EP1200098A2 - Combined preparations comprising daunorubicin derivatives and anti her2 antibodies - Google Patents

Combined preparations comprising daunorubicin derivatives and anti her2 antibodies

Info

Publication number
EP1200098A2
EP1200098A2 EP00945903A EP00945903A EP1200098A2 EP 1200098 A2 EP1200098 A2 EP 1200098A2 EP 00945903 A EP00945903 A EP 00945903A EP 00945903 A EP00945903 A EP 00945903A EP 1200098 A2 EP1200098 A2 EP 1200098A2
Authority
EP
European Patent Office
Prior art keywords
recombmant
humanized
antι
her2
antibody
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP00945903A
Other languages
German (de)
French (fr)
Inventor
Cristina Geroni
Marina Ripamonti
Michele Caruso
Antonino Suarato
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pfizer Italia SRL
Original Assignee
Pharmacia Italia SpA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pharmacia Italia SpA filed Critical Pharmacia Italia SpA
Publication of EP1200098A2 publication Critical patent/EP1200098A2/en
Withdrawn legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/32—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products of oncogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies

Definitions

  • the present invention pertains to the field of neoplastic disease therapy.
  • this invention provides an antitumor composition comprising an alkylating anthracycline and a recombmant humanized ant ⁇ -HER2 antibody, for example the recombmant humanized monoclonal antibody (rhuMab) anti-
  • trastuzumab (HerceptmTM) , having a synergistic or additive antmeoplastic effect.
  • the present invention provides, in a first aspect, a pharmaceutical composition for use antmeoplastic therapy m mammals, including humans, comprising
  • a recombmant humanized ant ⁇ -HER2 antibody and a pharmaceutically acceptable carrier or excipient .
  • the recombmant humanized ant ⁇ -HER2 antibody is preferably, the recombmant humanized monoclonal antibody ant ⁇ -HER2 trastuzumab .
  • alkylating anthracyclmes of formula la and lb are 4-demethoxy-3' -deam ⁇ no-3' -az ⁇ r ⁇ dmyl- ' - methansulfonyl daunorubicin (la) and 4-demethoxy-N, N-bis (2- chloroethyl ) -4 ' -methansulfonyl daunorubicin (lb).
  • These alkylating anthracyclmes were described in Anticancer Drug Design (1995), vol. 10, 641-653, and claimed respectively in US-A-5, 532, 218 and US-A-5, 496, 800.
  • the recombmant humanized monoclonal antibody ant ⁇ -HER2 trastuzumab (HerceptinTM) is described in various scientific publications, for example Cancer Res., 1998, 58:2825-2831.
  • the present invention also provides a product comprising an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized ant ⁇ -HER2 antibody, preferably the recombmant humanized monoclonal antibody ant ⁇ -HER2 trastuzumab, as combined preparation for simultaneous, separate or seguential use m antitumor therapy.
  • a further aspect of the present invention is to provide a method of treating a mammal, including a human, suffering from a neoplastic disease comprising administering to said mammal an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized ant ⁇ -HER2 antibody, preferably the recombmant humanized monoclonal antibody anti- HER2 trastuzumab, in amounts effective to produce a synergistic antmeoplastic effect.
  • a still further aspect of the present invention is to provide a method for lowering the side effects caused by antmeoplastic therapy with an antmeoplastic agent a mammal, including a human, in need thereof, the method comprising administering to said mammal a combined preparation comprising an alkylating anthracycline of formula la or lb as defined above, and a recombmant humanized ant ⁇ -HER2 antibody, preferably the the recombmant humanized monoclonal antibody ant ⁇ -HER2 trastuzumab, in amounts effective to produce a synerqistic antmeoplastic effect.
  • a synergistic antmeoplastic effect as used herein is meant the inhibition of the growth tumor, preferably the complete regression of the tumor, administering an effective amount of the combination of an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized ant ⁇ -HER2 antibody to mammals, including humans.
  • parenteral is meant intravenous, subcutaneous and intramuscular administration.
  • Oral administration includes administering the costituents of the combined preparation m a suitable oral form such as, e.g., tablets, capsules, suspensions, solutions, emulsions, powders, syrups and the like.
  • Parenteral administration includes administering the costituents of the combined preparation by subcutaneous, intravenous or intramuscular injections.
  • the actual preferred method and order of administration of the combined preparations of the invention may vary according to, inter alia, the particular pharmaceutical formulation of the alkylating anthracycline of formula la or lb as defined above being utilized, the particular pharmaceutical formulation of the recombmant humanized ant ⁇ -HER2 antibody being utilized, the particular cancer being treated, and the particular patient being treated.
  • the dosage ranges for the administration of the combined preparation may vary with the age, condition, sex and extent of the disease in the patient and can be determined by one of skill m the art.
  • the dosage regimen must therefore be tailored to the particular of the patient's conditions, response and associate treatments m a manner which is conventional for any therapv, and may need to be adjusted in response to changes in conditions and/or in light of other clinical conditions.
  • the alkylating anthracycline may be administered simultaneously with the recombmant humanized ant ⁇ -HER2 antibody, or the compounds may be administered sequentially, in either order.
  • the course of therapy generally employed is from about
  • the course therapy employed is from about 1 to about 50 mg/m 2 of body surface area.
  • the course of therapy generally employed is from about 1 to about 1000 mg/m 2 of body surface area. More preferably, the course therapy employed is from about 50 to about 500 mg/m 2 of body surface area.
  • the antmeoplastic therapy of the present invention is, in particular, suitable for treating breast, ovary, lung, colon, kidney, stomach, pancreas, liver, melanoma, leukemia and brain tumors m mammals, including humans.
  • an alkylating anthracycline according to the invention and a recombmant humanized ant ⁇ -HER2 antibody for example the recombmant humanized monoclonal antibody anti- HER2 trastuzumab, can be suitable for the treatment of patients with cancers over-expressing the HER2 protein, for example, for patient with metastatic breast cancer over- expressing the HER2 protein.
  • the antmeoplastic therapy according to this invention also comprises the prevention and/or treatment of tumor metastasis.
  • a still further aspect of the present invention is the use of an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized ant ⁇ -HER2 antibody, preferably the recombmant humanized monoclonal antibody anti- HER2 trastuzumab, for the treatment of tumors by angiogenesis inhibition .
  • the effectiveness of an alkylating anthracycline of formula la or lb and a recombmant humanized ant ⁇ -HER2 antibody is significantly increased without a parallel increased toxicity.
  • the combined therapy of the present invention enhances the antitumoral effects of the alkylating anthracycline of formula la or lb as defined above and of a recombmant humanized ant ⁇ -HER2 antibody and thus yields the most effective and least toxic treatment for tumors.
  • the synergistic action displayed by the combined preparations according to the present invention can be shown, for instance, by testing the activity of the combination m mice bearing human tumor xenografts overexpressmg HER2 protein, following, for example, the method described in Cancer Research, 1998, 58:2825-2831.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Genetics & Genomics (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

There are provided the combined use of 4-demethoxy-3'-deamino-3'-aziridinyl-4'-methansulfonyl daunorubicin or 4-demethoxy-N,N-bis(2-chloroethyl)-4'-methansulfonyl daunorubicin and a recombinant humanized anti-HER2 antibody, preferably trastuzumab, in the treatment of tumors and the use of said combination in the treatment and/or prevention of tumor metastasis.

Description

Title: "Combined preparations comprising antitumor agents'
The present invention pertains to the field of neoplastic disease therapy. Particularly, this invention provides an antitumor composition comprising an alkylating anthracycline and a recombmant humanized antι-HER2 antibody, for example the recombmant humanized monoclonal antibody (rhuMab) anti-
HER2, trastuzumab (Herceptm™) , having a synergistic or additive antmeoplastic effect.
The present invention provides, in a first aspect, a pharmaceutical composition for use antmeoplastic therapy m mammals, including humans, comprising
- an alkylating anthracycline of formula la or lb
a recombmant humanized antι-HER2 antibody and a pharmaceutically acceptable carrier or excipient . The recombmant humanized antι-HER2 antibody is preferably, the recombmant humanized monoclonal antibody antι-HER2 trastuzumab .
The chemical names of the alkylating anthracyclmes of formula la and lb are 4-demethoxy-3' -deamιno-3' -azιrιdmyl- ' - methansulfonyl daunorubicin (la) and 4-demethoxy-N, N-bis (2- chloroethyl ) -4 ' -methansulfonyl daunorubicin (lb). These alkylating anthracyclmes were described in Anticancer Drug Design (1995), vol. 10, 641-653, and claimed respectively in US-A-5, 532, 218 and US-A-5, 496, 800. Both compounds intercalate into DNA via the chromophore and alkylate guanine at N7 position n DNA minor groove via their reactive moiety on position 3' of the ammo sugar. Compounds la and lb are able to circumvent the resistance to all major classes of cytotoxics, indicating that the compounds represent a new class of cytotoxic antitumor drugs.
The recombmant humanized monoclonal antibody antι-HER2 trastuzumab (Herceptin™) is described in various scientific publications, for example Cancer Res., 1998, 58:2825-2831. The present invention also provides a product comprising an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized antι-HER2 antibody, preferably the recombmant humanized monoclonal antibody antι-HER2 trastuzumab, as combined preparation for simultaneous, separate or seguential use m antitumor therapy.
A further aspect of the present invention is to provide a method of treating a mammal, including a human, suffering from a neoplastic disease comprising administering to said mammal an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized antι-HER2 antibody, preferably the recombmant humanized monoclonal antibody anti- HER2 trastuzumab, in amounts effective to produce a synergistic antmeoplastic effect. A still further aspect of the present invention is to provide a method for lowering the side effects caused by antmeoplastic therapy with an antmeoplastic agent a mammal, including a human, in need thereof, the method comprising administering to said mammal a combined preparation comprising an alkylating anthracycline of formula la or lb as defined above, and a recombmant humanized antι-HER2 antibody, preferably the the recombmant humanized monoclonal antibody antι-HER2 trastuzumab, in amounts effective to produce a synerqistic antmeoplastic effect. By the term "a synergistic antmeoplastic effect" as used herein is meant the inhibition of the growth tumor, preferably the complete regression of the tumor, administering an effective amount of the combination of an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized antι-HER2 antibody to mammals, including humans.
By the term "administered" or "administering" as used herein is meant any acceptable manner of administering a drug to a patient which is medically acceptable including parenteral and oral administration. By "parenteral" is meant intravenous, subcutaneous and intramuscular administration. Oral administration includes administering the costituents of the combined preparation m a suitable oral form such as, e.g., tablets, capsules, suspensions, solutions, emulsions, powders, syrups and the like. Parenteral administration includes administering the costituents of the combined preparation by subcutaneous, intravenous or intramuscular injections. The actual preferred method and order of administration of the combined preparations of the invention may vary according to, inter alia, the particular pharmaceutical formulation of the alkylating anthracycline of formula la or lb as defined above being utilized, the particular pharmaceutical formulation of the recombmant humanized antι-HER2 antibody being utilized, the particular cancer being treated, and the particular patient being treated. The dosage ranges for the administration of the combined preparation may vary with the age, condition, sex and extent of the disease in the patient and can be determined by one of skill m the art. The dosage regimen must therefore be tailored to the particular of the patient's conditions, response and associate treatments m a manner which is conventional for any therapv, and may need to be adjusted in response to changes in conditions and/or in light of other clinical conditions. In the method of the subject invention, the alkylating anthracycline may be administered simultaneously with the recombmant humanized antι-HER2 antibody, or the compounds may be administered sequentially, in either order.
In the method of the subject invention, for the administration of the alkylating anthracycline of formula la or lb as defined above, the course of therapy generally employed is from about
0.1 to about 200 mg/m of body surface area. More preferably, the course therapy employed is from about 1 to about 50 mg/m2 of body surface area.
In the method of the subject invention, for the administration of the recombmant humanized antι-HER2 antibody, for example for the administration of the recombmant humanized monoclonal antibody antι-HER2 trastuzumab, the course of therapy generally employed is from about 1 to about 1000 mg/m2 of body surface area. More preferably, the course therapy employed is from about 50 to about 500 mg/m2 of body surface area.
The antmeoplastic therapy of the present invention is, in particular, suitable for treating breast, ovary, lung, colon, kidney, stomach, pancreas, liver, melanoma, leukemia and brain tumors m mammals, including humans. More in particular, the combined use of an alkylating anthracycline according to the invention and a recombmant humanized antι-HER2 antibody, for example the recombmant humanized monoclonal antibody anti- HER2 trastuzumab, can be suitable for the treatment of patients with cancers over-expressing the HER2 protein, for example, for patient with metastatic breast cancer over- expressing the HER2 protein.
The antmeoplastic therapy according to this invention also comprises the prevention and/or treatment of tumor metastasis. A still further aspect of the present invention is the use of an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized antι-HER2 antibody, preferably the recombmant humanized monoclonal antibody anti- HER2 trastuzumab, for the treatment of tumors by angiogenesis inhibition . As stated above, the effectiveness of an alkylating anthracycline of formula la or lb and a recombmant humanized antι-HER2 antibody is significantly increased without a parallel increased toxicity. In other words, the combined therapy of the present invention enhances the antitumoral effects of the alkylating anthracycline of formula la or lb as defined above and of a recombmant humanized antι-HER2 antibody and thus yields the most effective and least toxic treatment for tumors. The synergistic action displayed by the combined preparations according to the present invention can be shown, for instance, by testing the activity of the combination m mice bearing human tumor xenografts overexpressmg HER2 protein, following, for example, the method described in Cancer Research, 1998, 58:2825-2831.
Suitable modifications and adaptations of a variety of conditions and parameters normally encountered in clinical therapy which are obvious to those skilled m the art are within the scope of this invention.

Claims

1. Products containing an alkylating anthracycline of formula la or lb:
and a recombmant humanized antι-HER2 antibody as a combined preparation for simultaneous, separate or sequential use in antitumor therapy.
2. Products according to claim 1, wherein the recombmant humanized antι-HER2 antibody is the recombmant humanized monoclonal antibody antι-HER2 trastuzumab.
3. Products according to claim 1 or 2, wherein the alkylating anthracycline is 4-demethoxy-3' -deammo-3' -azιrιdιnyl-4 ' - methansulfon 1 daunorubicin.
4. Products according to any one of claims 1 to 3, wherein the antitumor therapy is for treating cancers over-expressing HER2 protein.
5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier or excipient and, as active ingredient, an alkylating anthracycline of formula la or lb as defined m claim 1 and a recombmant humanized antι-HER2 antibody.
6. A pharmaceutical composition according to claim 5 wherein the recombmant humanized antι-HER2 antibody is the recombmant humanized monoclonal antibody antι-HER2 trastuzumab .
7. Use of an alkylating anthracycline of formula la or lb as defined in claim 1 and a recombmant humanized antι-HER2 antibody in the preparation of a medicament for use in the treatment of tumors, wherein the alkylating anthracycline and the recombmant humanized antι-HER2 antibody are administered simultaneously, separately or sequentially.
8. Use according to claim 7 wherein the recombmant humanized antι-HER2 antibody is the recombmant humanized monoclonal antibody antι-HER2 trastuzumab.
9. Use of an alkylating anthracycline of formula la or lb as defined m claim 1 and a recombmant humanized antι-HER2 antibody m the preparation of a medicament for use in the prevention and/or treatment of tumor metastasis, wherein the alkylating anthracycline and the recombmant humanized anti- HER2 antibody are administered simultaneously, separately or sequentially.
10. Use according to claim 9 wherein the recombmant humanized antι-HER2 antibody is the recombmant humanized monoclonal antibody antι-HER2 trastuzumab.
11. A method of treating a mammal, including a human, suffering from a neoplastic disease comprising administering to said mammal an alkylating anthracycline of formula la or lb as defined above and a recombmant humanized antι-HER2 antibody, in amounts effective to produce a synergistic antmeoplastic effect.
12. A method according to claim 11, wherein the recombinant humanized antι-HER2 antibody is the recombinant humanized monoclonal antibody anti-HER2 trastuzumab.
13. A method for lowering the side effects caused by antmeoplastic therapy with an antineoplastic agent in a mammal, including a human, in need thereof, the method comprising administering to said mammal a combined preparation comprising an alkylating anthracycline of formula la or lb as defined above, and a recombinant humanized anti-HER2 antibody, in amounts effective to produce a synergistic antineoplastic effect .
14. A method according to claim 13, wherein the recombinant humanized anti-HER2 antibody is the recombinant humanized monoclonal antibody anti-HER2 trastuzumab.
EP00945903A 1999-07-20 2000-07-10 Combined preparations comprising daunorubicin derivatives and anti her2 antibodies Withdrawn EP1200098A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9917012.8A GB9917012D0 (en) 1999-07-20 1999-07-20 Combined preparations comprising antitumor agents
GB9917012 1999-07-20
PCT/EP2000/006540 WO2001005425A2 (en) 1999-07-20 2000-07-10 Combined preparations comprising daunorubicin derivatives and her2 antibodies

Publications (1)

Publication Number Publication Date
EP1200098A2 true EP1200098A2 (en) 2002-05-02

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Country Status (5)

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EP (1) EP1200098A2 (en)
JP (1) JP2003504413A (en)
AU (1) AU5983900A (en)
GB (1) GB9917012D0 (en)
WO (1) WO2001005425A2 (en)

Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102698265A (en) 2000-05-19 2012-10-03 杰南技术公司 Gene detection assay for improving the likelihood of an effective response to an erbb antagonist cancer therapy
GB0114654D0 (en) * 2001-06-15 2001-08-08 Pharmacia & Upjohn Spa Anti-tumor compound
KR20170134771A (en) 2005-01-21 2017-12-06 제넨테크, 인크. Fixed dosing of her antibodies
KR101253576B1 (en) 2005-02-23 2013-04-11 제넨테크, 인크. Extending time to disease progression or survival in cancer patients using a her dimerization inhibitor
EP2899541A1 (en) 2007-03-02 2015-07-29 Genentech, Inc. Predicting response to a HER dimerisation inhbitor based on low HER3 expression
PL2171090T3 (en) 2007-06-08 2013-09-30 Genentech Inc Gene expression markers of tumor resistance to her2 inhibitor treatment
US9551033B2 (en) 2007-06-08 2017-01-24 Genentech, Inc. Gene expression markers of tumor resistance to HER2 inhibitor treatment
BRPI0812682A2 (en) 2008-06-16 2010-06-22 Genentech Inc metastatic breast cancer treatment
AR075896A1 (en) 2009-03-20 2011-05-04 Genentech Inc ANTI-HER ANTIBODIES (EPIDERMAL GROWTH FACTOR)
SG10201507044PA (en) 2009-05-29 2015-10-29 Hoffmann La Roche Modulators for her2 signaling in her2 expressing patients with gastric cancer
JP5981853B2 (en) 2010-02-18 2016-08-31 ジェネンテック， インコーポレイテッド Neuregulin antagonists and their use in the treatment of cancer
WO2011146568A1 (en) 2010-05-19 2011-11-24 Genentech, Inc. Predicting response to a her inhibitor
EP2643353A1 (en) 2010-11-24 2013-10-02 Novartis AG Multispecific molecules
EP2655413B1 (en) 2010-12-23 2019-01-16 F.Hoffmann-La Roche Ag Polypeptide-polynucleotide-complex and its use in targeted effector moiety delivery
KR20140057326A (en) 2011-08-17 2014-05-12 제넨테크, 인크. Neuregulin antibodies and uses thereof
US9327023B2 (en) 2011-10-25 2016-05-03 The Regents Of The University Of Michigan HER2 targeting agent treatment in non-HER2-amplified cancers having HER2 expressing cancer stem cells
CN106987620A (en) 2011-11-30 2017-07-28 霍夫曼-拉罗奇有限公司 Erbb3 mutation in cancer
EP2788500A1 (en) 2011-12-09 2014-10-15 F.Hoffmann-La Roche Ag Identification of non-responders to her2 inhibitors
WO2013148315A1 (en) 2012-03-27 2013-10-03 Genentech, Inc. Diagnosis and treatments relating to her3 inhibitors
KR102291355B1 (en) 2012-11-30 2021-08-19 에프. 호프만-라 로슈 아게 Identification of patients in need of pd-l1 inhibitor cotherapy
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
US10167342B2 (en) 2016-08-29 2019-01-01 Fazel Shokri Production of hersintuzumab: a new humanized antibody against HER2 for cancer treatment
PT110526B (en) 2018-01-26 2021-02-04 Univ Nova De Lisboa ANTIBODY, FUNCTIONAL FRAGMENT OR PROBE OF THE SAME AGAINST TUMORAL ANTIGENS
IL300314A (en) 2020-10-08 2023-04-01 Affimed Gmbh Trispecific binders
CA3216098A1 (en) 2021-07-30 2023-02-02 Uwe Reusch Duplexbodies
TW202334221A (en) 2021-11-03 2023-09-01 德商安富美德有限公司 Bispecific cd16a binders

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3040121B2 (en) * 1988-01-12 2000-05-08 ジェネンテク，インコーポレイテッド Methods of treating tumor cells by inhibiting growth factor receptor function
IL89220A (en) * 1988-02-11 1994-02-27 Bristol Myers Squibb Co Anthracycline immunoconjugates, their production and pharmaceutical compositions containing them
US5705157A (en) * 1989-07-27 1998-01-06 The Trustees Of The University Of Pennsylvania Methods of treating cancerous cells with anti-receptor antibodies
ZA9811162B (en) * 1997-12-12 2000-06-07 Genentech Inc Treatment with anti-ERBB2 antibodies.
CA2357525A1 (en) * 1999-01-27 2000-08-03 Cornell Research Foundation, Inc. Treating cancers associated with overexpression of her-2/neu
US6333348B1 (en) * 1999-04-09 2001-12-25 Aventis Pharma S.A. Use of docetaxel for treating cancers
EP1187632B1 (en) * 1999-05-14 2008-12-03 Genentech, Inc. TREATMENT WITH ANTI-ErbB2 ANTIBODIES

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0105425A2 *

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AU5983900A (en) 2001-02-05
WO2001005425A2 (en) 2001-01-25
WO2001005425A3 (en) 2001-05-17
JP2003504413A (en) 2003-02-04
GB9917012D0 (en) 1999-09-22

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