ES2553553T3 - Anticuerpos humanos que se unen a CXCR4 y usos de los mismos - Google Patents
Anticuerpos humanos que se unen a CXCR4 y usos de los mismos Download PDFInfo
- Publication number
- ES2553553T3 ES2553553T3 ES07867192.2T ES07867192T ES2553553T3 ES 2553553 T3 ES2553553 T3 ES 2553553T3 ES 07867192 T ES07867192 T ES 07867192T ES 2553553 T3 ES2553553 T3 ES 2553553T3
- Authority
- ES
- Spain
- Prior art keywords
- seq
- variable region
- chain variable
- heavy chain
- cdr3
- 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.)
- Active
Links
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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- 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
-
- 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
- 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
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6801—Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
- A61K47/6803—Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
- A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
- A61K47/6849—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
Abstract
Un anticuerpo monoclonal humano, o una porción de unión a antígeno del mismo, que se une específicamente a CXCR4 humano nativo expresado sobre una superficie celular y comprende: una CDR1 de la región variable de la cadena pesada que comprende aminoácidos que tienen la secuencia expuesta en SEC ID Nº: 1; una CDR2 de la región variable de la cadena pesada que comprende aminoácidos que tienen la secuencia expuesta en SEC ID Nº: 5; una CDR3 de la región variable de la cadena pesada que comprende aminoácidos que tienen la secuencia expuesta en SEC ID Nº: 9; una CDR1 de la región variable de la cadena ligera que comprende aminoácidos que tienen la secuencia expuesta en SEC ID Nº: 13; una CDR2 de la región variable de la cadena ligera que comprende aminoácidos que tienen la secuencia expuesta en SEC ID Nº: 17; y una CDR3 de la región variable de la cadena ligera que comprende aminoácidos que tienen la secuencia expuesta en SEC ID Nº: 21.
Description
5
15
25
35
45
55
65
- (a)
- una CDR1 de la región variable de la cadena pesada que comprende una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 1-4;
- (b)
- una CDR2 de la región variable de la cadena pesada que comprende una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 5-8;
- (c)
- una CDR3 de la región variable de la cadena pesada que comprende una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 9-12;
- (d)
- una CDR1 de la región variable de la cadena ligera que comprende una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 13-16;
- (e)
- una CDR2 de la región variable de la cadena ligera que comprende una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 17-20; y
- (f)
- una CDR3 de la región variable de la cadena ligera que comprende una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 21-24; en el que el anticuerpo se une específicamente a CXCR4, preferentemente a CXCR4 humano.
En una realización preferida, el anticuerpo comprende:
- (a)
- una CDR1 de la región variable de la cadena pesada que comprende SEC ID Nº: 1;
- (b)
- una CDR2 de la región variable de la cadena pesada que comprende SEC ID Nº: 5;
- (c)
- una CDR3 de la región variable de la cadena pesada que comprende SEC ID Nº: 9;
- (d)
- una CDR1 de la región variable de la cadena ligera que comprende SEC ID Nº: 13;
- (e)
- una CDR2 de la región variable de la cadena ligera que comprende SEC ID Nº: 17; y
- (f)
- una CDR3 de la región variable de la cadena ligera que comprende SEC ID Nº: 21.
En otra realización preferida, el anticuerpo comprende:
- (a)
- una CDR1 de la región variable de la cadena pesada que comprende SEC ID Nº: 2;
- (b)
- una CDR2 de la región variable de la cadena pesada que comprende SEC ID Nº: 6;
- (c)
- una CDR3 de la región variable de la cadena pesada que comprende SEC ID Nº: 10;
- (d)
- una CDR1 de la región variable de la cadena ligera que comprende SEC ID Nº: 14;
- (e)
- una CDR2 de la región variable de la cadena ligera que comprende SEC ID Nº: 18; y
- (f)
- una CDR3 de la región variable de la cadena ligera que comprende SEC ID Nº: 22.
En otra realización preferida, el anticuerpo comprende:
- (a)
- una CDR1 de la región variable de la cadena pesada que comprende SEC ID Nº: 3;
- (b)
- una CDR2 de la región variable de la cadena pesada que comprende SEC ID Nº: 7;
- (c)
- una CDR3 de la región variable de la cadena pesada que comprende SEC ID Nº: 11;
- (d)
- una CDR2 de la región variable de la cadena ligera que comprende SEC ID Nº: 15;
- (e)
- una CDR2 de la región variable de la cadena ligera que comprende SEC ID Nº: 19; y
- (f)
- una CDR3 de la región variable de la cadena ligera que comprende SEC ID Nº: 23.
En otra realización preferida, el anticuerpo comprende:
- (a)
- una CDR1 de la región variable de la cadena pesada que comprende SEC ID Nº: 4;
- (b)
- una CDR2 de la región variable de la cadena pesada que comprende SEC ID Nº: 8;
- (c)
- una CDR3 de la región variable de la cadena pesada que comprende SEC ID Nº: 12;
- (d)
- una CDR1 de la región variable de la cadena ligera que comprende SEC ID Nº: 16;
(e) una CDR2 de la región variable de la cadena ligera que comprende SEC ID Nº: 20; y
- (f)
- una CDR3 de la región variable de la cadena ligera que comprende SEC ID Nº: 24.
Se conoce bien en la materia que el dominio CDR3, independientemente del (de los) dominio(s) CDR1 y/o CDR2, puede determinar por sí solo la especificidad de unión de un anticuerpo por un antígeno relacionado, y que pueden generarse predeciblemente múltiples anticuerpos que tienen la misma especificidad de unión basándose en una secuencia CDR3 común. Véase, por ejemplo, Klimka et al, British J. of Cancer 83(2):252-260 (2000) (que describe la producción de un anticuerpo anti-CD30 humanizado usando únicamente CDR3 del dominio variable de la cadena pesada del anticuerpo murino anti-CD30 Ki-4); Beiboer et aI., J Mol. Biol. 296:833-849 (2000) (que describe anticuerpos recombinantes de glicoproteína-2 epitelial (EGP-2) usando únicamente la secuencia CDR3 de la cadena pesada del anticuerpo parental murino MOC-31 anti-EGP-2); Rader et al., Proc. Natl. Acad. Sci., U.S.A. 95:89108915 (1998) (que describe un panel de anticuerpos anti-integrina aυβ3 humanizados usando una CDR3 del dominio variable de la cadena pesada y ligera de un anticuerpo murino anti-integrina aυβ3 LM609, en el que cada anticuerpo integrante comprende una secuencia distinta fuera del dominio CDR3 y capaz de unirse al mismo epítope que el anticuerpo murino parental con afinidades tan altas como el anticuerpo parental murino o mayores); Barbas et al., J. Am. Chem. Soc. 116:2161-2162 (1994) (que divulga que el dominio CDR3 proporciona la contribución más significativa a la unión de antígeno); Barbas et al., Proc. Natl. Acad. Sci., U.S.A. 92:2529-2533 (1995) (que describe el injerto de secuencias CDR3 de la cadena pesada de tres Fab (SI-1, SI-40 y SI-32) contra el ADN placentario humano en la cadena pesada de un Fab anti-toxoide tetánico sustituyendo de este modo la CDR3 de la cadena
12
5
15
25
35
45
55
65
interacciones anticuerpo-antígeno, es posible expresar anticuerpos recombinantes que imitan las propiedades de anticuerpos específicos que existen de forma natural construyendo vectores de expresión que incluyen secuencias CDR del anticuerpo específico que existe de forma natural injertado en secuencias de la región estructural de un anticuerpo diferente con propiedades diferentes (véanse, por ejemplo, Riechmann, L. et al. (1998) Nature 332:323327; Jones, P. et al. (1986) Nature 321:522-525; Queen, C. et al (1989) Proc. Natl. Acad Sci. U.S.A. 86:1002910033; patente de EE.UU. Nº 5.225.539 de Winter, y patentes de EE.UU. Nº 5.530.101; 5.585.089; 5.693.762 y
Por consiguiente, otra realización de la presente divulgación se refiere a un anticuerpo monoclonal aislado, o porción de unión a antígeno del mismo, que comprende una región variable de la cadena pesada que comprende secuencias CDR1, CDR2 y CDR3 que comprenden una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 1-4, SEC ID Nº: 5-8 y SEC ID Nº: 9-12, respectivamente, y una región variable de la cadena ligera que comprende secuencias CDR1, CDR2 y CDR3 que comprenden una secuencia de aminoácidos seleccionada del grupo que consiste en SEC ID Nº: 13-16, SEC ID Nº: 17-20 y SEC ID Nº: 21-24, respectivamente. Así, tales anticuerpos contienen las secuencias CDR de VH y VL de anticuerpos monoclonales F7, F9, D1 o E2, pero pueden contener secuencias de la región estructural diferentes de estos anticuerpos.
Tales secuencias de la región estructural pueden obtenerse a partir de bases de datos de ADN públicas o referencias publicadas que incluyen secuencias de genes de anticuerpos de la línea germinal. Por ejemplo, pueden encontrarse secuencias de ADN de la línea germinal para genes de las regiones variables de la cadena pesada y ligera humanas en la base de datos de secuencias de la línea germinal humana “VBase” (disponible de Internet en wmv.mrc-cpe.cam.ac.uk/vbase), además de en Kabat, E, A., et al. (1991) Sequences of Proteins of Immunological Interest, quinta edición, U.S. Department of Health and Human Services, Publicación NIH Nº 91-3242; Tomlinson, I. M., et al (1992) “The Repertoire of Human Germline VH Sequences Reveals about Fifty Groups of VH Segments with Different Hypervariable Loops” J. Mol Biol. 227:776-798; y Cox, J. P. L. et al. (1994) “A Directory of Human Germ-line VH Segments Reveals a Strong Bias in their Usage” Eur. J. Immunol. 24:827-836.
Como otro ejemplo, las secuencias de ADN de la línea germinal para genes de la región variable de la cadena pesada y ligera humanas pueden encontrarse en la base de datos Genbank. Por ejemplo, las siguientes secuencias de la cadena pesada de la línea germinal encontradas en el ratón HCo7 HuMAb están disponibles en los números de acceso a Genbank que se indican a continuación: 1-69 (NG_0010109, NT_024637 y BC070333), 3-33 (NG_0010109 y NT_024637) y 3-7 (NG_0010109 y NT_024637). Como otro ejemplo, las siguientes secuencias de la cadena pesada de la línea germinal encontradas en el ratón HCo12 HuMAb están disponibles en los números de acceso a Genbank que se indican a continuación: 1-69 (NG_0010109, NT_024637 y BC070333), 5-51 (NG_0010109 y NT_024637), 4-34 (NG_0010109 y NT_024637), 3-30.3 (CAJ556644) y 3-23 (AJ406678). Otra fuente adicional de secuencias de la cadena pesada y ligera de la línea germinal humana es la base de datos de genes de inmunoglobulina humana disponibles de IMGT (http://imgt.cines.fr).
Se comparan secuencias de proteínas del anticuerpo con una base de datos de secuencias de proteínas recopiladas usando uno de los métodos de búsqueda de similitud de secuencias llamado Gapped BLAST (Altschul et al. (1997) Nucleic Acids Research 25:3389-3402), que es muy conocido para aquellos expertos en la materia. BLAST es un algoritmo heurístico en el que una alineación estadísticamente significativa entre la secuencia del anticuerpo y la secuencia de la base de datos es probable que contenga pares de segmentos de alto puntuación (HSP) de palabras alineadas. Los pares de segmentos cuyas puntuaciones no pueden mejorarse por extensión o recorte se conocen como un hit (acierto). Resumidamente, las secuencias de nucleótidos de origen VBASE (http://vbase.mrccpe.cam.ac.uk/vbasel/list2.php) se traducen y se retiene la región entre y que incluye las regiones estructurales de FR1 a FR3. Las secuencias de la base de datos tienen una longitud promedio de 98 residuos. Se descartan las secuencias duplicadas que son coincidencias exactas en toda la longitud de la proteína. Una búsqueda BLAST para proteínas usando el programa blastp con parámetros estándar por defecto, excepto el filtro de baja complejidad, que está desconectado, y la matriz de sustitución de BLOSUM62, filtra los 5 aciertos principales que dan coincidencias de secuencia. Las secuencias de nucleótidos se traducen en los seis marcos y el marco sin codones de parada en el segmento coincidente de la secuencia de la base de datos se considera el posible acierto. Esto se confirma a su vez usando el programa tblastx de BLAST, que traduce la secuencia del anticuerpo en los 6 marcos y compara aquellas traducciones con las secuencias de nucleótidos VBASE traducidas dinámicamente en los seis marcos. Pueden consultarse similarmente a VBASE otras bases de datos de secuencias de la línea germinal humana, tales como la disponible de IMGT (http://imgt.cines.fr), como se describió anteriormente.
Las identidades son coincidencias exactas de aminoácidos entre la secuencia del anticuerpo y la base de datos de proteínas en toda la longitud de la secuencia. Los positivos (identidades + coincidencia de sustitución) no son idénticos, sino sustituciones de aminoácidos guiadas por la matriz de sustitución BLOSUM62. Si la secuencia del anticuerpo coincide con dos de las secuencias de la base de datos con la misma identidad, se decidiría que el acierto con más positivos es el acierto de la secuencia coincidente.
Secuencias de la región estructural preferidas para uso en los anticuerpos de la presente divulgación son aquellas que son estructuralmente similares a las secuencias de la región estructural usadas por anticuerpos seleccionados de la presente divulgación, por ejemplo, similares a las secuencias de la región estructural VH 3-48 (SEC ID Nº: 49)
17
Claims (1)
-
imagen1 imagen2
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US82785106P | 2006-10-02 | 2006-10-02 | |
US827851P | 2006-10-02 | ||
PCT/US2007/021152 WO2008060367A2 (en) | 2006-10-02 | 2007-10-01 | Human antibodies that bind cxcr4 and uses thereof |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2553553T3 true ES2553553T3 (es) | 2015-12-10 |
Family
ID=39402166
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES07867192.2T Active ES2553553T3 (es) | 2006-10-02 | 2007-10-01 | Anticuerpos humanos que se unen a CXCR4 y usos de los mismos |
ES12155398.6T Active ES2625798T3 (es) | 2006-10-02 | 2007-10-01 | Anticuerpos humanos que se unen a CXCR4 y usos de los mismos |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES12155398.6T Active ES2625798T3 (es) | 2006-10-02 | 2007-10-01 | Anticuerpos humanos que se unen a CXCR4 y usos de los mismos |
Country Status (30)
Country | Link |
---|---|
US (3) | US8450464B2 (es) |
EP (2) | EP2066351B1 (es) |
JP (4) | JP5417175B2 (es) |
KR (3) | KR101722261B1 (es) |
CN (2) | CN101528259B (es) |
AR (2) | AR063086A1 (es) |
AU (1) | AU2007320024B2 (es) |
BR (1) | BRPI0718197A2 (es) |
CA (1) | CA2665239A1 (es) |
CL (1) | CL2007002835A1 (es) |
CY (2) | CY1117036T1 (es) |
DK (2) | DK2486941T3 (es) |
EA (1) | EA018836B1 (es) |
ES (2) | ES2553553T3 (es) |
HK (1) | HK1131904A1 (es) |
HU (2) | HUE027165T2 (es) |
IL (1) | IL197831A (es) |
LT (1) | LT2486941T (es) |
ME (1) | ME02269B (es) |
MX (1) | MX2009003306A (es) |
NO (1) | NO345287B1 (es) |
NZ (1) | NZ575924A (es) |
PL (2) | PL2066351T3 (es) |
PT (2) | PT2486941T (es) |
RS (2) | RS54424B1 (es) |
SG (2) | SG10201608268RA (es) |
SI (2) | SI2486941T1 (es) |
TW (2) | TWI522366B (es) |
WO (1) | WO2008060367A2 (es) |
ZA (1) | ZA200902256B (es) |
Families Citing this family (62)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
PL2041282T3 (pl) | 2006-07-18 | 2018-07-31 | Noxxon Pharma Ag | Kwasy nukleinowe wiążące sdf-i |
US8450464B2 (en) * | 2006-10-02 | 2013-05-28 | Medarex, Inc. | Human monoclonal antibodies that bind CXCR4 |
FR2915102B1 (fr) * | 2007-04-23 | 2014-05-16 | Pf Medicament | Utilisation d'un anticorps anti-cxcr4 pour le traitement du cancer |
US8772257B2 (en) | 2007-08-06 | 2014-07-08 | Noxxon Pharma Ag | SDF-1 binding nucleic acids and the use thereof |
MX2010012435A (es) * | 2008-05-14 | 2011-05-03 | Lilly Co Eli | Anticuerpos anti-cxcr4. |
US7892546B2 (en) | 2008-05-14 | 2011-02-22 | Eli Lilly And Company | Anti-CXCR4 antibodies |
CN102459575A (zh) | 2009-06-05 | 2012-05-16 | 细胞动力国际有限公司 | 重编程t细胞和造血细胞的方法 |
WO2011042398A1 (en) * | 2009-10-09 | 2011-04-14 | Ablynx Nv | Immunoglobulin single variable domain directed against human cxcr4 and other cell associated proteins and methods to generate them |
LT2499161T (lt) * | 2009-11-11 | 2017-11-27 | Ganymed Pharmaceuticals Gmbh | Specifiniai antikūnai, skirti klaudinui 6 (cldn6) |
WO2011083140A1 (en) * | 2010-01-08 | 2011-07-14 | Ablynx Nv | Immunoglobulin single variable domain directed against human cxcr4 |
GB201002238D0 (en) * | 2010-02-10 | 2010-03-31 | Affitech As | Antibodies |
EP2371863A1 (en) * | 2010-03-30 | 2011-10-05 | Pierre Fabre Médicament | Humanized anti CXCR4 antibodies for the treatment of cancer |
WO2011161266A1 (en) * | 2010-06-25 | 2011-12-29 | Ablynx Nv | Improved immunoglobulin single variable domains and constructs thereof directed against cxcr4 |
US20140120555A1 (en) * | 2011-06-20 | 2014-05-01 | Pierre Fabre Medicament | Anti-cxcr4 antibody with effector functions and its use for the treatment of cancer |
WO2012178137A1 (en) | 2011-06-24 | 2012-12-27 | Gillies Stephen D | Light chain immunoglobulin fusion proteins and methods of use thereof |
EP2726634B1 (en) | 2011-07-01 | 2017-02-22 | Dana-Farber Cancer Institute, Inc. | Discovery of a somatic mutation in myd88 gene in lymphoplasmacytic lymphoma |
CA2842169A1 (en) * | 2011-07-20 | 2013-01-24 | Medimmune Limited | Anti-cxcr4 antibodies and methods of use |
AR087363A1 (es) * | 2011-07-29 | 2014-03-19 | Pf Medicament | Uso del anticuerpo i-3859 para la deteccion y diagnostico de los canceres |
AR087364A1 (es) * | 2011-07-29 | 2014-03-19 | Pf Medicament | Anticuerpo anti-cxcr4 y su uso para la deteccion y dianostico de canceres |
LT2776032T (lt) * | 2011-11-09 | 2018-12-10 | Bristol-Myers Squibb Company | Hematologinių piktybinių navikų gydymas anti-cxcr4 antikūnu |
DK2961771T3 (da) * | 2013-02-26 | 2020-03-02 | Roche Glycart Ag | Bispecifikke, T-celle-aktiverende, antigenbindende molekyler, der er specifikke for CD3 og CEA |
ES2791068T3 (es) | 2013-06-28 | 2020-10-30 | X Body Inc | Descubrimiento de antígenos objetivo, cribados fenotípicos y uso de los mismos para la identificación de epítopos objetivo específicos de células objetivo |
CN106211774B (zh) * | 2013-08-02 | 2020-11-06 | 辉瑞公司 | 抗cxcr4抗体及抗体-药物缀合物 |
WO2015019284A2 (en) * | 2013-08-05 | 2015-02-12 | Cambridge Enterprise Limited | Inhibition of cxcr4 signaling in cancer immunotherapy |
AU2014318614B2 (en) * | 2013-09-12 | 2021-01-07 | Dana-Farber Cancer Institute Inc. | Methods for evaluating and treating Waldenstrom's macroglobulinemia |
CA2924879C (en) * | 2013-09-23 | 2023-01-10 | X-Body, Inc. | Methods and compositions for generation of binding agents against cell surface antigens |
JP6837837B2 (ja) | 2013-11-06 | 2021-03-03 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗cxcr4抗体によるc1013g/cxcr4関連ワルデンシュトレームマクログロブリン血症の治療 |
US10612095B2 (en) | 2013-12-06 | 2020-04-07 | Dana-Farber Cancer Institute, Inc. | Methods to distinguish Waldenström's Macroglobulinemia from IgM monoclonal gammopathy of undetermined significance |
WO2015108967A2 (en) * | 2014-01-15 | 2015-07-23 | Medimmune, Llc | Rsv-specific antibodies and functional parts thereof |
EP3188800A4 (en) * | 2014-09-02 | 2018-05-09 | Cedars-Sinai Medical Center | Compositions and methods for treating fibrosing disorders and cancer |
US9982057B2 (en) | 2014-11-17 | 2018-05-29 | Pelican Therapeutics, Inc. | Human TNFRSF25 antibody |
CN107427574B (zh) * | 2015-01-09 | 2022-02-08 | 阿达尔塔有限公司 | Cxcr4结合分子 |
MX2017009144A (es) | 2015-01-14 | 2017-11-22 | Bristol Myers Squibb Co | Dimeros de benzodiazepina unidos con puentes de heteroarileno, conjugados de estos, y sus metodos de preparacion y uso. |
WO2016172722A1 (en) | 2015-04-23 | 2016-10-27 | Nantomics, Llc | Cancer neoepitopes |
WO2016201425A1 (en) | 2015-06-12 | 2016-12-15 | Bristol-Myers Squibb Company | Treatment of cancer by combined blockade of the pd-1 and cxcr4 signaling pathways |
KR20180089433A (ko) | 2015-12-21 | 2018-08-08 | 브리스톨-마이어스 스큅 컴퍼니 | 부위-특이적 접합을 위한 변이체 항체 |
US10525060B2 (en) | 2016-04-29 | 2020-01-07 | Dana-Farber Cancer Institute, Inc. | HCK as a therapeutic target in MYD88 mutated diseases |
KR20190005924A (ko) | 2016-05-10 | 2019-01-16 | 브리스톨-마이어스 스큅 컴퍼니 | 향상된 안정성을 갖는 튜부리신 유사체의 항체-약물 접합체 |
WO2017214547A1 (en) | 2016-06-09 | 2017-12-14 | Pelican Therapeutics, Inc. | Anti-tnfrsf25 antibodies |
JP7461741B2 (ja) | 2016-06-20 | 2024-04-04 | カイマブ・リミテッド | 抗pd-l1およびil-2サイトカイン |
WO2018035391A1 (en) | 2016-08-19 | 2018-02-22 | Bristol-Myers Squibb Company | Seco-cyclopropapyrroloindole compounds, antibody-drug conjugates thereof, and methods of making and use |
WO2018075842A1 (en) | 2016-10-20 | 2018-04-26 | Bristol-Myers Squibb Company | Condensed benzodiazepine derivatives and conjugates made therefrom |
JP2020508697A (ja) * | 2017-01-31 | 2020-03-26 | エム・エス・エム・プロテイン・テクノロジーズ・インコーポレイテッド | 抗cxcr4抗体 |
US10472361B2 (en) | 2017-08-16 | 2019-11-12 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a benzotriazole moiety, conjugates thereof, and methods and uses therefor |
US10508115B2 (en) | 2017-08-16 | 2019-12-17 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having heteroatom-linked aromatic moieties, conjugates thereof, and methods and uses therefor |
US10494370B2 (en) | 2017-08-16 | 2019-12-03 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a pyridine or pyrazine moiety, conjugates thereof, and methods and uses therefor |
US10487084B2 (en) | 2017-08-16 | 2019-11-26 | Bristol-Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a heterobiaryl moiety, conjugates thereof, and methods and uses therefor |
US10457681B2 (en) | 2017-08-16 | 2019-10-29 | Bristol_Myers Squibb Company | Toll-like receptor 7 (TLR7) agonists having a tricyclic moiety, conjugates thereof, and methods and uses therefor |
CN112513079A (zh) * | 2018-03-13 | 2021-03-16 | 拉巴斯大学医院生物医学研究基金会 | 用于癌症免疫疗法的联合激活和扩增的自然杀伤细胞的抗cxcr4抗体 |
WO2019209811A1 (en) | 2018-04-24 | 2019-10-31 | Bristol-Myers Squibb Company | Macrocyclic toll-like receptor 7 (tlr7) agonists |
AU2019277094A1 (en) | 2018-05-29 | 2021-01-21 | Bristol-Myers Squibb Company | Modified self-immolating moieties for use in prodrugs and conjugates and methods of using and making |
US11554120B2 (en) | 2018-08-03 | 2023-01-17 | Bristol-Myers Squibb Company | 1H-pyrazolo[4,3-d]pyrimidine compounds as toll-like receptor 7 (TLR7) agonists and methods and uses therefor |
JP7389803B2 (ja) | 2018-11-30 | 2023-11-30 | ブリストル-マイヤーズ スクイブ カンパニー | グルタミンを含有する軽鎖c末端に伸長部分を含む抗体およびそのコンジュゲートならびにその方法および用途 |
WO2020123425A2 (en) | 2018-12-12 | 2020-06-18 | Bristol-Myers Squibb Company | Antibodies modified for transglutaminase conjugation, conjugates thereof, and methods and uses |
WO2021055306A1 (en) | 2019-09-16 | 2021-03-25 | Bristol-Myers Squibb Company | Dual capture method for analysis of antibody-drug conjugates |
US20220401481A1 (en) | 2019-11-01 | 2022-12-22 | Magenta Therapeutics, Inc. | Dosing regimens for the mobilization of hematopoietic stem and progenitor cells |
US20230090552A1 (en) | 2020-01-08 | 2023-03-23 | Synthis Therapeutics, Inc. | Alk5 inhibitor conjugates and uses thereof |
AU2021263754A1 (en) | 2020-04-27 | 2022-12-01 | Ensoma, Inc. | Methods and compositions for transducing hematopoietic stem and progenitor cells in vivo |
CN112661845B (zh) * | 2020-12-25 | 2022-06-21 | 暨南大学 | 与cxcr4结合的亲和力成熟结合蛋白及其应用 |
CN112521500B (zh) * | 2020-12-25 | 2022-06-24 | 暨南大学 | 与cxcr4结合的亲和力成熟结合蛋白及应用 |
EP4308694A1 (en) | 2021-03-16 | 2024-01-24 | Magenta Therapeutics, Inc. | Dosing regimens for hematopoietic stem cell mobilization for stem cell transplants in multiple myeloma patients |
CN117003876A (zh) * | 2023-08-31 | 2023-11-07 | 恺佧生物科技(上海)有限公司 | 一种Anti-CXCR4膜蛋白抗体及其制备方法和应用 |
Family Cites Families (152)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
US4475196A (en) | 1981-03-06 | 1984-10-02 | Zor Clair G | Instrument for locating faults in aircraft passenger reading light and attendant call control system |
US4447233A (en) | 1981-04-10 | 1984-05-08 | Parker-Hannifin Corporation | Medication infusion pump |
US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US4447224A (en) | 1982-09-20 | 1984-05-08 | Infusaid Corporation | Variable flow implantable infusion apparatus |
US4487603A (en) | 1982-11-26 | 1984-12-11 | Cordis Corporation | Implantable microinfusion pump system |
US4486194A (en) | 1983-06-08 | 1984-12-04 | James Ferrara | Therapeutic device for administering medicaments through the skin |
DE3572982D1 (en) | 1984-03-06 | 1989-10-19 | Takeda Chemical Industries Ltd | Chemically modified lymphokine and production thereof |
US4596556A (en) | 1985-03-25 | 1986-06-24 | Bioject, Inc. | Hypodermic injection apparatus |
US5374548A (en) | 1986-05-02 | 1994-12-20 | Genentech, Inc. | Methods and compositions for the attachment of proteins to liposomes using a glycophospholipid anchor |
MX9203291A (es) | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
GB8601597D0 (en) | 1986-01-23 | 1986-02-26 | Wilson R H | Nucleotide sequences |
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US4954617A (en) | 1986-07-07 | 1990-09-04 | Trustees Of Dartmouth College | Monoclonal antibodies to FC receptors for immunoglobulin G on human mononuclear phagocytes |
US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
US4881175A (en) | 1986-09-02 | 1989-11-14 | Genex Corporation | Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides |
US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
WO1988007089A1 (en) | 1987-03-18 | 1988-09-22 | Medical Research Council | Altered antibodies |
US5013653A (en) | 1987-03-20 | 1991-05-07 | Creative Biomolecules, Inc. | Product and process for introduction of a hinge region into a fusion protein to facilitate cleavage |
US5258498A (en) | 1987-05-21 | 1993-11-02 | Creative Biomolecules, Inc. | Polypeptide linkers for production of biosynthetic proteins |
JPH02500329A (ja) | 1987-05-21 | 1990-02-08 | クリエイテイブ・バイオマリキユールズ・インコーポレーテツド | ターゲット化多機能蛋白質 |
US5132405A (en) | 1987-05-21 | 1992-07-21 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US5091513A (en) | 1987-05-21 | 1992-02-25 | Creative Biomolecules, Inc. | Biosynthetic antibody binding sites |
US4941880A (en) | 1987-06-19 | 1990-07-17 | Bioject, Inc. | Pre-filled ampule and non-invasive hypodermic injection device assembly |
US4790824A (en) | 1987-06-19 | 1988-12-13 | Bioject, Inc. | Non-invasive hypodermic injection device |
GB8717430D0 (en) | 1987-07-23 | 1987-08-26 | Celltech Ltd | Recombinant dna product |
US5677425A (en) | 1987-09-04 | 1997-10-14 | Celltech Therapeutics Limited | Recombinant antibody |
GB8809129D0 (en) | 1988-04-18 | 1988-05-18 | Celltech Ltd | Recombinant dna methods vectors and host cells |
US5476996A (en) | 1988-06-14 | 1995-12-19 | Lidak Pharmaceuticals | Human immune system in non-human animal |
US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
AU634186B2 (en) * | 1988-11-11 | 1993-02-18 | Medical Research Council | Single domain ligands, receptors comprising said ligands, methods for their production, and use of said ligands and receptors |
EP0401384B1 (en) | 1988-12-22 | 1996-03-13 | Kirin-Amgen, Inc. | Chemically modified granulocyte colony stimulating factor |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5108921A (en) | 1989-04-03 | 1992-04-28 | Purdue Research Foundation | Method for enhanced transmembrane transport of exogenous molecules |
US6291158B1 (en) | 1989-05-16 | 2001-09-18 | Scripps Research Institute | Method for tapping the immunological repertoire |
US5064413A (en) | 1989-11-09 | 1991-11-12 | Bioject, Inc. | Needleless hypodermic injection device |
US5312335A (en) | 1989-11-09 | 1994-05-17 | Bioject Inc. | Needleless hypodermic injection device |
US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
WO1991010741A1 (en) | 1990-01-12 | 1991-07-25 | Cell Genesys, Inc. | Generation of xenogeneic antibodies |
US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
US5427908A (en) | 1990-05-01 | 1995-06-27 | Affymax Technologies N.V. | Recombinant library screening methods |
US5712375A (en) | 1990-06-11 | 1998-01-27 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue selex |
US6261774B1 (en) | 1990-06-11 | 2001-07-17 | Gilead Sciences, Inc. | Truncation selex method |
US5789157A (en) | 1990-06-11 | 1998-08-04 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue selex |
US5864026A (en) | 1990-06-11 | 1999-01-26 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue selex |
US5763566A (en) | 1990-06-11 | 1998-06-09 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue SELEX |
US6172197B1 (en) | 1991-07-10 | 2001-01-09 | Medical Research Council | Methods for producing members of specific binding pairs |
GB9015198D0 (en) | 1990-07-10 | 1990-08-29 | Brien Caroline J O | Binding substance |
ES2108048T3 (es) | 1990-08-29 | 1997-12-16 | Genpharm Int | Produccion y utilizacion de animales inferiores transgenicos capaces de producir anticuerpos heterologos. |
US5789650A (en) | 1990-08-29 | 1998-08-04 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
US6300129B1 (en) | 1990-08-29 | 2001-10-09 | Genpharm International | Transgenic non-human animals for producing heterologous antibodies |
US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5877397A (en) | 1990-08-29 | 1999-03-02 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5874299A (en) | 1990-08-29 | 1999-02-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US6255458B1 (en) | 1990-08-29 | 2001-07-03 | Genpharm International | High affinity human antibodies and human antibodies against digoxin |
US5814318A (en) | 1990-08-29 | 1998-09-29 | Genpharm International Inc. | Transgenic non-human animals for producing heterologous antibodies |
US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
GB9021679D0 (en) * | 1990-10-05 | 1990-11-21 | Gorman Scott David | Antibody preparation |
GB9108652D0 (en) | 1991-04-23 | 1991-06-12 | Antisoma Ltd | Immunoreactive compounds |
AU665221B2 (en) | 1991-12-02 | 1995-12-21 | Cambridge Antibody Technology Limited | Production of anti-self antibodies from antibody segment repertoires and displayed on phage |
ES2227512T3 (es) | 1991-12-02 | 2005-04-01 | Medical Research Council | Produccion de anticuerpos contra auto-antigenos a partir de repertorios de segmentos de anticuerpos fijados en un fago. |
CA2124967C (en) | 1991-12-17 | 2008-04-08 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
US5714350A (en) | 1992-03-09 | 1998-02-03 | Protein Design Labs, Inc. | Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region |
WO1993022332A2 (en) | 1992-04-24 | 1993-11-11 | Board Of Regents, The University Of Texas System | Recombinant production of immunoglobulin-like domains in prokaryotic cells |
US5383851A (en) | 1992-07-24 | 1995-01-24 | Bioject Inc. | Needleless hypodermic injection device |
US6765087B1 (en) | 1992-08-21 | 2004-07-20 | Vrije Universiteit Brussel | Immunoglobulins devoid of light chains |
JP3976333B2 (ja) | 1992-09-16 | 2007-09-19 | ザ スクリップス リサーチ インスティチュート | 呼吸合胞体ウイルスに対するヒト中和性モノクローナル抗体 |
GB9223377D0 (en) | 1992-11-04 | 1992-12-23 | Medarex Inc | Humanized antibodies to fc receptors for immunoglobulin on human mononuclear phagocytes |
JP3919830B2 (ja) | 1992-11-28 | 2007-05-30 | 財団法人化学及血清療法研究所 | 抗ネコヘルペスウイルス−1組換え抗体および該抗体をコードする遺伝子断片 |
CA2161351C (en) | 1993-04-26 | 2010-12-21 | Nils Lonberg | Transgenic non-human animals capable of producing heterologous antibodies |
DK0698097T3 (da) | 1993-04-29 | 2001-10-08 | Unilever Nv | Produktion af antistoffer eller (funktionaliserede) fragmenter deraf afledt af Camelidae-immunoglobuliner med tung kæde |
EP0714409A1 (en) | 1993-06-16 | 1996-06-05 | Celltech Therapeutics Limited | Antibodies |
CA2117953C (en) | 1993-10-14 | 2001-12-11 | Tasuku Honjo | Human stromal derived factor 1 alpha and 1 beta and dnas encoding the same |
AU1866895A (en) | 1994-01-04 | 1995-08-01 | Scripps Research Institute, The | Human monoclonal antibodies to herpes simplex virus and methods therefor |
SE9400088D0 (sv) | 1994-01-14 | 1994-01-14 | Kabi Pharmacia Ab | Bacterial receptor structures |
US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6121022A (en) | 1995-04-14 | 2000-09-19 | Genentech, Inc. | Altered polypeptides with increased half-life |
US6013443A (en) | 1995-05-03 | 2000-01-11 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue SELEX |
AU732961B2 (en) | 1995-05-03 | 2001-05-03 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: tissue selex |
US6090382A (en) | 1996-02-09 | 2000-07-18 | Basf Aktiengesellschaft | Human antibodies that bind human TNFα |
US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
EP1724282B1 (en) | 1997-05-21 | 2013-05-15 | Merck Patent GmbH | Method for the production of non-immunogenic proteins |
US5840598A (en) | 1997-08-14 | 1998-11-24 | Micron Technology, Inc. | LOC semiconductor assembled with room temperature adhesive |
DE19742706B4 (de) | 1997-09-26 | 2013-07-25 | Pieris Proteolab Ag | Lipocalinmuteine |
GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
PT1071700E (pt) | 1998-04-20 | 2010-04-23 | Glycart Biotechnology Ag | Modificação por glicosilação de anticorpos para melhorar a citotoxicidade celular dependente de anticorpos |
GB9814383D0 (en) | 1998-07-02 | 1998-09-02 | Cambridge Antibody Tech | Improvements relating to antibodies |
US6951646B1 (en) | 1998-07-21 | 2005-10-04 | Genmab A/S | Anti hepatitis C virus antibody and uses thereof |
ES2694002T3 (es) | 1999-01-15 | 2018-12-17 | Genentech, Inc. | Polipéptido que comprende una región Fc de IgG1 humana variante |
US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
PT1914244E (pt) | 1999-04-09 | 2013-07-26 | Kyowa Hakko Kirin Co Ltd | Processo para regular a actividade de moléculas funcionais sob o ponto de vista imunológico |
US6387620B1 (en) | 1999-07-28 | 2002-05-14 | Gilead Sciences, Inc. | Transcription-free selex |
NZ517372A (en) | 1999-07-29 | 2004-04-30 | Medarex Inc | Human monoclonal antibodies to HER2/neu |
US7605238B2 (en) | 1999-08-24 | 2009-10-20 | Medarex, Inc. | Human CTLA-4 antibodies and their uses |
EP1212422B1 (en) | 1999-08-24 | 2007-02-21 | Medarex, Inc. | Human ctla-4 antibodies and their uses |
US6794132B2 (en) | 1999-10-02 | 2004-09-21 | Biosite, Inc. | Human antibodies |
US6761902B2 (en) | 1999-12-30 | 2004-07-13 | Dana-Farber Cancer Institute, Inc. | Proteoliposomes containing an integral membrane protein having one or more transmembrane domains |
ATE448301T1 (de) | 2000-09-08 | 2009-11-15 | Univ Zuerich | Sammlung von proteinen mit sich wiederholenden sequenzen (repeat proteins), die repetitive sequenzmodule enthalten |
US7138496B2 (en) * | 2002-02-08 | 2006-11-21 | Genetastix Corporation | Human monoclonal antibodies against human CXCR4 |
US6818216B2 (en) | 2000-11-28 | 2004-11-16 | Medimmune, Inc. | Anti-RSV antibodies |
ATE378403T1 (de) | 2000-11-30 | 2007-11-15 | Medarex Inc | Transchromosomale transgen-nagetiere zur herstellung von humänen antikörpern |
US20040001822A1 (en) | 2000-12-29 | 2004-01-01 | Avigdor Levanon | Y1-isolated molecules comprising epitopes containing sulfated moieties, antibodies to such epitopes, and uses thereof |
US20050089932A1 (en) | 2001-04-26 | 2005-04-28 | Avidia Research Institute | Novel proteins with targeted binding |
WO2002088171A2 (en) | 2001-04-26 | 2002-11-07 | Avidia Research Institute | Combinatorial libraries of monomer domains |
US20030157561A1 (en) | 2001-11-19 | 2003-08-21 | Kolkman Joost A. | Combinatorial libraries of monomer domains |
US20040175756A1 (en) | 2001-04-26 | 2004-09-09 | Avidia Research Institute | Methods for using combinatorial libraries of monomer domains |
US20050053973A1 (en) | 2001-04-26 | 2005-03-10 | Avidia Research Institute | Novel proteins with targeted binding |
US20050048512A1 (en) | 2001-04-26 | 2005-03-03 | Avidia Research Institute | Combinatorial libraries of monomer domains |
CA2508763C (en) | 2001-05-11 | 2012-01-24 | Kirin Beer Kabushiki Kaisha | Human antibody producing mouse and method for producing human antibody using the same |
WO2002092780A2 (en) | 2001-05-17 | 2002-11-21 | Diversa Corporation | Novel antigen binding molecules for therapeutic, diagnostic, prophylactic, enzymatic, industrial, and agricultural applications, and methods for generating and screening thereof |
WO2004003019A2 (en) | 2002-06-28 | 2004-01-08 | Domantis Limited | Immunoglobin single variant antigen-binding domains and dual-specific constructs |
EP1399484B1 (en) | 2001-06-28 | 2010-08-11 | Domantis Limited | Dual-specific ligand and its use |
EP1443961B1 (en) | 2001-10-25 | 2009-05-06 | Genentech, Inc. | Glycoprotein compositions |
US7442512B2 (en) * | 2001-11-30 | 2008-10-28 | Chemocentryx, Inc. | Compositions and methods for detecting and treating diseases and conditions related to chemokine receptors |
WO2003074679A2 (en) | 2002-03-01 | 2003-09-12 | Xencor | Antibody optimization |
JPWO2003085107A1 (ja) | 2002-04-09 | 2005-08-11 | 協和醗酵工業株式会社 | ゲノムが改変された細胞 |
WO2003105898A1 (en) | 2002-06-14 | 2003-12-24 | Centocor, Inc. | Modified "s" antibodies |
EP3287144A1 (en) * | 2002-07-03 | 2018-02-28 | ONO Pharmaceutical Co., Ltd. | Immunopotentiating compositions |
EP2330130B1 (en) * | 2002-10-17 | 2014-08-27 | Genmab A/S | Human monoclonal antibodies against CD20 |
EP2267032A3 (en) | 2002-11-08 | 2011-11-09 | Ablynx N.V. | Method of administering therapeutic polypeptides, and polypeptides therefor |
AU2003299581A1 (en) | 2002-12-02 | 2004-06-23 | Abgenix, Inc. | Antibodies against drugs of abuse |
US20050002939A1 (en) * | 2002-12-23 | 2005-01-06 | Albert Zlotnik | Tumor killing/tumor regression using CXCR4 antagonists |
JP2006523090A (ja) | 2002-12-27 | 2006-10-12 | ドマンティス リミテッド | リガンドに、そしてリガンド受容体に特異的な二重特異性単一ドメイン抗体 |
US9259459B2 (en) | 2003-01-31 | 2016-02-16 | Celldex Therapeutics Inc. | Antibody vaccine conjugates and uses therefor |
EP1627062A1 (en) | 2003-05-14 | 2006-02-22 | Domantis Limited | A process for recovering polypeptides that unfold reversibly from a polypeptide repertoire |
MXPA05012571A (es) | 2003-05-21 | 2006-02-08 | Medarex Inc | Anticuerpos monoclonales humanos contra el antigeno protector de bacillus anthracis. |
PL1639011T3 (pl) | 2003-06-30 | 2009-05-29 | Domantis Ltd | Pegilowane przeciwciała jednodomenowe (dAb) |
HN2004000285A (es) | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
US7674618B2 (en) | 2003-09-04 | 2010-03-09 | Medarex, Inc. | Expression vector |
CA2543360A1 (en) | 2003-10-24 | 2005-05-06 | Joost A. Kolkman | Ldl receptor class a and egf domain monomers and multimers |
EP1697520A2 (en) | 2003-12-22 | 2006-09-06 | Xencor, Inc. | Fc polypeptides with novel fc ligand binding sites |
US20060008844A1 (en) | 2004-06-17 | 2006-01-12 | Avidia Research Institute | c-Met kinase binding proteins |
MX2007005884A (es) | 2004-11-16 | 2008-02-12 | Amgen Mountain View Inc | Andamios de proteina y usos de los mismos. |
NZ583153A (en) * | 2004-12-21 | 2011-06-30 | Centocor Ortho Biotech Inc | Anti-IL-12 antibodies, epitopes, compositions, methods and uses |
AU2005325801A1 (en) | 2005-01-31 | 2006-08-03 | Ablynx N.V. | Method for generating variable domain sequences of heavy chain antibodies |
WO2006089141A2 (en) | 2005-02-18 | 2006-08-24 | Dana-Farber Cancer Institute | Antibodies against cxcr4 and methods of use thereof |
US7875278B2 (en) | 2005-02-18 | 2011-01-25 | Medarex, Inc. | Monoclonal antibodies against prostate specific membrane antigen (PSMA) lacking in fucosyl residues |
WO2006096490A2 (en) | 2005-03-08 | 2006-09-14 | Pharmacia & Upjohn Company Llc | ANTI-MAdCAM ANTIBODY COMPOSITIONS |
EP1929073A4 (en) | 2005-09-27 | 2010-03-10 | Amunix Inc | PROTEIN MEDICAMENT AND ITS USE |
WO2007059782A1 (en) | 2005-11-28 | 2007-05-31 | Genmab A/S | Recombinant monovalent antibodies and methods for production thereof |
US8450464B2 (en) * | 2006-10-02 | 2013-05-28 | Medarex, Inc. | Human monoclonal antibodies that bind CXCR4 |
LT2776032T (lt) * | 2011-11-09 | 2018-12-10 | Bristol-Myers Squibb Company | Hematologinių piktybinių navikų gydymas anti-cxcr4 antikūnu |
JP6837837B2 (ja) * | 2013-11-06 | 2021-03-03 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | 抗cxcr4抗体によるc1013g/cxcr4関連ワルデンシュトレームマクログロブリン血症の治療 |
-
2007
- 2007-10-01 US US12/444,130 patent/US8450464B2/en active Active
- 2007-10-01 KR KR1020097008520A patent/KR101722261B1/ko active IP Right Grant
- 2007-10-01 EP EP07867192.2A patent/EP2066351B1/en active Active
- 2007-10-01 PL PL07867192T patent/PL2066351T3/pl unknown
- 2007-10-01 CA CA002665239A patent/CA2665239A1/en not_active Abandoned
- 2007-10-01 AR ARP070104347A patent/AR063086A1/es active IP Right Grant
- 2007-10-01 ME MEP-2015-771A patent/ME02269B/me unknown
- 2007-10-01 DK DK12155398.6T patent/DK2486941T3/en active
- 2007-10-01 EA EA200900424A patent/EA018836B1/ru not_active IP Right Cessation
- 2007-10-01 JP JP2009531416A patent/JP5417175B2/ja active Active
- 2007-10-01 TW TW096136759A patent/TWI522366B/zh not_active IP Right Cessation
- 2007-10-01 WO PCT/US2007/021152 patent/WO2008060367A2/en active Application Filing
- 2007-10-01 CN CN200780040511.4A patent/CN101528259B/zh active Active
- 2007-10-01 HU HUE07867192A patent/HUE027165T2/en unknown
- 2007-10-01 RS RS20150771A patent/RS54424B1/en unknown
- 2007-10-01 SI SI200731920T patent/SI2486941T1/sl unknown
- 2007-10-01 SG SG10201608268RA patent/SG10201608268RA/en unknown
- 2007-10-01 EP EP12155398.6A patent/EP2486941B1/en active Active
- 2007-10-01 ES ES07867192.2T patent/ES2553553T3/es active Active
- 2007-10-01 DK DK07867192.2T patent/DK2066351T3/en active
- 2007-10-01 HU HUE12155398A patent/HUE033630T2/en unknown
- 2007-10-01 AU AU2007320024A patent/AU2007320024B2/en not_active Ceased
- 2007-10-01 TW TW104133865A patent/TWI592425B/zh not_active IP Right Cessation
- 2007-10-01 PL PL12155398T patent/PL2486941T3/pl unknown
- 2007-10-01 SI SI200731704T patent/SI2066351T1/sl unknown
- 2007-10-01 MX MX2009003306A patent/MX2009003306A/es active IP Right Grant
- 2007-10-01 LT LTEP12155398.6T patent/LT2486941T/lt unknown
- 2007-10-01 PT PT121553986T patent/PT2486941T/pt unknown
- 2007-10-01 PT PT78671922T patent/PT2066351E/pt unknown
- 2007-10-01 ES ES12155398.6T patent/ES2625798T3/es active Active
- 2007-10-01 SG SG2011071958A patent/SG178712A1/en unknown
- 2007-10-01 RS RS20170519A patent/RS55740B1/sr unknown
- 2007-10-01 NZ NZ575924A patent/NZ575924A/en unknown
- 2007-10-01 CN CN201410083654.5A patent/CN103897058B/zh active Active
- 2007-10-01 BR BRPI0718197-3A2A patent/BRPI0718197A2/pt not_active Application Discontinuation
- 2007-10-01 KR KR1020157014573A patent/KR20150065959A/ko not_active Application Discontinuation
- 2007-10-01 KR KR1020177030856A patent/KR20170123712A/ko not_active Application Discontinuation
- 2007-10-02 CL CL200702835A patent/CL2007002835A1/es unknown
-
2009
- 2009-03-26 IL IL197831A patent/IL197831A/en active IP Right Grant
- 2009-03-30 NO NO20091283A patent/NO345287B1/no unknown
- 2009-04-01 ZA ZA2009/02256A patent/ZA200902256B/en unknown
- 2009-12-01 HK HK09111264.7A patent/HK1131904A1/xx unknown
-
2013
- 2013-05-23 US US13/900,791 patent/US10106615B2/en active Active
- 2013-07-24 JP JP2013153626A patent/JP6097650B2/ja active Active
-
2015
- 2015-12-09 CY CY20151101127T patent/CY1117036T1/el unknown
-
2016
- 2016-01-28 JP JP2016014621A patent/JP6496673B2/ja active Active
-
2017
- 2017-06-13 CY CY20171100625T patent/CY1118949T1/el unknown
-
2018
- 2018-04-26 AR ARP180101084A patent/AR113225A2/es unknown
- 2018-10-12 US US16/159,306 patent/US11312777B2/en active Active
- 2018-11-02 JP JP2018207100A patent/JP2019054798A/ja not_active Withdrawn
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2553553T3 (es) | Anticuerpos humanos que se unen a CXCR4 y usos de los mismos | |
US11292834B2 (en) | Therapeutic CD47 antibodies | |
JP7143452B2 (ja) | CD47とSIRPaの相互作用を遮断できる抗体及びその応用 | |
RU2742691C2 (ru) | Cd3-связывающий домен | |
RU2563830C2 (ru) | Лечение остеоартрита и боли | |
TWI781130B (zh) | 抗金黃色葡萄球菌溶血素a毒素之人類抗體 | |
CN109563159A (zh) | 抗c5抗体及其用途 | |
US11591391B2 (en) | Biological binding molecule | |
ES2720291T3 (es) | Anticuerpos monoclonales para su uso en el diagnóstico y la terapia de cánceres y enfermedades autoinmunitarias | |
KR20190117489A (ko) | 항-bcma 중쇄-단독 항체 | |
KR20200018498A (ko) | 항-bcma 중쇄-단독 항체 | |
CN110099697A (zh) | 用于消融造血干细胞的抗体药物缀合物 | |
CN109715209A (zh) | 用于治疗各种疾病和病症的抑制masp-3的组合物和方法 | |
KR20210032311A (ko) | Cd19에 결합하는 중쇄 항체 | |
ES2584916T3 (es) | Composiciones que contienen anticuerpos para tratar enfermedades relacionadas con linfocitos B o T CD5+ HLADR+ | |
KR20200104342A (ko) | Cd22에 결합하는 중쇄 항체 | |
US20220332829A1 (en) | Anti-b7-h3 antibody and application thereof | |
CN109069628A (zh) | 抗pd-1抗体及其用途 | |
JP2022521428A (ja) | 抗炎症剤に連結されたecm親和性ペプチドを用いて炎症性状態および自己免疫状態を処置するための方法および組成物 | |
RU2019121106A (ru) | Иммунотерапия с применением антител, связывающих белок 1 программируемой смерти клеток (pd-1) | |
CN109414426A (zh) | 使用精氨酸耗竭剂的组合癌症免疫疗法 | |
ES2904709T3 (es) | Moléculas de unión que se unen al factor C2B del complemento humano y usos de las mismas | |
Khalid et al. | IgNAR antibody: Structural features, diversity and applications | |
US20220227864A1 (en) | Biological binding molecules | |
TW202019962A (zh) | 標靶CD38及TGF-β的組合療法 |