ES2580002T3 - Formulación de anticuerpo contra CD40 y procedimientos - Google Patents
Formulación de anticuerpo contra CD40 y procedimientos Download PDFInfo
- Publication number
- ES2580002T3 ES2580002T3 ES10162787.5T ES10162787T ES2580002T3 ES 2580002 T3 ES2580002 T3 ES 2580002T3 ES 10162787 T ES10162787 T ES 10162787T ES 2580002 T3 ES2580002 T3 ES 2580002T3
- Authority
- ES
- Spain
- Prior art keywords
- antibody
- seq
- pta
- human
- procedures
- 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.)
- Expired - Lifetime
Links
- 238000009472 formulation Methods 0.000 title abstract 2
- 239000000203 mixture Substances 0.000 title abstract 2
- 101150013553 CD40 gene Proteins 0.000 title description 4
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 title description 3
- 238000000034 method Methods 0.000 title description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 abstract description 4
- 229940123189 CD40 agonist Drugs 0.000 abstract description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 abstract description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 abstract description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 abstract description 2
- 229920000053 polysorbate 80 Polymers 0.000 abstract description 2
- 229940068968 polysorbate 80 Drugs 0.000 abstract description 2
- 239000001632 sodium acetate Substances 0.000 abstract description 2
- 235000017281 sodium acetate Nutrition 0.000 abstract description 2
- 239000011780 sodium chloride Substances 0.000 abstract description 2
- 239000003937 drug carrier Substances 0.000 abstract 2
- 239000007788 liquid Substances 0.000 abstract 1
- 238000007911 parenteral administration Methods 0.000 abstract 1
- 239000008194 pharmaceutical composition Substances 0.000 abstract 1
- 235000002639 sodium chloride Nutrition 0.000 abstract 1
- 108010087819 Fc receptors Proteins 0.000 description 12
- 102000009109 Fc receptors Human genes 0.000 description 12
- 210000000265 leukocyte Anatomy 0.000 description 11
- 230000009870 specific binding Effects 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 241000282553 Macaca Species 0.000 description 7
- 210000001165 lymph node Anatomy 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 230000027455 binding Effects 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 125000003275 alpha amino acid group Chemical group 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 3
- 229960004316 cisplatin Drugs 0.000 description 3
- 150000003057 platinum Chemical class 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007524 negative regulation of DNA replication Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 230000004543 DNA replication Effects 0.000 description 1
- 102100026122 High affinity immunoglobulin gamma Fc receptor I Human genes 0.000 description 1
- 101000913074 Homo sapiens High affinity immunoglobulin gamma Fc receptor I Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 108010073807 IgG Receptors Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 1
- 238000000684 flow cytometry Methods 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 108010088880 plasmagel Proteins 0.000 description 1
- -1 platinum derivative compound Chemical class 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- 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
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- 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
- A61P37/04—Immunostimulants
-
- 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
- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
-
- 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
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- 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
- C07K2317/74—Inducing cell proliferation
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Endocrinology (AREA)
- Biophysics (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Una formulación farmacéutica líquida adecuada para administración parenteral, que comprende un anticuerpo agonista de CD40 y un vehículo farmacéuticamente aceptable, en la que la formulación está a pH 5,5, en la que el anticuerpo consiste en el anticuerpo 21.4.1, y en la que el vehículo farmacéuticamente aceptable comprende acetato de sodio, cloruro de sodio y polisorbato 80.
Description
(SEQ ID NO: 4) de los anticuerpos 3.1.1 y 3.1.1H-A78T-V88A-V97A/3.1.1LL4M-L83V son iguales. El anticuerpo 3.1.1H-A78T-V88A-V97A/3.1.1L-L4M-L83V también se denomina "3.1.1H3L2" para reflejar que el anticuerpo comprende tres sustituciones de aminoácidos en la cadena pesada y dos sustituciones de aminoácidos en la cadena ligera con respecto al anticuerpo 3.1.1.
5 Por lo tanto, los anticuerpos divulgados se pueden modificar por sustitución, adición o deleción de uno a diez, uno a cinco, o uno a tres residuos de aminoácidos, por ejemplo, en una CDR o región estructural. Los anticuerpos ejemplares y procedimientos de producción de los mismos se describen en detalle en la solicitud provisional de EE. UU. n.º 60/348.980, presentada el 9 de noviembre de 2001, y la solicitud internacional PCT n.º PCT/US02/36107 (WO 03/040170), presentada el 8 de noviembre de 2002. Los hibridomas 3.1.1, 7.1.2, 10.8.3, 15.1.1 y 21.4.1 se
10 depositaron de acuerdo con el Tratado de Budapest, en la American Type Culture Collection (ATCC), 10801 University Boulevard, Manassas, VA 20.110-2209, el 6 de agosto de 2001. Los hibridomas 21.2.1, 22.1.1, 23.5.1, 23.25.1, 23.28.1, 23.29.1 y 24.2.1 se depositaron en la ATCC el 16 de julio de 2002. A los hibridomas se les han asignado los siguientes números de depósito:
Hibridoma N.º de depósito
3.1.1 (LN 15848) PTA-3600
7.1.2 (LN 15849) PTA-3601
10.8.3 (LN 15850) PTA-3602
15.1.1 (LN 15851) PTA-3603
21.4.1 (LN 15853) PTA-3605
- 21.2.1
- (LN 15874) PTA-4549
- 22.1.1
- (LN 15875) PTA-4550
- 23.5.1
- (LN 15855) PTA-4548
23.25.1 (LN 15876) PTA-4551
23.28.1 (LN 15877) PTA-4552
- 23.29.1
- (LN 15878) PTA-4553
- 24.2.1
- (LN 15879) PTA-4554
15 Las secuencias de estos anticuerpos son conocidas, y se describen en el documento WO 03/040170. Por conveniencia, se muestran a continuación las secuencias de aminoácidos de las cadenas pesadas y ligeras de dos de estos anticuerpos:
Anticuerpo 3.1.1:
- 3.1.1: Secuencia de proteína de cadena pesada
- Variable (SEQ ID NO: 1): Constante (SEQ ID NO: 2):
- 3.1.1: Secuencia de proteína de cadena ligera
- Variable (SEQ ID NO: 3): Constante (SEQ ID NO: 4):
5
- 3.1.1H-A78T-V88A-V97A: Secuencia de proteína de cadena pesada
- Variable (SEQ ID NO: 9): Constante (SEQ ID NO: 2):
- 3.1.1 L-L4M-L83V: Secuencia de proteína de cadena ligera
- Variable (SEQ ID NO: 10): Constante (SEQ ID NO: 4):
Anticuerpo 21.4.1:
- 21.4.1: Secuencia de proteína de cadena pesada
- Variable (SEQ ID NO: 5): Constante (SEQ ID NO: 6):
- 21.4.1: Secuencia de proteína de cadena ligera
- Variable (SEQ ID NO: 7): Constante (SEQ ID NO: 8):
6
5
15
25
35
45
55
Cuando se administra en combinación con un inhibidor de la replicación del ADN, por ejemplo, cisplatino, el anticuerpo se puede administrar antes, durante o después de la administración del inhibidor.
En un aspecto, la invención se refiere a una solución acuosa para inyección intravenosa, con el pH de aproximadamente 5,0 a 6,0, preferentemente pH de aproximadamente 5,5. Dicha solución se puede formular con acetato de sodio (trihidrato), ácido acético (glacial), polisorbato 80, cloruro de sodio y agua. Es preferente que la solución de anticuerpo se almacene a temperaturas de refrigeración de entre 2 ºC y 8 ºC, y no se congele.
También se divulgan procedimientos de tratamiento de un tumor en un paciente en necesidad de dicho tratamiento, que comprenden administrar a dicho paciente una combinación de una cantidad terapéuticamente eficaz de un anticuerpo agonista de CD40 y una cantidad terapéuticamente eficaz de un inhibidor de la replicación del ADN, por ejemplo, un derivado de platino. De acuerdo con la presente divulgación, un anticuerpo agonista de CD40 funciona en combinación sinérgica con el compuesto de derivado de platino, especialmente cisplatino, de modo que el efecto antitumoral de la combinación es mayor que el que podría predecirse a partir de la administración de cada compuesto solo.
Los derivados de platino son un grupo bien conocido de compuestos que muestran su actividad antitumoral interfiriendo con la replicación del ADN. De acuerdo con la presente divulgación, los derivados de platino se seleccionan del grupo que consiste en cisplatino (cis-diaminodicloroplatino, véase el índice de Merck), carboplatino y oxaliplatino.
La invención se describirá con referencia a los siguientes ejemplos.
Ejemplos
Ejemplo 1: Efectos del anticuerpo sobre células del ganglio linfático de pacientes con cáncer
Se examinaron los efectos de un anticuerpo humano anti-CD40 (21.4.1) sobre células del ganglio linfático obtenidas de pacientes con cáncer estimulados con células tumorales autólogas.
Se recogieron células y tumores de ganglios linfáticos de pacientes con carcinoma de células renales, cáncer de pulmón no microcítico, carcinoma de células de transición de vejiga, cáncer de colon, cáncer de próstata y cáncer de cabeza y cuello. Las células de ganglios linfáticos se colocaron en cultivo junto con tumores tratados con colagenasa irradiados (recuperados del mismo paciente) en presencia o ausencia de 21.4.1 (1 g/ml; 6,7 nM). Se evaluó la proliferación usando 3H-timidina 96 horas después. Se evaluó el número de células productoras de INFγ por ELISPOT, después de la reestimulación.
El anticuerpo potenció el número de linfocitos T positivos para IFNγ+ en cultivos de células de ganglios linfáticos estimuladas con antígeno tumoral. Además, la proliferación de estas células de ganglios linfáticos en respuesta al antígeno tumoral se potenció 3-4 veces.
El anticuerpo potenció la capacidad de proliferación y de producción de citocinas de las células de ganglios linfáticos obtenidas de pacientes con cáncer cuando se estimularon con el antígeno tumoral.
Ejemplo 2: Unión del anticuerpo al receptor Fc
Se examinó la unión de un anticuerpo anti-CD40 (21.4.1) a los receptores Fc en leucocitos humanos y de macaco de Java.
Estudios de citometría de flujo indicaron que se expresaban los tipos de FcR FcγRII (CD32) y FcγRIII (CD16) así como niveles muy bajos de FcγRI (CD64), en leucocitos humanos. Se determinó la unión de 21.4.1 a los receptores Fc (FcR) en leucocitos de sangre periférica humana o de macaco de Java usando 125 I-21.4.1 y un mAb de control de IgG1 humana. Se aislaron leucocitos humanos procedentes de donantes normales o leucocitos de macaco de Java a partir de sangre completa usando gel de plasma y se lavaron a fondo para permitir la disociación de las inmunoglobulinas séricas unidas al receptor. Se usó centrifugación a través de un colchón de sacarosa para separar anticuerpos de unidos a células y libres. Los estudios se realizaron a 4 ºC en presencia de azida de sodio para evitar la internalización del receptor.
Se sometió a prueba 21.4.1 para determinar la unión específica a FcR usando el anticuerpo compatible con el isotipo de IgG2 humana no marcado en exceso como competidor. La unión específica de 125 I-21.4.1 a FcR en leucocitos humanos (n = 5 donantes) fue de -1,08,5 %, y la unión específica a FcR en leucocitos de macaco de Java (n = 4) fue de un 1513 %. La adición de un exceso de 500 veces de 21.4.1 no marcado, que bloquearía cualquier unión específica de 125I-21.4.1 a receptores CD40 de leucocitos, así como FcR, demostró una unión específica de un 49 % y un 67 % de 125I-21.4.1 a receptores CD40 de leucocitos humanos y de macaco de Java, respectivamente (el % de unión específica a CD40 se calculó restando el % de unión a FcR del % total de unión específica). Como control, 125 I-IgG1 demostró consistentemente unión específica a leucocitos humanos y de macaco de Java. La unión específica del anticuerpo de control IgG1 a FcR en leucocitos humanos y de macaco de Java representó un 56 % y un 51 % de la radioactividad unida total, respectivamente.
Estos estudios indican que el anticuerpo muestra unión específica mínima a receptores Fc en leucocitos humanos y
8
Claims (1)
-
imagen1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53163903P | 2003-12-22 | 2003-12-22 | |
| US531639P | 2003-12-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2580002T3 true ES2580002T3 (es) | 2016-08-18 |
Family
ID=34738672
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10162787.5T Expired - Lifetime ES2580002T3 (es) | 2003-12-22 | 2004-12-09 | Formulación de anticuerpo contra CD40 y procedimientos |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US20050136055A1 (es) |
| EP (3) | EP2218461B1 (es) |
| JP (3) | JP2007515469A (es) |
| KR (2) | KR100847944B1 (es) |
| CN (2) | CN102552905A (es) |
| AU (1) | AU2004308749B2 (es) |
| BR (1) | BRPI0418029B8 (es) |
| CA (2) | CA2549652C (es) |
| DK (1) | DK2218461T3 (es) |
| ES (1) | ES2580002T3 (es) |
| HU (1) | HUE027717T2 (es) |
| IL (2) | IL175540A (es) |
| NO (1) | NO343797B1 (es) |
| NZ (2) | NZ583179A (es) |
| PL (1) | PL2218461T3 (es) |
| RU (1) | RU2355421C2 (es) |
| SI (1) | SI2218461T1 (es) |
| TW (1) | TWI359671B (es) |
| WO (1) | WO2005063289A1 (es) |
| ZA (1) | ZA200603804B (es) |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6946129B1 (en) | 1999-06-08 | 2005-09-20 | Seattle Genetics, Inc. | Recombinant anti-CD40 antibody and uses thereof |
| US7658924B2 (en) * | 2001-10-11 | 2010-02-09 | Amgen Inc. | Angiopoietin-2 specific binding agents |
| AU2006329944A1 (en) * | 2005-12-09 | 2007-07-05 | Seattle Genetics, Inc. | Methods of using CD40 binding agents |
| US7993648B2 (en) | 2006-05-03 | 2011-08-09 | The Regents of the Universitry of Colorado | Immunostimulatory regimen comprising administering type 1 interferon and agonistic anti-CD40 antibody |
| US20090074711A1 (en) * | 2006-09-07 | 2009-03-19 | University Of Southhampton | Human therapies using chimeric agonistic anti-human cd40 antibody |
| LT2176298T (lt) | 2007-05-30 | 2018-04-10 | Xencor, Inc. | Būdai ir kompozicijos, skirti cd32b ekspresuojančių ląstelių slopinimui |
| JO2913B1 (en) * | 2008-02-20 | 2015-09-15 | امجين إنك, | Antibodies directed towards angiopoietin-1 and angiopoietin-2 proteins and their uses |
| US20110311525A1 (en) * | 2008-08-29 | 2011-12-22 | Academisch Ziekenhuis Leiden H.O.D.N. Lumc | Delivery of a cd40 agonist to a tumor draining lymph node of a subject |
| US9561214B2 (en) * | 2008-10-16 | 2017-02-07 | Array Biopharma Inc. | Method of treatment using inhibitors of mitosis |
| WO2011101332A1 (en) | 2010-02-16 | 2011-08-25 | Proyecto De Biomedicina Cima, S.L. | Compositions based on the fibronectin extracellular domain a for the treatment of melanoma |
| WO2012123269A1 (en) | 2011-03-11 | 2012-09-20 | Proyecto De Biomedicina Cima, S.L. | Immunogenic compositions and methods for their use |
| EP2505640A1 (en) | 2011-03-29 | 2012-10-03 | Neo Virnatech, S.L. | Vaccine compositions for birnavirus-borne diseases |
| CN106928362B (zh) | 2011-04-29 | 2021-10-26 | 埃派斯进有限公司 | 抗-cd40抗体及其使用方法 |
| SG11201406592QA (en) | 2012-05-04 | 2014-11-27 | Pfizer | Prostate-associated antigens and vaccine-based immunotherapy regimens |
| FR2994390B1 (fr) | 2012-08-10 | 2014-08-15 | Adocia | Procede d'abaissement de la viscosite de solutions de proteines a concentration elevee |
| KR102270618B1 (ko) | 2012-10-30 | 2021-06-30 | 아펙시젠, 인코포레이티드 | 항-cd40 항체 및 사용 방법 |
| US9856319B2 (en) | 2012-12-28 | 2018-01-02 | Abbvie Inc. | Monovalent binding proteins |
| WO2014121099A1 (en) | 2013-01-31 | 2014-08-07 | Thomas Jefferson University | Agonist fusion protein for cd40 ox40 and uses thereof |
| EP3995507B1 (en) | 2013-08-08 | 2023-10-04 | Cytune Pharma | Il-15 and il-15ralpha sushi domain based on modulokines |
| KR20240073140A (ko) | 2014-10-29 | 2024-05-24 | 씨젠 인크. | 비-푸코실화된 항-cd40 항체의 용량 및 투여 |
| WO2017009842A2 (en) | 2015-07-16 | 2017-01-19 | Biokine Therapeutics Ltd. | Compositions and methods for treating cancer |
| PL3426271T3 (pl) | 2016-03-10 | 2025-11-24 | Cg Oncology, Inc. | Sposoby leczenia guzów litych terapią skojarzoną |
| PT3468997T (pt) | 2016-06-08 | 2023-12-07 | Debra Zack | Tratamento de doenças relacionadas com igg4 com anticorpos anti-cd19 com ligação cruzada a cd32b |
| 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 |
| WO2018085734A1 (en) | 2016-11-04 | 2018-05-11 | Memorial Sloan Kettering Cancer Center | Bi-specific activators for tumor therapy |
| KR102019033B1 (ko) * | 2016-11-11 | 2019-09-06 | 다이노나(주) | Cd40에 특이적으로 결합하는 항체 및 그의 용도 |
| WO2018162450A1 (en) | 2017-03-06 | 2018-09-13 | Fundación Para La Investigación Médica Aplicada | New inmunostimulatory compositions comprising an entity of cold inducible rna-binding protein with an antigen for the activation of dendritic cells |
| EP3632933A4 (en) * | 2017-06-01 | 2021-03-03 | Seoul National University R & DB Foundation | Novel anti-cd40 antibodies and use thereof |
| JP2020521788A (ja) * | 2017-06-02 | 2020-07-27 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | 免疫アゴニストの投与経路 |
| EP3418302A1 (en) * | 2017-06-19 | 2018-12-26 | F. Hoffmann-La Roche AG | Administration routes for immune agonists |
| AU2019255781A1 (en) * | 2018-04-20 | 2020-10-29 | Lyvgen Biopharma Holdings Limited | Anti-CD40 antibodies and uses thereof |
| CN112638375A (zh) | 2018-06-15 | 2021-04-09 | 旗舰创业创新五公司 | 通过后细胞信号传导因子的调节来增加免疫活性 |
| CA3114567A1 (en) * | 2018-09-28 | 2020-04-02 | Lyvgen Biopharma Co., Ltd. | Anti-cd40 binding molecules having engineered fc domains and therapeutic uses thereof |
| CN116063495A (zh) * | 2018-09-28 | 2023-05-05 | 礼进生物医药科技（上海）有限公司 | 具有经过工程化的Fc结构域的抗CD40结合分子及其治疗用途 |
| BR112021010414A2 (pt) * | 2018-11-30 | 2021-09-08 | Jiangsu Hengrui Medicine Co., Ltd. | Composição farmacêutica compreendendo um anticorpo cd40, método para preparar uma preparação liofilizada, preparação liofilizada, uso das mesmas e produto que compreende um recipiente contendo as mesmas |
| MX2021008305A (es) | 2019-01-11 | 2021-08-24 | Novartis Ag | Anticuerpos anti-cd40 para el uso en el tratamiento de hidradenitis supurativa. |
| EP3962493A2 (en) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity/level of irf or sting or of treating cancer, comprising the administration of a sting modulator and/or purinergic receptor modulator or postcellular signaling factor |
| BR112022010680A2 (pt) | 2019-12-03 | 2022-08-16 | Evotec Int Gmbh | Proteínas de ligação ao antígeno associado ao interferon e uso das mesmas |
| WO2021127217A1 (en) | 2019-12-17 | 2021-06-24 | Flagship Pioneering Innovations V, Inc. | Combination anti-cancer therapies with inducers of iron-dependent cellular disassembly |
| WO2021168274A1 (en) | 2020-02-21 | 2021-08-26 | Silverback Therapeutics, Inc. | Nectin-4 antibody conjugates and uses thereof |
| CN116234575A (zh) * | 2020-06-04 | 2023-06-06 | 赛尔疫苗私人有限公司 | 激动剂抗cd40抗体 |
| EP4172323A1 (en) | 2020-06-29 | 2023-05-03 | Flagship Pioneering Innovations V, Inc. | Viruses engineered to promote thanotransmission and their use in treating cancer |
| IL299508A (en) | 2020-07-01 | 2023-02-01 | Ars Pharmaceuticals Inc | Anti-asgr1 antibody conjugates and uses thereof |
| WO2022037662A1 (en) * | 2020-08-21 | 2022-02-24 | Wuxi Biologics (Shanghai) Co. Ltd. | Cd40 agonistic antibody and method of use |
| KR20230165276A (ko) | 2021-03-31 | 2023-12-05 | 플래그쉽 파이어니어링 이노베이션스 브이, 인크. | 타노트랜스미션 폴리펩티드 및 암의 치료에서의 이의 용도 |
| AU2022303363A1 (en) | 2021-06-29 | 2024-01-18 | Flagship Pioneering Innovations V, Inc. | Immune cells engineered to promote thanotransmission and uses thereof |
| US20240174732A1 (en) | 2022-10-05 | 2024-05-30 | Flagship Pioneering Innovations V, Inc. | Nucleic acid molecules encoding trif and additional polypeptides and their use in treating cancer |
| US20240269251A1 (en) | 2023-01-09 | 2024-08-15 | Flagship Pioneering Innovations V, Inc. | Genetic switches and their use in treating cancer |
Family Cites Families (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5247069A (en) * | 1986-06-13 | 1993-09-21 | Oncogen | Ligands and methods for augmenting B-cell proliferation |
| JP2547556B2 (ja) * | 1987-02-06 | 1996-10-23 | 株式会社 ミドリ十字 | ｒ−グロブリンの液状製剤 |
| SE8701004D0 (sv) | 1987-03-11 | 1987-03-11 | Astra Ab | Method for therapy of leukemias and certain other malignancies |
| JPH03204821A (ja) * | 1989-12-28 | 1991-09-06 | Green Cross Corp:The | モノクローナル抗体含有水溶液の加熱処理方法 |
| CA2089229C (en) * | 1992-02-14 | 2010-04-13 | Alejandro A. Aruffo | Cd40cr receptor and ligands therefor |
| AU5098493A (en) | 1992-08-21 | 1994-03-15 | Schering Corporation | Cd40 ligand, anti cd40 antibodies, and soluble cd40 |
| EP0724456B1 (en) * | 1993-10-01 | 2003-12-10 | Immunex Corporation | Antibodies to cd40 |
| AU680102B2 (en) * | 1993-12-23 | 1997-07-17 | Immunex Corporation | Method of preventing or treating disease characterized by neoplastic cells expressing CD40 |
| GB9425060D0 (en) | 1994-12-13 | 1995-02-08 | Univ Birmingham | Carcinoma treatment |
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| JP3919235B2 (ja) * | 1997-06-13 | 2007-05-23 | ジェネンテク，インコーポレイテッド | 抗体製剤 |
| GEP20063774B (en) * | 1999-06-01 | 2006-03-27 | Biogen Idec Inc | Blocking Monoclonal Antibody to VLA-1 and Its Use for Treatment of Inflammatory Disorders |
| JP4516711B2 (ja) * | 1999-12-28 | 2010-08-04 | 中外製薬株式会社 | 安定な抗体組成物及び注射製剤 |
| US6358670B1 (en) * | 1999-12-28 | 2002-03-19 | Electron Vision Corporation | Enhancement of photoresist plasma etch resistance via electron beam surface cure |
| WO2001056603A1 (en) | 2000-02-01 | 2001-08-09 | Tanox, Inc. | Cd40-binding apc-activating molecules |
| KR20020091170A (ko) * | 2000-03-31 | 2002-12-05 | 아이덱 파마슈티칼즈 코포레이션 | Ｂ 세포 림프종의 치료를 위한 항-사이토카인 항체 또는길항제 및 항-ｃｄ２０의 조합된 사용 |
| US6838250B2 (en) | 2000-03-31 | 2005-01-04 | Ortho-Clinical Diagnostics, Inc. | Immunoassay for C-reactive protein |
| US20030059427A1 (en) | 2000-04-28 | 2003-03-27 | Force Walker R. | Isolation and characterization of highly active anti-CD40 antibody |
| US7063845B2 (en) * | 2000-04-28 | 2006-06-20 | Gemini Science, Inc. | Human anti-CD40 antibodies |
| US7015194B2 (en) * | 2000-05-10 | 2006-03-21 | Novo Nordisk A/S | Pharmaceutical composition comprising factor VIIa and anti-TFPI |
| DE60143535D1 (de) * | 2000-10-02 | 2011-01-05 | Novartis Vaccines & Diagnostic | Humane antikörper gegen cd40 |
| IL155002A0 (en) * | 2000-10-12 | 2003-10-31 | Genentech Inc | Reduced-viscosity concentrated protein formulations |
| IL149701A0 (en) * | 2001-05-23 | 2002-11-10 | Pfizer Prod Inc | Use of anti-ctla-4 antibodies |
| CA2454587C (en) * | 2001-07-25 | 2012-11-13 | Protein Design Labs, Inc. | Stable lyophilized pharmaceutical formulation of igg antibodies |
| IL161677A0 (en) * | 2001-11-08 | 2004-09-27 | Protein Design Labs | Stable liquid pharmaceutical formulation of igg antibodies |
| AR039067A1 (es) * | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| ATE395413T1 (de) * | 2001-12-03 | 2008-05-15 | Amgen Fremont Inc | Antikörperkategorisierung auf der grundlage von bindungseigenschaften |
| US7115108B2 (en) | 2002-04-02 | 2006-10-03 | Becton, Dickinson And Company | Method and device for intradermally delivering a substance |
| US20080009439A1 (en) * | 2002-11-05 | 2008-01-10 | Alsobrook John P | Compositions and Methods of Use for a Fibroblast Growth Factor |
| HN2004000285A (es) * | 2003-08-04 | 2006-04-27 | Pfizer Prod Inc | ANTICUERPOS DIRIGIDOS A c-MET |
-
2004
- 2004-12-02 US US11/001,980 patent/US20050136055A1/en not_active Abandoned
- 2004-12-09 CN CN2012100028652A patent/CN102552905A/zh active Pending
- 2004-12-09 DK DK10162787.5T patent/DK2218461T3/en active
- 2004-12-09 HU HUE10162787A patent/HUE027717T2/en unknown
- 2004-12-09 NZ NZ583179A patent/NZ583179A/en not_active IP Right Cessation
- 2004-12-09 AU AU2004308749A patent/AU2004308749B2/en not_active Ceased
- 2004-12-09 PL PL10162787.5T patent/PL2218461T3/pl unknown
- 2004-12-09 CN CNA2004800385418A patent/CN1897971A/zh active Pending
- 2004-12-09 WO PCT/IB2004/004103 patent/WO2005063289A1/en not_active Ceased
- 2004-12-09 KR KR1020067012364A patent/KR100847944B1/ko not_active Expired - Fee Related
- 2004-12-09 EP EP10162787.5A patent/EP2218461B1/en not_active Expired - Lifetime
- 2004-12-09 RU RU2006120950/14A patent/RU2355421C2/ru active
- 2004-12-09 CA CA2549652A patent/CA2549652C/en not_active Expired - Lifetime
- 2004-12-09 CA CA2704300A patent/CA2704300A1/en not_active Abandoned
- 2004-12-09 NZ NZ547162A patent/NZ547162A/en not_active IP Right Cessation
- 2004-12-09 BR BRPI0418029A patent/BRPI0418029B8/pt not_active IP Right Cessation
- 2004-12-09 KR KR1020087004912A patent/KR20080023766A/ko not_active Ceased
- 2004-12-09 ES ES10162787.5T patent/ES2580002T3/es not_active Expired - Lifetime
- 2004-12-09 EP EP04801378A patent/EP1706143A1/en not_active Ceased
- 2004-12-09 JP JP2006546357A patent/JP2007515469A/ja active Pending
- 2004-12-09 SI SI200432321A patent/SI2218461T1/sl unknown
- 2004-12-09 EP EP16164228.5A patent/EP3081933A1/en not_active Withdrawn
- 2004-12-21 TW TW093139794A patent/TWI359671B/zh not_active IP Right Cessation
-
2006
- 2006-05-10 IL IL175540A patent/IL175540A/en active IP Right Grant
- 2006-05-12 ZA ZA200603804A patent/ZA200603804B/en unknown
- 2006-07-20 NO NO20063373A patent/NO343797B1/no not_active IP Right Cessation
-
2009
- 2009-07-14 US US12/502,587 patent/US20090311254A1/en not_active Abandoned
- 2009-10-11 IL IL201409A patent/IL201409A0/en unknown
-
2010
- 2010-12-23 US US12/978,272 patent/US20110104182A1/en not_active Abandoned
-
2011
- 2011-04-28 JP JP2011100868A patent/JP5634321B2/ja not_active Expired - Fee Related
-
2012
- 2012-03-19 US US13/424,260 patent/US20120263732A1/en not_active Abandoned
-
2014
- 2014-06-12 JP JP2014121342A patent/JP2014205692A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2580002T3 (es) | Formulación de anticuerpo contra CD40 y procedimientos | |
| US11059876B2 (en) | IL-15 variants and uses thereof | |
| US20210214436A1 (en) | Multi-specific binding proteins and improvements thereon | |
| ES2963598T3 (es) | Dominios de unión al antígeno humanizado contra CD19 y métodos de uso | |
| DE69433820T2 (de) | Verwendung von löslichen oligomerischen cd40 liganden oder monoklonalen antikörpern zur herstellung eines arzneimitells zur vorbeugung oder behandlung von neoplastischen krankheiten | |
| KR102602329B1 (ko) | Cd3에 특이적인 항체 및 이의 용도 | |
| CN102271711B (zh) | 每种维持移植物抗肿瘤效应的免疫重建促进剂或感染预防剂 | |
| US20240199756A1 (en) | Bispecific antibodies targeting nkp46 and cd38 and methods of use thereof | |
| WO2021129775A1 (zh) | 抗ctla-4单克隆抗体及其制备方法与应用 | |
| CN115151565A (zh) | 包含抗CD19抗体和γδT细胞的抗肿瘤组合疗法 | |
| US12331127B2 (en) | Therapeutic uses of anti-GITR antibodies | |
| US20230014026A1 (en) | Anti-Tumor Combination Therapy comprising Anti-CD19 Antibody and Polypeptides Blocking the SIRPalpha-CD47 Innate Immune Checkpoint | |
| CN114786723A (zh) | 序贯抗cd19疗法 | |
| CN110831622A (zh) | Fgl2单克隆抗体及其在治疗恶性肿瘤中的用途 | |
| KR20240024074A (ko) | 암의 치료 및/또는 예방을 위한 의약품 | |
| KR20240019073A (ko) | Nkp46 및 gpc3를 표적으로 하는 이중 특이적 항체 및 이의 사용 방법 | |
| HK40081595B (zh) | 三特异性抗体及其用途 | |
| EA046081B1 (ru) | Мультиспецифические связывающие белки и их усовершенствования | |
| MXPA06006153A (es) | Formulacion y metodos del anticuerpo de cd40 |