidazopyrrolidinone compounds |
WO2013134743A1 (en) | 2012-03-08 | 2013-09-12 | Halozyme, Inc. | Conditionally active anti-epidermal growth factor receptor antibodies and methods of use thereof |
EP3296320A1 (en) | 2012-03-08 | 2018-03-21 | Halozyme, Inc. | Conditionally active anti-epidermal growth factor receptor antibodies and methods of use thereof |
WO2013148315A1 (en) | 2012-03-27 | 2013-10-03 | Genentech, Inc. | Diagnosis and treatments relating to her3 inhibitors |
EP3964513A1 (en) | 2012-04-03 | 2022-03-09 | Novartis AG | Combination products with tyrosine kinase inhibitors and their use |
WO2013149581A1 (en) | 2012-04-03 | 2013-10-10 | Novartis Ag | Combination products with tyrosine kinase inhibitors and their use |
WO2013152252A1 (en) | 2012-04-06 | 2013-10-10 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
WO2013175417A1 (en) | 2012-05-24 | 2013-11-28 | Novartis Ag | Pyrrolopyrrolidinone compounds |
WO2013188763A1 (en) | 2012-06-15 | 2013-12-19 | The Brigham And Women's Hospital, Inc. | Compositions for treating cancer and methods for making the same |
WO2013190089A1 (en) | 2012-06-21 | 2013-12-27 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting outcome in lung cancer |
US10112947B2 (en) | 2012-08-06 | 2018-10-30 | Duke University | Substituted 6-aminopurines for targeting HSP90 |
US9738643B2 (en) | 2012-08-06 | 2017-08-22 | Duke University | Substituted indazoles for targeting Hsp90 |
US10927115B2 (en) | 2012-08-06 | 2021-02-23 | Duke University | Substituted heterocycles for targeting Hsp90 |
US10442806B2 (en) | 2012-08-06 | 2019-10-15 | Duke University | Substituted heterocycles for targeting HSP90 |
EP3919069A1 (en) | 2012-11-05 | 2021-12-08 | Dana-Farber Cancer Institute, Inc. | Xbp1, cd138, and cs1 peptides, pharmaceutical compositions that include the peptides, and methods of using such peptides and compositions |
WO2014071402A1 (en) | 2012-11-05 | 2014-05-08 | Dana-Farber Cancer Institute, Inc. | Xbp1, cd138, and cs1, pharmaceutical compositions that include the peptides, and methods of using such petides and compositions |
WO2014102630A1 (en) | 2012-11-26 | 2014-07-03 | Novartis Ag | Solid form of dihydro-pyrido-oxazine derivative |
WO2014115080A1 (en) | 2013-01-22 | 2014-07-31 | Novartis Ag | Pyrazolo[3,4-d]pyrimidinone compounds as inhibitors of the p53/mdm2 interaction |
WO2014115077A1 (en) | 2013-01-22 | 2014-07-31 | Novartis Ag | Substituted purinone compounds |
WO2014130657A1 (en) | 2013-02-20 | 2014-08-28 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
WO2014128612A1 (en) | 2013-02-20 | 2014-08-28 | Novartis Ag | Quinazolin-4-one derivatives |
EP3626741A1 (en) | 2013-02-20 | 2020-03-25 | The Trustees Of The University Of Pennsylvania | Treatment of cancer using humanized anti-egfrviii chimeric antigen receptor |
US9834575B2 (en) | 2013-02-26 | 2017-12-05 | Triact Therapeutics, Inc. | Cancer therapy |
WO2014139326A1 (en) | 2013-03-13 | 2014-09-18 | Genentech, Inc. | Pyrazolo compounds and uses thereof |
US11905298B2 (en) | 2013-03-14 | 2024-02-20 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11083703B2 (en) | 2013-03-14 | 2021-08-10 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US10406133B2 (en) | 2013-03-14 | 2019-09-10 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US9505776B2 (en) | 2013-03-14 | 2016-11-29 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11230548B2 (en) | 2013-03-14 | 2022-01-25 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US9090558B2 (en) | 2013-03-14 | 2015-07-28 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US10596140B2 (en) | 2013-03-14 | 2020-03-24 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US8669281B1 (en) | 2013-03-14 | 2014-03-11 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
US11679092B2 (en) | 2013-03-14 | 2023-06-20 | Alkermes Pharma Ireland Limited | Prodrugs of fumarates and their use in treating various diseases |
WO2014151147A1 (en) | 2013-03-15 | 2014-09-25 | Intellikine, Llc | Combination of kinase inhibitors and uses thereof |
WO2014147246A1 (en) | 2013-03-21 | 2014-09-25 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Method and pharmaceutical composition for use in the treatment of chronic liver diseases associated with a low hepcidin expression |
WO2014155268A2 (en) | 2013-03-25 | 2014-10-02 | Novartis Ag | Fgf-r tyrosine kinase activity inhibitors - use in diseases associated with lack of or reduced snf5 activity |
WO2014184778A1 (en) | 2013-05-17 | 2014-11-20 | Novartis Ag | Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof |
WO2015010641A1 (en) | 2013-07-24 | 2015-01-29 | Novartis Ag | Substituted quinazolin-4-one derivatives |
WO2015022662A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
WO2015022664A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
WO2015022663A1 (en) | 2013-08-14 | 2015-02-19 | Novartis Ag | Compounds and compositions as inhibitors of mek |
WO2015035062A1 (en) | 2013-09-05 | 2015-03-12 | Genentech, Inc. | Antiproliferative compounds |
US9381246B2 (en) | 2013-09-09 | 2016-07-05 | Triact Therapeutics, Inc. | Cancer therapy |
WO2015038984A2 (en) | 2013-09-12 | 2015-03-19 | Halozyme, Inc. | Modified anti-epidermal growth factor receptor antibodies and methods of use thereof |
WO2015042078A2 (en) | 2013-09-22 | 2015-03-26 | Calitor Sciences, Llc | Substituted aminopyrimidine compounds and methods of use |
WO2015042077A1 (en) | 2013-09-22 | 2015-03-26 | Calitor Sciences, Llc | Substituted aminopyrimidine compounds and methods of use |
WO2015049325A1 (en) | 2013-10-03 | 2015-04-09 | F. Hoffmann-La Roche Ag | Therapeutic inhibitors of cdk8 and uses thereof |
WO2015084804A1 (en) | 2013-12-03 | 2015-06-11 | Novartis Ag | Combination of mdm2 inhibitor and braf inhibitor and their use |
EP3527587A1 (en) | 2013-12-17 | 2019-08-21 | F. Hoffmann-La Roche AG | Combination therapy comprising ox40 binding agonists and pd-l1 binding antagonists |
EP3680254A1 (en) | 2013-12-17 | 2020-07-15 | F. Hoffmann-La Roche AG | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
WO2015095423A2 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
WO2015095418A1 (en) | 2013-12-17 | 2015-06-25 | Genentech, Inc. | Methods of treating her2-positive cancers using pd-1 axis binding antagonists and anti-her2 antibodies |
EP3647324A1 (en) | 2013-12-17 | 2020-05-06 | F. Hoffmann-La Roche AG | Methods of treating cancers using pd-1 axis binding antagonists and taxanes |
US9242965B2 (en) | 2013-12-31 | 2016-01-26 | Boehringer Ingelheim International Gmbh | Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors |
US9604922B2 (en) | 2014-02-24 | 2017-03-28 | Alkermes Pharma Ireland Limited | Sulfonamide and sulfinamide prodrugs of fumarates and their use in treating various diseases |
US10000469B2 (en) | 2014-03-25 | 2018-06-19 | Duke University | Heat shock protein 70 (hsp-70) receptor ligands |
WO2015145388A2 (en) | 2014-03-27 | 2015-10-01 | Novartis Ag | Methods of treating colorectal cancers harboring upstream wnt pathway mutations |
EP3312164A1 (en) | 2014-03-28 | 2018-04-25 | Calitor Sciences, LLC | Substituted heteroaryl compounds and methods of use |
EP3327006A1 (en) | 2014-03-28 | 2018-05-30 | Calitor Sciences, LLC | Substituted heteroaryl compounds and methods of use |
WO2015153513A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Anti-ox40 antibodies and methods of use |
US9975957B2 (en) | 2014-03-31 | 2018-05-22 | Genentech, Inc. | Anti-OX40 antibodies and methods of use |
EP3632934A1 (en) | 2014-03-31 | 2020-04-08 | F. Hoffmann-La Roche AG | Anti-ox40 antibodies and methods of use |
WO2015153514A1 (en) | 2014-03-31 | 2015-10-08 | Genentech, Inc. | Combination therapy comprising anti-angiogenesis agents and ox40 binding agonists |
US10730951B2 (en) | 2014-03-31 | 2020-08-04 | Genentech, Inc. | Anti-OX40 antibodies and methods of use |
US10426753B2 (en) | 2014-04-03 | 2019-10-01 | Invictus Oncology Pvt. Ltd. | Supramolecular combinatorial therapeutics |
WO2015156674A2 (en) | 2014-04-10 | 2015-10-15 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
WO2016011956A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
WO2016016822A1 (en) | 2014-07-31 | 2016-02-04 | Novartis Ag | Combination therapy |
US10196365B2 (en) | 2014-08-15 | 2019-02-05 | Arromax Pharmatech Co., Ltd. | Quinazoline derivative, preparation method therefor, and pharmaceutical composition and application thereof |
WO2016036873A1 (en) | 2014-09-05 | 2016-03-10 | Genentech, Inc. | Therapeutic compounds and uses thereof |
WO2016044694A1 (en) | 2014-09-19 | 2016-03-24 | Genentech, Inc. | Use of cbp/ep300 and bet inhibitors for treatment of cancer |
WO2016057924A1 (en) | 2014-10-10 | 2016-04-14 | Genentech, Inc. | Pyrrolidine amide compounds as histone demethylase inhibitors |
US10845364B2 (en) | 2014-11-03 | 2020-11-24 | Genentech, Inc. | Assays for detecting T cell immune subsets and methods of use thereof |
WO2016073378A1 (en) | 2014-11-03 | 2016-05-12 | Genentech, Inc. | Assays for detecting t cell immune subsets and methods of use thereof |
US10767232B2 (en) | 2014-11-03 | 2020-09-08 | Genentech, Inc. | Methods and biomarkers for predicting efficacy and evaluation of an OX40 agonist treatment |
WO2016073282A1 (en) | 2014-11-06 | 2016-05-12 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and tigit inhibitors |
WO2016077375A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Bromodomain inhibitors and uses thereof |
WO2016077380A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Substituted pyrrolopyridines as inhibitors of bromodomain |
WO2016077378A1 (en) | 2014-11-10 | 2016-05-19 | Genentech, Inc. | Substituted pyrrolopyrdines as inhibitors of bromodomain |
WO2016081384A1 (en) | 2014-11-17 | 2016-05-26 | Genentech, Inc. | Combination therapy comprising ox40 binding agonists and pd-1 axis binding antagonists |
WO2016086200A1 (en) | 2014-11-27 | 2016-06-02 | Genentech, Inc. | 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
EP3632915A1 (en) | 2014-11-27 | 2020-04-08 | Genentech, Inc. | 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
WO2016106340A2 (en) | 2014-12-23 | 2016-06-30 | Genentech, Inc. | Compositions and methods for treating and diagnosing chemotherapy-resistant cancers |
EP3699290A1 (en) | 2014-12-24 | 2020-08-26 | F. Hoffmann-La Roche AG | Therapeutic, diagnostic, and prognostic methods for cancer |
WO2016109546A2 (en) | 2014-12-30 | 2016-07-07 | Genentech, Inc. | Methods and compositions for prognosis and treatment of cancers |
WO2016112298A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | Pyridazinone derivatives and their use in the treatment of cancer |
WO2016112284A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | (piperidin-3-yl)(naphthalen-2-yl)methanone derivatives and related compounds as inhibitors of the histone demethylase kdm2b for the treatment of cancer |
WO2016112251A1 (en) | 2015-01-09 | 2016-07-14 | Genentech, Inc. | 4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors |
WO2016123391A1 (en) | 2015-01-29 | 2016-08-04 | Genentech, Inc. | Therapeutic compounds and uses thereof |
WO2016123387A1 (en) | 2015-01-30 | 2016-08-04 | Genentech, Inc. | Therapeutic compounds and uses thereof |
WO2016138114A1 (en) | 2015-02-25 | 2016-09-01 | Genentech, Inc. | Therapeutic pyridazine compounds and uses thereof |
WO2016164480A1 (en) | 2015-04-07 | 2016-10-13 | Genentech, Inc. | Antigen binding complex having agonistic activity and methods of use |
US10865248B2 (en) | 2015-04-07 | 2020-12-15 | Genentech, Inc. | Antigen binding complex having agonistic activity and methods of use |
EP3783029A1 (en) | 2015-05-12 | 2021-02-24 | F. Hoffmann-La Roche AG | Therapeutic and diagnostic methods for cancer |
EP3708681A1 (en) | 2015-05-29 | 2020-09-16 | F. Hoffmann-La Roche AG | Therapeutic and diagnostic methods for cancer |
WO2016196298A1 (en) | 2015-05-29 | 2016-12-08 | Genentech, Inc. | Therapeutic and diagnolstic methods for cancer |
EP4335931A2 (en) | 2015-05-29 | 2024-03-13 | F. Hoffmann-La Roche AG | Therapeutic and diagnostic methods for cancer |
WO2016200836A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies |
WO2016200835A1 (en) | 2015-06-08 | 2016-12-15 | Genentech, Inc. | Methods of treating cancer using anti-ox40 antibodies and pd-1 axis binding antagonists |
WO2016205320A1 (en) | 2015-06-17 | 2016-12-22 | Genentech, Inc. | Methods of treating locally advanced or metastatic breast cancers using pd-1 axis binding antagonists and taxanes |
WO2017033019A1 (en) | 2015-08-26 | 2017-03-02 | Fundación Centro Nacional De Investigaciones Oncológicas Carlos Iii (Cnio) | Condensed tricyclic compounds as protein kinase inhibitors |
US10935544B2 (en) | 2015-09-04 | 2021-03-02 | Obi Pharma, Inc. | Glycan arrays and method of use |
WO2017044434A1 (en) | 2015-09-11 | 2017-03-16 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
EP4360646A2 (en) | 2015-09-25 | 2024-05-01 | F. Hoffmann-La Roche AG | Anti-tigit antibodies and methods of use |
EP3978500A1 (en) | 2015-12-16 | 2022-04-06 | Genentech, Inc. | Process for the preparation of tricyclic pi3k inhibitor compounds |
EP3862365A1 (en) | 2016-01-08 | 2021-08-11 | F. Hoffmann-La Roche AG | Methods of treating cea-positive cancers using pd-1 axis binding antagonists and anti-cea/anti-cd3 bispecific antibodies |
EP4155415A1 (en) | 2016-02-29 | 2023-03-29 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2017151502A1 (en) | 2016-02-29 | 2017-09-08 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
US10980894B2 (en) | 2016-03-29 | 2021-04-20 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
US11041017B2 (en) | 2016-03-29 | 2021-06-22 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
US11833223B2 (en) | 2016-03-29 | 2023-12-05 | Obi Pharma, Inc. | Antibodies, pharmaceutical compositions and methods |
WO2017180581A1 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2017181079A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
WO2017181111A2 (en) | 2016-04-15 | 2017-10-19 | Genentech, Inc. | Methods for monitoring and treating cancer |
US11583577B2 (en) | 2016-04-22 | 2023-02-21 | Obi Pharma, Inc. | Cancer immunotherapy by immune activation or immune modulation via Globo series antigens |
US11261187B2 (en) | 2016-04-22 | 2022-03-01 | Duke University | Compounds and methods for targeting HSP90 |
WO2017194554A1 (en) | 2016-05-10 | 2017-11-16 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Combinations therapies for the treatment of cancer |
WO2017205538A1 (en) | 2016-05-24 | 2017-11-30 | Genentech, Inc. | Pyrazolopyridine derivatives for the treatment of cancer |
EP4067347A1 (en) | 2016-05-24 | 2022-10-05 | Genentech, Inc. | Heterocyclic inhibitors of cbp/ep300 for the treatment of cancer |
WO2017205536A2 (en) | 2016-05-24 | 2017-11-30 | Genentech, Inc. | Therapeutic compounds and uses thereof |
US11365256B2 (en) | 2016-06-08 | 2022-06-21 | Xencor, Inc. | Methods and compositions for inhibiting CD32B expressing cells in IGG4-related diseases |
WO2017214373A1 (en) | 2016-06-08 | 2017-12-14 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2017214452A1 (en) | 2016-06-08 | 2017-12-14 | Xencor, Inc. | Treatment of igg4-related diseases with anti-cd19 antibodies crossbinding to cd32b |
US11642400B2 (en) | 2016-07-27 | 2023-05-09 | Obi Pharma, Inc. | Immunogenic/therapeutic glycan compositions and uses thereof |
US11643456B2 (en) | 2016-07-29 | 2023-05-09 | Obi Pharma, Inc. | Human antibodies, pharmaceutical compositions and methods |
US11046776B2 (en) | 2016-08-05 | 2021-06-29 | Genentech, Inc. | Multivalent and multiepitopic antibodies having agonistic activity and methods of use |
WO2018027204A1 (en) | 2016-08-05 | 2018-02-08 | Genentech, Inc. | Multivalent and multiepitopic anitibodies having agonistic activity and methods of use |
WO2018029124A1 (en) | 2016-08-08 | 2018-02-15 | F. Hoffmann-La Roche Ag | Therapeutic and diagnostic methods for cancer |
WO2018039205A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating breast cancer |
WO2018039203A1 (en) | 2016-08-23 | 2018-03-01 | Oncopep, Inc. | Peptide vaccines and durvalumab for treating multiple myeloma |
WO2018064076A1 (en) | 2016-09-27 | 2018-04-05 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules |
EP4089116A1 (en) | 2016-09-27 | 2022-11-16 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules |
US11655282B2 (en) | 2016-09-27 | 2023-05-23 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules |
US11767298B2 (en) | 2016-09-29 | 2023-09-26 | Duke University | Substituted benzimidazoles as inhibitors of transforming growth factor-β kinase |
US10207998B2 (en) | 2016-09-29 | 2019-02-19 | Duke University | Substituted benzimidazole and substituted benzothiazole inhibitors of transforming growth factor-β kinase and methods of use thereof |
US10927083B2 (en) | 2016-09-29 | 2021-02-23 | Duke University | Substituted benzimidazoles as inhibitors of transforming growth factor-β kinase |
WO2018068028A1 (en) | 2016-10-06 | 2018-04-12 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2018081648A2 (en) | 2016-10-29 | 2018-05-03 | Genentech, Inc. | Anti-mic antibidies and methods of use |
US11000601B2 (en) | 2016-11-21 | 2021-05-11 | Obi Pharma, Inc. | Conjugated biological molecules, pharmaceutical compositions and methods |
US11285135B2 (en) | 2016-12-22 | 2022-03-29 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
EP4001269A1 (en) | 2016-12-22 | 2022-05-25 | Amgen Inc. | Benzoisothiazole, isothiazolo[3,4-b]pyridine, quinazoline, phthalazine, pyrido[2,3-d]pyridazine and pyrido[2,3-d]pyrimidine derivatives as kras g12c inhibitors for treating lung, pancreatic or colorectal cancer |
US10532042B2 (en) | 2016-12-22 | 2020-01-14 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2018119183A2 (en) | 2016-12-22 | 2018-06-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2018160841A1 (en) | 2017-03-01 | 2018-09-07 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2018189220A1 (en) | 2017-04-13 | 2018-10-18 | F. Hoffmann-La Roche Ag | An interleukin-2 immunoconjugate, a cd40 agonist, and optionally a pd-1 axis binding antagonist for use in methods of treating cancer |
US10519146B2 (en) | 2017-05-22 | 2019-12-31 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2018217651A1 (en) | 2017-05-22 | 2018-11-29 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
EP3974429A1 (en) | 2017-05-22 | 2022-03-30 | Amgen Inc. | Precursors of kras g12c inhibitors |
US11905281B2 (en) | 2017-05-22 | 2024-02-20 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2019018757A1 (en) | 2017-07-21 | 2019-01-24 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2019033043A2 (en) | 2017-08-11 | 2019-02-14 | Genentech, Inc. | Anti-cd8 antibodies and uses thereof |
US10640504B2 (en) | 2017-09-08 | 2020-05-05 | Amgen Inc. | Inhibitors of KRAS G12C and methods of using the same |
WO2019051296A1 (en) | 2017-09-08 | 2019-03-14 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2019051291A1 (en) | 2017-09-08 | 2019-03-14 | Amgen Inc. | Inhibitors of kras g12c and methods of using the same |
US11306087B2 (en) | 2017-09-08 | 2022-04-19 | Amgen Inc. | Inhibitors of KRAS G12C and methods of using the same |
EP4141005A1 (en) | 2017-09-08 | 2023-03-01 | Amgen Inc. | Inhibitors of kras g12c and methods of using the same |
US11708423B2 (en) | 2017-09-26 | 2023-07-25 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules and methods of use |
WO2019067328A1 (en) | 2017-09-26 | 2019-04-04 | Cero Therapeutics, Inc. | Chimeric engulfment receptor molecules and methods of use |
WO2019083962A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | Peptide vaccines and pembrolizumab for treating breast cancer |
WO2019083960A1 (en) | 2017-10-24 | 2019-05-02 | Oncopep, Inc. | Peptide vaccines and hdac inhibitors for treating multiple myeloma |
WO2019090263A1 (en) | 2017-11-06 | 2019-05-09 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2019099311A1 (en) | 2017-11-19 | 2019-05-23 | Sunshine Lake Pharma Co., Ltd. | Substituted heteroaryl compounds and methods of use |
US11602534B2 (en) | 2017-12-21 | 2023-03-14 | Hefei Institutes Of Physical Science, Chinese Academy Of Sciences | Pyrimidine derivative kinase inhibitors |
WO2019119486A1 (en) | 2017-12-21 | 2019-06-27 | 中国科学院合肥物质科学研究院 | Class of pyrimidine derivative kinase inhibitors |
WO2019143874A1 (en) | 2018-01-20 | 2019-07-25 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
WO2019148036A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
WO2019148043A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
WO2019148044A1 (en) | 2018-01-26 | 2019-08-01 | Exelixis, Inc. | Compounds for the treatment of kinase-dependent disorders |
WO2019165434A1 (en) | 2018-02-26 | 2019-08-29 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2019191339A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Expression vectors for chimeric engulfment receptors, genetically modified host cells, and uses thereof |
WO2019191334A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
WO2019191340A1 (en) | 2018-03-28 | 2019-10-03 | Cero Therapeutics, Inc. | Cellular immunotherapy compositions and uses thereof |
US11090304B2 (en) | 2018-05-04 | 2021-08-17 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
US11766436B2 (en) | 2018-05-04 | 2023-09-26 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
US11045484B2 (en) | 2018-05-04 | 2021-06-29 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2019213526A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019213516A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
US10988485B2 (en) | 2018-05-10 | 2021-04-27 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2019217691A1 (en) | 2018-05-10 | 2019-11-14 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
WO2019226514A2 (en) | 2018-05-21 | 2019-11-28 | Nanostring Technologies, Inc. | Molecular gene signatures and methods of using same |
WO2019232419A1 (en) | 2018-06-01 | 2019-12-05 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
US11096939B2 (en) | 2018-06-01 | 2021-08-24 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
WO2019241157A1 (en) | 2018-06-11 | 2019-12-19 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
EP4268898A2 (en) | 2018-06-11 | 2023-11-01 | Amgen Inc. | Kras g12c inhibitors for treating cancer |
US11285156B2 (en) | 2018-06-12 | 2022-03-29 | Amgen Inc. | Substituted piperazines as KRAS G12C inhibitors |
WO2020050890A2 (en) | 2018-06-12 | 2020-03-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
WO2019246557A1 (en) | 2018-06-23 | 2019-12-26 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, a platinum agent, and a topoisomerase ii inhibitor |
US11203645B2 (en) | 2018-06-27 | 2021-12-21 | Obi Pharma, Inc. | Glycosynthase variants for glycoprotein engineering and methods of use |
EP3822263A4 (en) * | 2018-07-04 | 2022-03-16 | Daiichi Sankyo Company, Limited | Biaryl ether-type quinazoline derivative |
WO2020018789A1 (en) | 2018-07-18 | 2020-01-23 | Genentech, Inc. | Methods of treating lung cancer with a pd-1 axis binding antagonist, an antimetabolite, and a platinum agent |
WO2020023628A1 (en) | 2018-07-24 | 2020-01-30 | Hygia Pharmaceuticals, Llc | Compounds, derivatives, and analogs for cancer |
WO2020051099A1 (en) | 2018-09-03 | 2020-03-12 | Genentech, Inc. | Carboxamide and sulfonamide derivatives useful as tead modulators |
WO2020061060A1 (en) | 2018-09-19 | 2020-03-26 | Genentech, Inc. | Therapeutic and diagnostic methods for bladder cancer |
EP4249917A2 (en) | 2018-09-21 | 2023-09-27 | F. Hoffmann-La Roche AG | Diagnostic methods for triple-negative breast cancer |
WO2020061349A1 (en) | 2018-09-21 | 2020-03-26 | Genentech, Inc. | Diagnostic methods for triple-negative breast cancer |
US11034672B1 (en) | 2018-09-25 | 2021-06-15 | Black Diamond Therapeutics, Inc. | Tyrosine kinase inhibitor compositions, methods of making and methods of use |
WO2020070239A1 (en) | 2018-10-04 | 2020-04-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Egfr inhibitors for treating keratodermas |
WO2020081767A1 (en) | 2018-10-18 | 2020-04-23 | Genentech, Inc. | Diagnostic and therapeutic methods for sarcomatoid kidney cancer |
WO2020102730A1 (en) | 2018-11-16 | 2020-05-22 | Amgen Inc. | Improved synthesis of key intermediate of kras g12c inhibitor compound |
US11299491B2 (en) | 2018-11-16 | 2022-04-12 | Amgen Inc. | Synthesis of key intermediate of KRAS G12C inhibitor compound |
EP4234546A2 (en) | 2018-11-16 | 2023-08-30 | Amgen Inc. | Improved synthesis of key intermediate of kras g12c inhibitor compound |
US11053226B2 (en) | 2018-11-19 | 2021-07-06 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
US11439645B2 (en) | 2018-11-19 | 2022-09-13 | Amgen Inc. | Combination therapy including a KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers |
WO2020106640A1 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
US11918584B2 (en) | 2018-11-19 | 2024-03-05 | Amgen Inc. | Combination therapy including a KRASG12C inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers |
WO2020106647A2 (en) | 2018-11-19 | 2020-05-28 | Amgen Inc. | Combination therapy including a krasg12c inhibitor and one or more additional pharmaceutically active agents for the treatment of cancers |
WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
WO2020132648A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
US11236069B2 (en) | 2018-12-20 | 2022-02-01 | Amgen Inc. | KIF18A inhibitors |
WO2020132653A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
WO2020132649A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
WO2020163589A1 (en) | 2019-02-08 | 2020-08-13 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2020172712A1 (en) | 2019-02-27 | 2020-09-03 | Epiaxis Therapeutics Pty Ltd | Methods and agents for assessing t-cell function and predicting response to therapy |
WO2020176748A1 (en) | 2019-02-27 | 2020-09-03 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-cd20 or anti-cd38 antibodies |
WO2020180770A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heterocyclyl compounds and uses thereof |
WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
WO2020219906A1 (en) * | 2019-04-25 | 2020-10-29 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of tyrosine kinase |
WO2020223233A1 (en) | 2019-04-30 | 2020-11-05 | Genentech, Inc. | Prognostic and therapeutic methods for colorectal cancer |
WO2020226986A2 (en) | 2019-05-03 | 2020-11-12 | Genentech, Inc. | Methods of treating cancer with an anti-pd-l1 antibody |
US11426404B2 (en) | 2019-05-14 | 2022-08-30 | Amgen Inc. | Dosing of KRAS inhibitor for treatment of cancers |
US11236091B2 (en) | 2019-05-21 | 2022-02-01 | Amgen Inc. | Solid state forms |
US11827635B2 (en) | 2019-05-21 | 2023-11-28 | Amgen Inc. | Solid state forms |
WO2021017892A1 (en) | 2019-07-26 | 2021-02-04 | 上海复宏汉霖生物技术股份有限公司 | Method and composition for anti-cd73 antibodies and variants |
WO2021026101A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
WO2021026100A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Pyridine derivatives as kif18a inhibitors |
WO2021026098A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
WO2021026099A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
WO2021046159A1 (en) | 2019-09-04 | 2021-03-11 | Genentech, Inc. | Cd8 binding agents and uses thereof |
WO2021062245A1 (en) | 2019-09-26 | 2021-04-01 | Exelixis, Inc. | Pyridone compounds and methods of use in the modulation of a protein kinase |
WO2021062085A1 (en) | 2019-09-27 | 2021-04-01 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021067875A1 (en) | 2019-10-03 | 2021-04-08 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
WO2021081212A1 (en) | 2019-10-24 | 2021-04-29 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
WO2021083949A1 (en) | 2019-10-29 | 2021-05-06 | F. Hoffmann-La Roche Ag | Bifunctional compounds for the treatment of cancer |
WO2021091956A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021091982A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021091967A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
WO2021092171A1 (en) | 2019-11-06 | 2021-05-14 | Genentech, Inc. | Diagnostic and therapeutic methods for treatment of hematologic cancers |
WO2021092115A1 (en) | 2019-11-08 | 2021-05-14 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
WO2021097110A1 (en) | 2019-11-13 | 2021-05-20 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2021097256A1 (en) | 2019-11-14 | 2021-05-20 | Cohbar, Inc. | Cxcr4 antagonist peptides |
WO2021097207A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
WO2021097212A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
WO2021108683A1 (en) | 2019-11-27 | 2021-06-03 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
WO2021119505A1 (en) | 2019-12-13 | 2021-06-17 | Genentech, Inc. | Anti-ly6g6d antibodies and methods of use |
WO2021127404A1 (en) | 2019-12-20 | 2021-06-24 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
WO2021142026A1 (en) | 2020-01-07 | 2021-07-15 | Revolution Medicines, Inc. | Shp2 inhibitor dosing and methods of treating cancer |
WO2021154761A1 (en) | 2020-01-27 | 2021-08-05 | Genentech, Inc. | Methods for treatment of cancer with an anti-tigit antagonist antibody |
WO2021177980A1 (en) | 2020-03-06 | 2021-09-10 | Genentech, Inc. | Combination therapy for cancer comprising pd-1 axis binding antagonist and il6 antagonist |
WO2021185844A1 (en) | 2020-03-16 | 2021-09-23 | Pvac Medical Technologies Ltd | Use of substance and pharmaceutical composition thereof, and medical treatments or uses thereof |
WO2021194481A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2021202959A1 (en) | 2020-04-03 | 2021-10-07 | Genentech, Inc. | Therapeutic and diagnostic methods for cancer |
WO2021222167A1 (en) | 2020-04-28 | 2021-11-04 | Genentech, Inc. | Methods and compositions for non-small cell lung cancer immunotherapy |
WO2021233534A1 (en) | 2020-05-20 | 2021-11-25 | Pvac Medical Technologies Ltd | Use of substance and pharmaceutical composition thereof, and medical treatments or uses thereof |
WO2021257503A1 (en) | 2020-06-16 | 2021-12-23 | Genentech, Inc. | Methods and compositions for treating triple-negative breast cancer |
WO2021257736A1 (en) | 2020-06-18 | 2021-12-23 | Revolution Medicines, Inc. | Methods for delaying, preventing, and treating acquired resistance to ras inhibitors |
WO2021257124A1 (en) | 2020-06-18 | 2021-12-23 | Genentech, Inc. | Treatment with anti-tigit antibodies and pd-1 axis binding antagonists |
WO2022002874A1 (en) | 2020-06-30 | 2022-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapy and radical surgery |
WO2022002873A1 (en) | 2020-06-30 | 2022-01-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the risk of recurrence and/or death of patients suffering from a solid cancer after preoperative adjuvant therapies |
WO2022020716A1 (en) | 2020-07-24 | 2022-01-27 | Genentech, Inc. | Heterocyclic inhibitors of tead for treating cancer |
WO2022031749A1 (en) | 2020-08-03 | 2022-02-10 | Genentech, Inc. | Diagnostic and therapeutic methods for lymphoma |
WO2022029220A1 (en) | 2020-08-05 | 2022-02-10 | Ellipses Pharma Ltd | Treatment of cancer using a cyclodextrin-containing polymer-topoisomerase inhibitor conjugate and a parp inhibitor |
WO2022036146A1 (en) | 2020-08-12 | 2022-02-17 | Genentech, Inc. | Diagnostic and therapeutic methods for cancer |
WO2022036285A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Compositions and methods for treating cancer with chimeric tim receptors in combination with inhibitors of poly (adp-ribose) polymerase |
WO2022036287A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Anti-cd72 chimeric receptors and uses thereof |
WO2022036265A1 (en) | 2020-08-14 | 2022-02-17 | Cero Therapeutics, Inc. | Chimeric tim receptors and uses thereof |
WO2022047243A1 (en) | 2020-08-27 | 2022-03-03 | Enosi Life Sciences Corp. | Methods and compositions to treat autoimmune diseases and cancer |
WO2022060583A1 (en) | 2020-09-03 | 2022-03-24 | Revolution Medicines, Inc. | Use of sos1 inhibitors to treat malignancies with shp2 mutations |
WO2022050954A1 (en) | 2020-09-04 | 2022-03-10 | Genentech, Inc. | Dosing for treatment with anti-tigit and anti-pd-l1 antagonist antibodies |
WO2022060836A1 (en) | 2020-09-15 | 2022-03-24 | Revolution Medicines, Inc. | Indole derivatives as ras inhibitors in the treatment of cancer |
WO2022066805A1 (en) | 2020-09-23 | 2022-03-31 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
WO2022076462A1 (en) | 2020-10-05 | 2022-04-14 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2022123316A1 (en) | 2020-12-09 | 2022-06-16 | Takeda Pharmaceutical Company Limited | Compositions of guanylyl cyclase c (gcc) antigen binding agents and methods of use thereof |
WO2022133345A1 (en) | 2020-12-18 | 2022-06-23 | Erasca, Inc. | Tricyclic pyridones and pyrimidones |
WO2022140427A1 (en) | 2020-12-22 | 2022-06-30 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
WO2022171745A1 (en) | 2021-02-12 | 2022-08-18 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives for the treatment of cancer |
WO2022178205A1 (en) | 2021-02-19 | 2022-08-25 | Exelixis, Inc. | Pyridone compounds and methods of use |
WO2022183072A1 (en) | 2021-02-26 | 2022-09-01 | Kelonia Therapeutics, Inc. | Lymphocyte targeted lentiviral vectors |
WO2022235870A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
WO2022235864A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Ras inhibitors |
WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
WO2022251296A1 (en) | 2021-05-25 | 2022-12-01 | Erasca, Inc. | Sulfur-containing heteroaromatic tricyclic kras inhibitors |
WO2022266206A1 (en) | 2021-06-16 | 2022-12-22 | Erasca, Inc. | Kras inhibitor conjugates |
WO2022266427A1 (en) * | 2021-06-17 | 2022-12-22 | Black Diamond Therapeutics, Inc. | 4-(aryl-methyl-amino)-quinazoline derivatives and uses thereof |
WO2023001894A1 (en) | 2021-07-20 | 2023-01-26 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their preparation, and uses |
WO2023010097A1 (en) | 2021-07-28 | 2023-02-02 | Cero Therapeutics, Inc. | Chimeric tim4 receptors and uses thereof |
WO2023018699A1 (en) | 2021-08-10 | 2023-02-16 | Erasca, Inc. | Selective kras inhibitors |
WO2023060253A1 (en) | 2021-10-08 | 2023-04-13 | Revolution Medicines, Inc. | Ras inhibitors |
WO2023097195A1 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic indazole compounds and methods of use in the treatment of cancer |
WO2023097194A2 (en) | 2021-11-24 | 2023-06-01 | Genentech, Inc. | Therapeutic compounds and methods of use |
WO2023114954A1 (en) | 2021-12-17 | 2023-06-22 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023144127A1 (en) | 2022-01-31 | 2023-08-03 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon administration, and uses |
EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
WO2023172940A1 (en) | 2022-03-08 | 2023-09-14 | Revolution Medicines, Inc. | Methods for treating immune refractory lung cancer |
WO2023191816A1 (en) | 2022-04-01 | 2023-10-05 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023219613A1 (en) | 2022-05-11 | 2023-11-16 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2023240058A2 (en) | 2022-06-07 | 2023-12-14 | Genentech, Inc. | Prognostic and therapeutic methods for cancer |
WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
WO2024015897A1 (en) | 2022-07-13 | 2024-01-18 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024020432A1 (en) | 2022-07-19 | 2024-01-25 | Genentech, Inc. | Dosing for treatment with anti-fcrh5/anti-cd3 bispecific antibodies |
WO2024030441A1 (en) | 2022-08-02 | 2024-02-08 | National University Corporation Hokkaido University | Methods of improving cellular therapy with organelle complexes |
WO2024033457A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033389A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033388A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydrothiazepine derivatives |
WO2024033458A1 (en) | 2022-08-11 | 2024-02-15 | F. Hoffmann-La Roche Ag | Bicyclic tetrahydroazepine derivatives |
WO2024081916A1 (en) | 2022-10-14 | 2024-04-18 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
WO2024085242A2 (en) | 2022-10-21 | 2024-04-25 | Kawasaki Institute Of Industrial Promotion | Non-fouling or super stealth vesicle |
WO2024088808A1 (en) | 2022-10-24 | 2024-05-02 | Ags Therapeutics Sas | Extracellular vesicles from microalgae, their biodistribution upon intranasal administration, and uses thereof |
WO2024091991A1 (en) | 2022-10-25 | 2024-05-02 | Genentech, Inc. | Therapeutic and diagnostic methods for multiple myeloma |
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