US 2017/0253665 A1 · ANTIBODIES AGAINST CD73

Antibodies against cd73

AssigneeBristol-Myers Squibb Company

InventorsNils LONBERG, Alan J. KORMAN, Bryan C. BARNHART, Aaron P. YAMNIUK, Mohan SRINIVASAN, Karla A. HENNING, Ming LEI, Emanuela SEGA, Angela GOODENOUGH, Maria N. JURE-KUNKEL, Guodong CHEN, John S. SACK, Richard HUANG, Martin J. CORBETT, Joseph E. MYERS, JR., Liang SCHWEIZER, Sandra V. HATCHER, Haichun HUANG, Pingping ZHANG

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Abstract

The present invention provides isolated monoclonal antibodies, particularly human antibodies, that bind to human Cluster of Differentiation 73 (CD73) with high affinity, and inhibit the activity of CD73, and optionally mediate antibody dependent CD73 internalization. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided. Immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies of the invention are also provided. The invention also provides methods for inhibiting the growth of a tumor cell expressing CD73 using the antibodies of the invention, including methods for treating various cancers.

Claims36

Dependent claims

1-8. (canceled)

An isolated nucleic acid molecule encoding the heavy and light chains of an antibody which binds to human CD73, wherein the heavy and light chains respectively comprise:

(a) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
5, 6, and 7, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
9, 10, and 11, respectively;
(b) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
5, 6, and 7, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
13, 14, and 15, respectively;
(c) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
21, 22, and 23, respectively;
(d) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
25, 26, and 27, respectively;
(e) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
29, 30, and 31, respectively;
(f) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
33, 34, and 35, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
37, 38, and 39, respectively;
(g) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
41, 42, and 43, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
45, 46, and 47, respectively;
(h) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
41, 42, and 43, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
49, 50, and 51, respectively;
(i) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
53, 54, and 55, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
57, 58, and 59, respectively;
(j) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
61, 62, and 63, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
65, 66, and 67, respectively;
(k) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
69, 70, and 71, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
73, 74, and 75, respectively;
(l) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
69, 70, and 71, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
77, 78, and 79, respectively;
(m) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
81, 82, and 83, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
85, 86, and 87, respectively;
or
(n) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
89, 90, and 91, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
93, 94, and 95, respectively.

40 more elements

A composition comprising a nucleic acid molecule encoding the heavy chain of an antibody binding to human CD73, and a nucleic acid molecule encoding the light chain of the antibody binding to human CD73, and a pharmaceutical carrier, wherein the heavy and light chains respectively comprise:

(a) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
5, 6, and 7, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
9, 10, and 11, respectively;
(b) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
5, 6, and 7, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
13, 14, and 15, respectively;
(c) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
21, 22, and 23, respectively;
(d) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
25, 26, and 27, respectively;
(e) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
29, 30, and 31, respectively;
(f) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
33, 34, and 35, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
37, 38, and 39, respectively;
(g) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
41, 42, and 43, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
45, 46, and 47, respectively;
(h) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
41, 42, and 43, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
49, 50, and 51, respectively;
(i) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
53, 54, and 55, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
57, 58, and 59, respectively;
(j) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
61, 62, and 63, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
65, 66, and 67, respectively;
(k) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
69, 70, and 71, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
73, 74, and 75, respectively;
(l) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
69, 70, and 71, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
77, 78, and 79, respectively;
(m) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
81, 82, and 83, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
85, 86, and 87, respectively;
or
(n) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
89, 90, and 91, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
93, 94, and 95, respectively.

40 more elements

An isolated cell comprising a nucleic acid encoding the heavy chain of an antibody which binds to human CD73 and a nucleic acid encoding the light chain of the antibody, wherein the heavy and light chains respectively comprise:

(a) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
5, 6, and 7, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
9, 10, and 11, respectively;
(b) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
5, 6, and 7, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
13, 14, and 15, respectively;
(c) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
21, 22, and 23, respectively;
(d) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
25, 26, and 27, respectively;
(e) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
17, 18, and 19, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
29, 30, and 31, respectively;
(f) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
33, 34, and 35, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
37, 38, and 39, respectively;
(g) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
41, 42, and 43, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
45, 46, and 47, respectively;
(h) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
41, 42, and 43, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
49, 50, and 51, respectively;
(i) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
53, 54, and 55, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
57, 58, and 59, respectively;
(j) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
61, 62, and 63, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
65, 66, and 67, respectively;
(k) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
69, 70, and 71, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
73, 74, and 75, respectively;
(l) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
69, 70, and 71, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
77, 78, and 79, respectively;
(m) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
81, 82, and 83, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
85, 86, and 87, respectively;
or
(n) heavy chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
89, 90, and 91, respectively, and light chain CDR1, CDR2, and CDR3 sequences comprising SEQ ID NOs:
93, 94, and 95, respectively.

40 more elements

Dependencies are inferred from the claim text.

Facts

Application

15/432,180Filed 14 Feb 2017

Priority

21 Nov 2014

Published

7 Sep 2017

Term ends

Not estimatedThe source records don’t support an estimate.

Classification47 codes

C07K 16/40
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: against enzymes
A61K 39/3955
Against materials from animals: against proteinaceous materials, e.g. enzymes, hormones, lymphokines
A61K 39/39558
Against materials from animals: against tumor tissues, cells, antigens
A61K 45/06
Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00: mixtures of active ingredients without…

Family

Application62/083,056Us provisional application · filed 21 Nov 2014

Application14/994,828Division · filed 13 Jan 2016

Application15/432,180Division

Application14/994,828Continuation

US 10,167,343 B2Related patent

US 2016/0145350 A1Published application

US 9,605,080 B2Related patent

US 2017/0253665 A1This patent

From the US filing history. Foreign family members aren’t listed.