Granted Patent B2

US 12,331,125 · App. 18/510,256 · Granted Jun 17, 2025

Inventors: Brian P. Fiske (Waltham, MA); Nimish Gera (Waltham, MA); Alexander J. Nichols (Lincoln, MA)

Assignee: Mythic Therapeutics, Inc.

C07K16/2863A61K47/68031A61K47/68035A61K47/6849A61P35/00C07K16/32A61K38/00A61K2039/505C07K2317/52C07K2317/73C07K2317/77C07K2317/94

Abstract

Claims (42)

1. An antibody-drug conjugate, wherein the antibody-drug conjugate comprises:

(a) a heavy chain variable domain and a light chain variable domain selected from the group of:

(i) SEQ ID NO: 5 and SEQ ID NO: 6, respectively;

(ii) SEQ ID NO: 11 and SEQ ID NO: 12, respectively;

(iii) SEQ ID NO: 13 and SEQ ID NO: 14, respectively;

(iv) SEQ ID NO: 15 and SEQ ID NO: 16, respectively;

(v) SEQ ID NO: 17 and SEQ ID NO: 18, respectively; and

(vi) SEQ ID NO: 21 and SEQ ID NO: 22, respectively;

(b) a light chain constant region sequence of SEQ ID NO: 157 comprising a valine to cysteine substitution at amino acid position 98, wherein the drug is monomethyl auristatin E (MMAE) and the MMAE is conjugated to the cysteine at amino acid position 98 via a valine-citrulline (vc) linker; and

(c) a heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 155 or SEQ ID NO: 189 optionally comprising one or more of (A) through (C):

(A) a lysine to cysteine substitution at amino acid position 105 and deletion of a threonine at amino acid positions 106 and 108;

(B) a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139; and

(C) a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317.

2. The antibody-drug conjugate of claim 1 , comprising a heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 155 or SEQ ID NO: 189 further comprising a lysine to cysteine substitution at amino acid position 105 and deletion of a threonine at amino acid positions 106 and 108.

3. The antibody-drug conjugate of claim 2 , comprising heavy chain and light chain sequences selected from the group of:

(i) SEQ ID NO: 35 and SEQ ID NO: 42, respectively;

(ii) SEQ ID NO: 59 and SEQ ID NO: 66, respectively;

(iii) SEQ ID NO: 67 and SEQ ID NO: 74, respectively;

(iv) SEQ ID NO: 75 and SEQ ID NO: 82, respectively;

(v) SEQ ID NO: 83 and SEQ ID NO: 90, respectively; and

(vi) SEQ ID NO: 99 and SEQ ID NO: 106, respectively.

4. The antibody-drug conjugate of claim 3 , wherein the heavy and light chain sequences comprise SEQ ID NO: 75 and SEQ ID NO: 82, respectively.

5. The antibody-drug conjugate of claim 1 , comprising a heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 155 or SEQ ID NO: 189 comprising a lysine to cysteine substitution at amino acid position 105 and deletion of a threonine at amino acid positions 106 and 108; and a methionine to leucine substitution at amino acid position 311 and an asparagine to serine substitution at amino acid position 317.

6. The antibody-drug conjugate of claim 5 , wherein the antibody comprises heavy chain and light chain sequences selected from the group of:

(i) SEQ ID NO: 36 and SEQ ID NO: 42, respectively;

(ii) SEQ ID NO: 60 and SEQ ID NO: 66, respectively;

(iii) SEQ ID NO: 68 and SEQ ID NO: 74, respectively;

(iv) SEQ ID NO: 76 and SEQ ID NO: 82, respectively;

(v) SEQ ID NO: 84 and SEQ ID NO: 90, respectively; and

(vi) SEQ ID NO: 100 and SEQ ID NO: 106, respectively.

7. The antibody-drug conjugate of claim 1 , wherein the heavy chain CH1-CH2-CH3 sequence of SEQ ID NO: 155 or SEQ ID NO: 189 comprises:

a lysine to cysteine substitution at amino acid position 105 and deletion of a threonine at amino acid positions 106 and 108; and

a methionine to tyrosine substitution at amino acid position 135, a serine to threonine substitution at amino acid position 137, and a threonine to glutamic acid substitution at amino acid position 139.

8. The antibody-drug conjugate of claim 7 , wherein the antibody comprises heavy chain and light chain sequences selected from the group of:

(i) SEQ ID NO: 37 and SEQ ID NO: 42, respectively;

(ii) SEQ ID NO: 61 and SEQ ID NO: 66, respectively;

(iii) SEQ ID NO: 69 and SEQ ID NO: 74, respectively;

(iv) SEQ ID NO: 77 and SEQ ID NO: 82, respectively;

(v) SEQ ID NO: 85 and SEQ ID NO: 90, respectively; and

(vi) SEQ ID NO: 101 and SEQ ID NO: 106, respectively.

9. A pharmaceutical composition comprising an effective amount of the antibody-drug conjugate of claim 1 .

10. A method of treating cancer, reducing the volume of a tumor, or inducing cell death in a cancer cell, wherein the cancer or tumor is characterized by having a population of cancer cells that have cMet presented on their surface, comprising administering an effective amount of the antibody-drug conjugate of claim 1 to the subject.

Assignments (3)

Continuity (3)

References Cited (162)