Neutralizing prolactin receptor antibodies and their therapeutic use

Patent metadata

Field	Value
Publication number	US-9241989-B2
Application number	US-201013514996-A
Country	US
Kind code	B2
Filing date	Nov 18, 2010
Priority date	Dec 10, 2009
Publication date	Jan 26, 2016
Grant date	Jan 26, 2016

Abstract

The present invention is directed to the neutralizing prolactin receptor antibody 005-C04, as well as maturated forms thereof, and antigen binding fragments, pharmaceutical compositions containing them and their use in the treatment or prevention of benign disorders and indications mediated by the prolactin receptor such as endometriosis, adenomyosis, non-hormonal female contraception, benign breast disease and mastalgia, lactation inhibition, benign prostate hyperplasia, fibroids, hyper- and normoprolactinemic hair loss, and cotreatment in combined hormone therapy to inhibit mammary epithelial cell proliferation. The antibodies of the invention block prolactin receptor-mediated signaling.

First claim

The invention claimed is:

1. Antibody 005-C04, 005-C04-10-3, 005-C04-11-5, 005-C04-18-10-2, 005-C04-18-10-4, 005-C04-19-2, 005-C04-2-2, 005-C04-2-7, 005-C04-20-12-7, 005-C04-20-2, 005-C04-21-1, 005-C04-21-2, 005-C04-25-6, 005-C04-29-0, 005-C04-29-17-0, 005-C04-29-17-2, 005-C04-29-17-3, 005-C04-29-17-7, 005-C04-35-3, 005-C04-36-0, 005-C04-37-2, 005-C04-37-7, 005-C04-4-3-7, 005-C04-40-4, 005-C04-41-2, 005-C04-42-1, 005-C04-44-25-1, 005-C04-45-1, 005-C04-46-0, 005-C04-46-1, 005-C04-47-3, 005-C04-48-1, 005-C04-5-5, 005-C04-50-28-3, 005-C04-50-28-7, 005-C04-51-29-0, 005-C04-52-29-0, 005-C04-52-29-7, 005-C04-53-31-7, 005-C04-55-32-0, 005-C04-58-33-1, 005-C04-8-2, 005-C04-8-6, 005-C04-9-2, 005-C04-L2-1-11-0, 005-C04-L2-1-11-3, 005-C04-L2-1-12-2, 005-C04-L2-1-12-4, 005-C04-L2-1-16-4, 005-C04-L2-1-16-5, 005-C04-L2-1-2-3, 005-C04-L2-1-20-0, 005-C04-L2-1-20-1, 005-C04-L2-1-21-7, 005-C04-L2-1-23-7, 005-C04-L2-1-25-0, 005-C04-L2-1-25-4, 005-C04-L2-1-25-5, 005-C04-L2-1-25-7, 005-C04-L2-1-28-7, 005-C04-L2-1-3-2, 005-C04-L2-1-31-4, 005-C04-L2-1-31-7, 005-C04-L2-1-32-4, 005-C04-L2-1-33-7, 005-C04-L2-1-36-6, 005-C04-L2-1-38-3, 005-C04-L2-1-4-5, 005-C04-L2-1-40-2, 005-C04-L2-1-40-7, 005-C04-L2-1-42-0, 005-C04-L2-1-47-0, or 005-C04-L2-1-48-3 or antigen-binding fragments thereof.

2. Antibody or antigen-binding fragments according to claim 1 whereby the antibodies antagonize prolactin receptor-mediate signaling in human and mouse.

3. Antibody or antigen-binding fragment wherein
a. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12 and 17 and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, and 33, or
b. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 104, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
c. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 105, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or
d. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 139, 33; or
e. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 141, 33; or
f. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 106, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or
g. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 106, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
h. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 108, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 137, 28, 33; or
i. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 138, 33; or
j. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 114, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or
k. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 104, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
l. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 111, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or
m. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
n. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 118, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or
o. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 143; or
p. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 145; or
q. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 144; or
r. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 146; or
s. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 110, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
t. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 110, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or
u. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 127, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or
v. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 127, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 141, 33; or
w. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 6, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or
x. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 117, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
y. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or
z. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 115, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 138, 33; or
aa. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 12, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 23, 28, 33; or
bb. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 139, 33; or
cc. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 116, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
dd. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 107, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 140, 33; or
ee. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 103, 108, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or
ff. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 119, 17, and the variable light chain contains the CDR sequences corresponding to SEQ ID NO: 136, 28, 33; or
gg. the variable heavy chain contains the CDR sequences corresponding to SEQ ID NO: 102, 133,

Assignees

• Otto Christiane
• Wolf Siegmund
• Freiberg Christoph
• Harrenga Axel
• Greven Simone
• Trautwein Mark
• Bruder Sandra
• Eicker Andrea
• Wilmen Andreas
• Bayer Ip Gmbh

Inventors

• Otto Christiane
• Wolf Siegmund
• Freiberg Christoph
• Harrenga Axel
• Greven Simone
• Trautwein Mark
• Bruder Sandra
• Eicker Andrea
• Wilmen Andreas

Classifications

• A61P5/08

  for decreasing, blocking or antagonising the activity of the anterior pituitary hormones · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P5/24

  of the sex hormones · CPC title

• A61P5/30

  Oestrogens · CPC title

• A61P5/10

  of the posterior pituitary hormones, e.g. oxytocin, ADH · CPC title