Combination of human anti-FGFR4 antibody and Sorafenib

Patent metadata

Field	Value
Publication number	US-10995143-B2
Application number	US-201716076776-A
Country	US
Kind code	B2
Filing date	Feb 9, 2017
Priority date	Feb 10, 2016
Publication date	May 4, 2021
Grant date	May 4, 2021

Abstract

The present invention relates to the medical use of antibodies against the FGF receptor 4 (FGFR4) combined with Sorafenib, in particular for the prevention or treatment of hyperproliferative diseases associated with FGFR expression, overexpression or hyperactivity.

First claim

The invention claimed is:

1. A method for the treatment of hepatocellular carcinoma (HCC), said method comprising administering an effective amount of a combination of (i) a human anti-FGFR4 antibody or an antigen-binding fragment of said antibody, and (ii) Sorafenib or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is directed against an epitope between amino acids 119-248 of human FGFR4 (SEQ ID NO: 70), and comprises:
(i) a heavy chain comprising:
(a) a CDRH1 as shown in SEQ ID NO: 3,
(b) a CDRH2 as shown in SEQ ID NO: 8, and
(c) a CDRH3 as shown in SEQ ID NO: 15,

and a light chain comprising:
(d) a CDRL1 as shown in SEQ ID NO: 23,
(e) a CDRL2 as shown in SEQ ID NO: 25, and
(f) a CDRL3 as shown in SEQ ID NO: 30;

or
(ii) a heavy chain comprising:
(a) a CDRH1 as shown in SEQ ID NO: 3,
(b) a CDRH2 as shown in SEQ ID NO: 8, and
(c) a CDRH3 as shown in SEQ ID NO: 15,

and a light chain comprising:
(d) a CDRL1 as shown in SEQ ID NO: 68,
(e) a CDRL2 as shown in SEQ ID NO: 27, and
(f) a CDRL3 as shown in SEQ ID NO: 35.

2. The method of claim 1 , wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is a Fab fragment, a Fab′ fragment, a F(ab′), fragment, a Fv fragment, a diabody, or a single chain antibody molecule.

3. The method of claim 1 , wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is of the IgG1-, IgG2-, IgG3- or IgG4-type.

4. The method of claim 1 , said method further comprising chemotherapy or radiation.

5. The method of claim 1 , wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is coupled to a labeling group or to an effector group.

6. The method of claim 1 , wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is fused to IL-2.

7. A method for the treatment of hepatocellular carcinoma (HCC), said method comprising administering an effective amount of a combination of (i) a human anti-FGFR4 antibody or an antigen-binding fragment of said antibody, and (ii) Sorafenib or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is directed against an epitope between amino acids 119-248 of human FGFR4 (SEQ ID NO: 70), and comprises:
a heavy chain comprising:
(a) a CDRH1 as shown in SEQ ID NO: 3,
(b) a CDRH2 as shown in SEQ ID NO: 8, and
(c) a CDRH3 as shown in SEQ ID NO: 15,

and a light chain comprising:
(d) a CDRL1 as shown in SEQ ID NO: 23,
(e) a CDRL2 as shown in SEQ ID NO: 25, and
(f) a CDRL3 as shown in SEQ ID NO: 30.

8. A method for the treatment of hepatocellular carcinoma (HCC), said method comprising administering an effective amount of a combination of (i) a human anti-FGFR4 antibody or an antigen-binding fragment of said antibody, and (ii) Sorafenib or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein the human anti-FGFR4 antibody or the antigen-binding fragment of said antibody is directed against an epitope between amino acids 119-248 of human FGFR4 (SEQ ID NO: 70), and comprises:
a heavy chain comprising:
(a) a CDRH1 as shown in SEQ ID NO: 3,
(b) a CDRH2 as shown in SEQ ID NO: 8, and
(c) a CDRH3 as shown in SEQ ID NO: 15,
and a light chain comprising:
(d) a CDRL1 as shown in SEQ ID NO: 68,
(e) a CDRL2 as shown in SEQ ID NO: 27, and
(f) a CDRL3 as shown in SEQ ID NO: 35.

Assignees

• Daiichi Sankyo Europe Gmbh
• Daiichi Sankyo Co Ltd

Inventors

• Abraham Reimar
• Fukuchi Keisuke

Classifications

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• A61K31/44

  Non condensed pyridines; Hydrogenated derivatives thereof · CPC title

• A61K38/20

  Interleukins [IL] · CPC title

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• A61K39/3955

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title