Combination therapy for neoplasia treatment

Patent metadata

Field	Value
Publication number	US-2016199488-A1
Application number	US-201514946067-A
Country	US
Kind code	A1
Filing date	Nov 19, 2015
Priority date	Mar 7, 2013
Publication date	Jul 14, 2016
Grant date	—

Abstract

The present invention relates to an insulin-like growth factor (IGF) receptor antagonist for use in the treatment of prostate neoplasia, including benign prostatic hyperplasia (BPH), prostate cancer, and particularly CRPC, wherein the antagonist is used in combination with an androgen receptor antagonist. An embodiment of the invention is where the androgen receptor antagonist is enzalutamide.

First claim

1 . A method of treatment of prostate neoplasia comprising administering a therapeutically effective amount of an IGF receptor antagonist which is an antibody which binds to IGF ligand and reduces or blocks binding of IGF ligand to its receptor to a patient in need thereof, and additionally administering a therapeutically effective amount of an androgen receptor antagonist to the same patient within seven days before or after administration of the IGF receptor antagonist.

2 . The method of claim 1 wherein the prostate neoplasia, is benign prostatic hyperplasia (BPH) or prostate cancer.

3 . The method of claim 2 wherein the prostate cancer, is castration resistent prostate cancer.

4 . The method of claim 1 wherein the antibody is an antibody having heavy chain complementary determining regions of SEQ ID NO: 1 (HCDR1), SEQ ID NO: 2 (HCDR2), and SEQ ID NO: 3 (HCDR3) and light chain determining regions of SEQ ID NO: 4 (LCDR1), SEQ ID NO: 5 (LCDR2), and SEQ ID NO: 6 (LCDR3), or an antibody having heavy chain complementary determining regions of SEQ ID NO: 11 (HCDR1), SEQ ID NO: 12 (HCDR2), and SEQ ID NO: 13 (HCDR3) and light chain determining regions of SEQ ID NO: 14 (LCDR1), SEQ ID NO: 15 (LCDR2), and SEQ ID NO: 16 (LCDR3), or an antibody having heavy chain complementary determining regions of SEQ ID NO: 21 (HCDR1), SEQ ID NO: 22 (HCDR2), and SEQ ID NO: 23 (HCDR3) and light chain determining regions of SEQ ID NO: 24 (LCDR1), SEQ ID NO: 25 (LCDR2), and SEQ ID NO: 26 (LCDR3), or an antibody having heavy chain complementary determining regions of SEQ ID NO: 31 (HCDR1), SEQ ID NO: 32 (HCDR2), and SEQ ID NO: 33 (HCDR3) and light chain determining regions of SEQ ID NO: 34 (LCDR1), SEQ ID NO: 35 (LCDR2), and SEQ ID NO: 36 (LCDR3), or an antibody having a heavy chain variable region of SEQ ID NO: 7 and a light chain variable region of SEQ ID NO: 8, or an antibody having a heavy chain variable region of SEQ ID NO: 17 and a light chain variable region of SEQ ID NO: 18, or an antibody having a heavy chain variable region of SEQ ID NO: 27 and a light chain variable region of SEQ ID NO: 28, or an antibody having a heavy chain variable region of SEQ ID NO: 37 and a light chain variable region of SEQ ID NO: 38, or an antibody having a heavy chain variable region of SEQ ID NO: 41 and a light chain variable region of SEQ ID NO: 42, or an antibody having a heavy chain variable region of SEQ ID NO: 43 and a light chain variable region of SEQ ID NO: 44, or an antibody having a heavy chain of SEQ ID NO: 9, and a light chain of SEQ ID NO: 10, or an antibody having a heavy chain of SEQ ID NO: 19, and a light chain of SEQ ID NO: 20, or an antibody having a heavy chain of SEQ ID NO: 29, and a light chain of SEQ ID NO: 30, or an antibody having a heavy chain of SEQ ID NO: 39, and a light chain of SEQ ID NO: 40, or an antibody having a heavy chain of SEQ ID NO: 45, and a light chain of SEQ ID NO: 46.

5 . The method of claim 4 wherein the antibody has a heavy chain of SEQ ID NO: 39, and a light chain of SEQ ID NO: 40.

6 . The method of claim 1 wherein the androgen receptor antagonist is an anti-androgen, an androgen synthesis inhibitor, a 17 α-hydroxylase/C17, 20 lyase (CYP17A1) inhibitor, a 5-alpha-reductase inhibitor, a corticosteroid, a luteinizing hormone-releasing hormone (LH-RH) agonist, or an estrogen agonist.

7 . The method of claim 6 , wherein the androgen receptor antagonist is flutamide, nilutamide, enzalutamide, bicalutamide, ketonazole, abiraterone, abiraterone acetate, orteronel, finasteride, dutasteride, bexlosteride, izonsteride, turosteride, episteride, dexamethasone, prednisone, leuprolide, goserelin, triptorelin, histrelin, or estrogen.

8 . A method of treatment of prostate neoplasia comprising administering a therapeutically effective amount of an IGF ligand antibody having heavy chain complementary determining regions of SEQ ID NO: 31 (HCDR1), SEQ ID NO: 32 (HCDR2), and SEQ ID NO: 33 (HCDR3) and light chain determining regions of SEQ ID NO: 34 (LCDR1), SEQ ID NO: 35 (LCDR2), and SEQ ID NO: 36 (LCDR3) to a patient in need thereof, and additionally administering a therapeutically effective amount of enzalutamide within seven days before or after administration of the IGF receptor antagonist.

9 . The method of claim 8 wherein the antibody has a heavy chain of SEQ ID NO: 39, and a light chain of SEQ ID NO: 40.

10 . A method of treatment of prostate neoplasia comprising administering a therapeutically effective amount of an IGF ligand antibody having heavy chain complementary determining regions of SEQ ID NO: 31 (HCDR1), SEQ ID NO: 32 (HCDR2), and SEQ ID NO: 33 (HCDR3) and light chain determining regions of SEQ ID NO: 34 (LCDR1), SEQ ID NO: 35 (LCDR2), and SEQ ID NO: 36 (LCDR3) to a patient in need thereof, and additionally administering a therapeutically effective amount of abiraterone within seven days before or after administration of the IGF receptor antagonist.

11 . The method of claim 10 wherein the antibody has a heavy chain of SEQ ID NO: 39, and a light chain of SEQ ID NO: 40.

Assignees

• Boehringer Ingelheim Int

Inventors

• Adam Paul
• Friedbichler Katrin

Classifications

• C07K16/2863 Primary

  against receptors for growth factors, growth regulators · CPC title

• A61P5/28

  Antiandrogens · CPC title

• A61K39/39558 Primary

  against tumor tissues, cells, antigens · CPC title

• A61P5/44

  Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title