Anti-GITR Antibodies and Methods of Use Thereof

• US 20180244793A1
• Filed: 04/25/2018
• Published: 08/30/2018
• Est. Priority Date: 05/28/2014
• Status: Abandoned Application

• Current Assignee: Agenus Inc., Ludwig Institute for Cancer Research, Ltd., Memorial Sloan-Kettering Cancer Center
• Original Assignee: Agenus Inc., Ludwig Institute for Cancer Research, Ltd., Memorial Sloan-Kettering Cancer Center
• Inventors: GONZALEZ, Ana M., WILSON, Nicholas S., UNDERWOOD, Deninis J., SEIBERT, Volker, LEGER, Olivier, VAN DIJK, Marc, ZAPPASODI, Roberta, MERGHOUB, Taha, WOLCHOK, Jedd David, SCHAER, David, RITTER, Gerd, TSUJI, Takemasa
• Application Number:
  US15/962,667
• Publication Number:
  US 20180244793A1
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 31/22 for herpes viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2809 : against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2878 : against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/34 : Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 : Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/75 : Agonist effect on antigen
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2333/70578 : NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30 CD40 or CD95 NGF-receptor G01N2333/71, TNF-receptor G01N2333/7151
• CPC Class Codes: G01N 33/502 : for testing non-proliferative effects
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Claims

1-205. -205. (canceled)

206. An isolated antibody that specifically binds to human GITR, comprising:

(a) a heavy chain variable region (VH) comprising a VH CDR1 comprising the amino acid sequence of DYAMY (SEQ ID NO;

     13),

a VH CDR2 comprising the amino acid sequence of VIRTYSGDVTYNQKFKD (SEQ ID NO;

     14), and

a VH CDR3 comprising the amino acid sequence of SGTVRGFAY (SEQ ID NO;

     15); and

(b) a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of KSSQSLLNSGNQKNYLT (SEQ ID NO;

     16),

a VL CDR2 comprising the amino acid sequence of WASTRES (SEQ ID NO;

     17), and

a VL CDR3 comprising the amino acid sequence of QNDYSYPYT (SEQ ID NO;

     18).

207. The antibody of claim 206, wherein the VH comprises the amino acid sequence of SEQ ID NO:

206.

208. The antibody of claim 206, wherein the VL comprises the amino acid sequence of SEQ ID NO:

208.

209. The antibody of claim 206, wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO;

206; and

(b) the VL comprises the amino acid sequence of SEQ ID NO;

208.

210. The antibody of claim 209, wherein:

(a) the amino acid sequence of the VH consists of the amino acid sequence of SEQ ID NO;

206; and

(b) the amino acid sequence of the VL consists of the amino acid sequence of SEQ ID NO;

208.

211. The antibody of claim 209, wherein the antibody further comprises a human immunoglobulin IgG₁ heavy chain constant region.

212. The antibody of claim 211, wherein the antibody further comprises a human immunoglobulin IgG kappa light chain constant region.

213. The antibody of claim 209, wherein the antibody further comprises a human immunoglobulin IgG kappa light chain constant region.

214. The antibody of claim 206, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

567.

215. The antibody of claim 214, wherein the VL comprises the amino acid sequence of SEQ ID NO:

208.

216. The antibody of claim 206, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:

576.

217. The antibody of claim 216, wherein the VH comprises the amino acid sequence of SEQ ID NO:

206.

218. The antibody of claim 206, wherein the antibody is produced by culturing a host cell comprising a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:

206 so that the nucleic acid molecule is expressed and the antibody is produced.

219. The antibody of claim 218, wherein the host cell further comprises a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:

576.

220. The antibody of claim 206, wherein the antibody is produced by culturing a host cell comprising a nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:

576 so that the nucleic acid molecule is expressed and the antibody is produced.

221. An isolated antibody that specifically binds to human GITR, wherein the antibody is produced by culturing a host cell comprising a first nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:

206 and a second nucleic acid molecule encoding the amino acid sequence of SEQ ID NO;

208 so that the first nucleic acid molecule and the second nucleic acid molecule are expressed and the antibody is produced.

222. The antibody of claim 221, wherein the host cell is a CHO cell.

223. The antibody of claim 222, wherein the first nucleic acid molecule and the second nucleic acid molecule are in a single vector.

224. The antibody of claim 222, wherein the first nucleic acid molecule is in a first vector and the second nucleic acid molecule is in a second vector.

225. An isolated antibody that specifically binds to human GITR, comprising:

(a) a heavy chain comprising the amino acid sequence of SEQ ID NO;

567; and

(b) a light chain comprising the amino acid sequence of SEQ ID NO;

576.

226. The antibody of claim 225, wherein:

(a) the amino acid sequence of the heavy chain consists of the amino acid sequence of SEQ ID NO;

567; and

(b) the amino acid sequence of the light chain consists of the amino acid sequence of SEQ ID NO;

576.

227. A pharmaceutical composition comprising:

an isolated antibody that specifically binds to human GITR, comprising;

(a) a heavy chain variable region (VH) comprising a VH CDR1 comprising the amino acid sequence of DYAMY (SEQ ID NO;

     13),

a VH CDR2 comprising the amino acid sequence of VIRTYSGDVTYNQKFKD (SEQ ID NO;

     14), and

a VH CDR3 comprising the amino acid sequence of SGTVRGFAY (SEQ ID NO;

     15); and

(b) a light chain variable region (VL) comprising a VL CDR1 comprising the amino acid sequence of KSSQSLLNSGNQKNYLT (SEQ ID NO;

     16),

a VL CDR2 comprising the amino acid sequence of WASTRES (SEQ ID NO;

     17), and

a VL CDR3 comprising the amino acid sequence of QNDYSYPYT (SEQ ID NO;

     18); and

a pharmaceutically acceptable carrier or excipient.

228. The pharmaceutical composition of claim 227, wherein:

(a) the VH comprises the amino acid sequence of SEQ ID NO;

206; and

(b) the VL comprises the amino acid sequence of SEQ ID NO;

208.

229. The pharmaceutical composition of claim 228, wherein the antibody further comprises a human immunoglobulin IgG₁ heavy chain constant region.

230. The pharmaceutical composition of claim 229, wherein the antibody further comprises a human immunoglobulin IgG kappa light chain constant region.

231. The pharmaceutical composition of claim 228, wherein the antibody further comprises a human immunoglobulin IgG kappa light chain constant region.

232. The pharmaceutical composition of claim 227, wherein:

(a) the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO;

567; and

(b) the VL comprises the amino acid sequence of SEQ ID NO;

208.

233. The pharmaceutical composition of claim 227, wherein:

(a) the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO;

576; and

(b) the VH comprises the amino acid sequence of SEQ ID NO;

206.

234. The pharmaceutical composition of claim 227, wherein the antibody is produced by culturing a host cell comprising a first nucleic acid molecule encoding the amino acid sequence of SEQ ID NO:

206 and a second nucleic acid molecule encoding the amino acid sequence of SEQ ID NO;

208 so that the first nucleic acid molecule and the second nucleic acid molecule are expressed and the antibody is produced.

235. The pharmaceutical composition of claim 234, wherein the host cell is a CHO cell.