IP Library › Granted Patent US 11,725,059

Granted Patent B2

US 11,725,059 · App. 17/173,716 · Granted Aug 15, 2023

Antibodies targeting B-cell maturation antigen and methods of use

Inventors: Renier J. Brentjens (New York, NY); Eric L. Smith (New York, NY); Cheng Liu (Emeryville, CA)

Assignees: MEMORIAL SLOAN KETTERING CANCER CENTER; EUREKA THERAPEUTICS, INC.

C07K16/2878 A61K47/6849 A61P35/00 C07K14/70575 C07K16/2896 G01N33/6863 C07K2317/21 C07K2317/24 C07K2317/34 C07K2317/622 C07K2317/92 C07K2319/21 C07K2319/30 C07K2319/42 G01N2333/70578

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Quick Facts

Patent No.: US 11,725,059
App. No.: 17/173,716
Filed: Feb 11, 2021
Granted: Aug 15, 2023
Kind: B2
Examiner: NATARAJAN, MEERA
Art Unit: 1643
USPC: 424/136.1

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The presently disclosed subject matter provides antibodies that bind to B-cell maturation antigen (BCMA) and methods of using the same.

Claims (346)

1. A method of treating a tumor associated with B-cell maturation antigen (BCMA) in a subject, comprising administering to the subject an effective amount of an anti-BCMA single-chain variable fragment (scFv) comprising a heavy chain variable region and a light chain variable region, wherein:

(a) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 53, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 54;

(b) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 65, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 66;

(c) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 21, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 22;

(d) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 1, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 2;

(e) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 5, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 6;

(f) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 9, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 10;

(g) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 13, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 14;

(h) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 17, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 18;

(i) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 25, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 26;

(j) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 29, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 30;

(k) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 33, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 34;

(l) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 37, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 38;

(m) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 41, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 42;

(n) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 45, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 46;

(o) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 49, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 50;

(p) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 57, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 58; or

(q) the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 61, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 62.

2. The method of claim 1 , wherein:

(a) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 53, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 54;

(b) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 65, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 66;

(c) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 21, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 22;

(d) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 1, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 2;

(e) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 5, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 6;

(f) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 9, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 10;

(g) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 13, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 14;

(h) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 17, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 18;

(i) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 25, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 26;

(j) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 29, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 30;

(k) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 33, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 34;

(l) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 37, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 38;

(m) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 41, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 42;

(n) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 45, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 46;

(o) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 49, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 50;

(p) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 57, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 58; or

(q) the heavy chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 61, and the light chain variable region comprises an amino acid sequence that has at least about 90% sequence identity to the amino acid sequence set forth in SEQ ID NO: 62.

3. The method of claim 1 , wherein:

(a) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 53, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 54;

(b) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 65, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 66;

(c) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 21, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 22;

(d) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 1, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 2;

(e) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 5, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 6;

(f) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 9, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 10;

(g) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 13, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 14;

(h) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 17, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 18;

(i) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 25, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 26;

(j) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 29, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 30;

(k) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 33, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 34;

(l) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 37, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 38;

(m) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 41, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 42;

(n) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 45, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 46;

(o) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 49, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 50;

(p) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 57, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 58; or

(q) the heavy chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 61, and the light chain variable region comprises the amino acid sequence set forth in SEQ ID NO: 62.

4. The method of claim 1 , wherein the scFv comprises the amino acid sequence set forth in SEQ ID NO: 85, SEQ ID NO: 88, SEQ ID NO: 77, SEQ ID NO: 72, SEQ ID NO: 73, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 78, SEQ ID NO: 79, SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 86, or SEQ ID NO: 87.

5. The method of claim 1 , wherein the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 53, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 54.

6. The method of claim 1 , wherein the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 65, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 66.

7. The method of claim 1 , wherein the heavy chain variable region comprises the CDR1, CDR2, and CDR3 of the heavy chain variable sequence set forth in SEQ ID NO: 21, and the light chain variable region comprises the CDR1, CDR2, and CDR3 of the light chain variable region sequence set forth in SEQ ID NO: 22.

8. The method of claim 1 , wherein the method reduces the number of tumor cells, reduces the tumor size, or eradicates the tumor in the subject.

9. The method of claim 1 , wherein the tumor is selected from the group consisting of multiple myeloma, Non-Hodgkin Lymphoma, Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, glioblastoma, and Waldenstrom's Macroglobulinemia.

10. The method of claim 1 , wherein the tumor is multiple myeloma.

11. The method of claim 1 , wherein the subject is a human.

12. A method of treating a tumor associated with B-cell maturation antigen (BCMA) in a subject, comprising administering to the subject an effective amount of an anti-BCMA single-chain variable fragment (scFv) comprising a heavy chain variable region and a light chain variable region, wherein:

(a) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 167, 168, and 169, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 170, 171, and 172, respectively;

(b) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 185, 186, and 187, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 188, 189, and 190, respectively;

(c) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 119, 120, and 121, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 122, 123, and 124, respectively;

(d) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 89, 90, and 91, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 92, 93, and 94, respectively;

(e) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 95, 96, and 97, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 98, 99, and 100, respectively;

(f) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 101, 102, and 103, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 104, 105, and 106, respectively;

(g) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 107, 108, and 109, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 110, 111, and 112, respectively;

(h) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 113, 114, and 115, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 116, 117, and 118, respectively;

(i) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 125, 126, and 127, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 128, 129, and 130, respectively;

(j) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 131, 132, and 133, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 134, 135, and 136, respectively;

(k) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 137, 138, and 139, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 140, 141, and 142, respectively;

(l) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 143, 144, and 145, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 146, 147, and 149, respectively;

(m) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 149, 150, and 151, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 152, 152, and 154, respectively;

(n) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 155, 156, and 157, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 158, 159, and 160, respectively;

(o) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 161, 162, and 163, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 164, 165, and 166, respectively;

(p) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 173, 174, and 175, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 176, 177, and 178, respectively; or

(q) the heavy chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 179, 180, and 181, respectively; and the light chain variable region comprises a CDR1, a CDR2, and a CDR3 sequence set forth in SEQ ID NOS: 182, 183, and 184, respectively.

13. The method of claim 12 , wherein:

14. The method of claim 12 , wherein: