Granted Patent B2

US 12,491,259 · App. 18/726,319 · Granted Dec 9, 2025

Inventors: Cynthia Bamdad (Boston, MA); Benoit Smagghe (Honolulu, HI); Scott Moe (Sudbury, MA); Thomas Jeon (Woburn, MA)

Assignee: MINERVA BIOTECHNOLOGIES CORPORATION

A61K47/6851A61K47/65A61K47/68031C07K16/3092C07K2317/565

Abstract

Claims (54)

1 . A conjugate of Formula (I):

[Ab]-[Z-L-R-X] y   Formula (I),

wherein:

[Ab] is an antibody comprising an anti-MUC1* binding domain comprising

three heavy chain (HC) complementarity determining regions (CDRs): MUC1* HC-CDR1, MUC1* HC-CDR2, and MUC1* HC-CDR3; and

three light chain (LC) complementarity determining regions (CDRs): MUC1* LC-CDR1, MUC1* LC-CDR2, and MUC1* LC-CDR3;

wherein:

(a) the MUC1* HC-CDR1 comprises the amino acid sequence of SEQ ID NO: 1, the MUC1* HC-CDR2 comprises the amino acid sequence of SEQ ID NO: 2, the MUC1* HC-CDR3 comprises the amino acid sequence of SEQ ID NO: 3, the MUC1* LC-CDR1 comprises the amino acid sequence of SEQ ID NO: 13, the MUC1* LC-CDR2 comprises the amino acid sequence of SEQ ID NO: 14, and the MUC1* LC-CDR3 comprises the amino acid sequence of SEQ ID NO: 15; or

(b) the MUC1* HC-CDR1 comprises the amino acid sequence of SEQ ID NO: 4, the MUC1* HC-CDR2 comprises the amino acid sequence of SEQ ID NO: 5, the MUC1* HC-CDR3 comprises the amino acid sequence of SEQ ID NO: 6, the MUC1* LC-CDR1 comprises the amino acid sequence of SEQ ID NO: 16, the MUC1* LC-CDR2 comprises the amino acid sequence of SEQ ID NO: 17, and the MUC1* LC-CDR3 comprises the amino acid sequence of SEQ ID NO: 18;

Z is a conjugation moiety that forms a covalent bond with a sulfur atom of a cysteine residue of the antibody;

L is a di- or tri- or tetra-peptide linking moiety, wherein Z is bonded to the N-terminus of L and R is bonded to the C-terminus of L;

R is a coupling moiety;

X is selected from exatecan, Dxd, monomethyl auristatin E (MMAE), and monomethyl auristatin F (MMAF), wherein Dxd is —O—CH2CO-Exatecan;

and

y is an integer from 1 to 8.

2 . The conjugate of claim 1 , wherein the antibody comprises:

a. a heavy chain comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 39, and

a light chain comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 42; or

b. a heavy chain comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 45, and

a light chain comprising a sequence having at least 90% identity to the amino acid sequence of SEQ ID NO: 48.

3 . The conjugate of claim 1 , wherein y is at least 3.

4 . The conjugate of claim 1 , wherein L comprises two, three, or four amino acids selected from a group comprising valine, citrulline, glycine, alanine, isoleucine, methionine, tryptophan, serine, threonine, asparagine, glutamine, cysteine, tyrosine, leucine, tryptophan, proline, lysine, arginine, histidine aspartate, glutamate and phenylalanine.

5 . The conjugate of claim 4 , wherein L is

a. a dipeptide linking moiety comprising:

or

b. a tetra-peptide linking moiety comprising:

6 . The conjugate of claim 1 , wherein R comprises:

wherein the * indicates the point of attachment for X.

7 . The conjugate of claim 1 , wherein X is exatecan or Dxd.

8 . The conjugate of claim 1 , wherein X is monomethyl auristatin E (MMAE) or monomethyl auristatin F (MMAF).

9 . The conjugate of claim 1 , comprising:

10 . The conjugate of claim 9 , wherein:

the MUC1* HC-CDR1 comprises the amino acid sequence of SEQ ID NO: 4,

the MUC1* HC-CDR2 comprises the amino acid sequence of SEQ ID NO: 5,

the MUC1* HC-CDR3 comprises the amino acid sequence of SEQ ID NO: 6,

the MUC1* LC-CDR1 comprises the amino acid sequence of SEQ ID NO: 16,

the MUC1* LC-CDR2 comprises the amino acid sequence of SEQ ID NO: 17, and

the MUC1* LC-CDR3 comprises the amino acid sequence of SEQ ID NO: 18.

11 . The conjugate of claim 9 , wherein Ab comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 38 and a light chain consisting of the amino acid sequence of SEQ ID NO: 41.

12 . The conjugate of claim 9 , wherein Ab comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 44 and a light chain consisting of the amino acid sequence of SEQ ID NO: 47.

13 . The conjugate of claim 12 , wherein y is at least 3.

14 . The conjugate of claim 1 , comprising:

wherein Ab comprises a heavy chain consisting of the amino acid sequence of SEQ ID NO: 38 and a light chain consisting of the amino acid sequence of SEQ ID NO: 41.

15 . The conjugate of claim 1 , comprising:

wherein Ab comprises:

a heavy chain consisting of the amino acid sequence of SEQ ID NO: 38 and a light chain consisting of the amino acid sequence of SEQ ID NO: 41, or

a heavy chain consisting of the amino acid sequence of SEQ ID NO: 44 and a light chain consisting of the amino acid sequence of SEQ ID NO: 47.

16 . The conjugate of claim 1 , comprising:

17 . The conjugate of claim 1 , wherein the antibody comprises:

a. a heavy chain comprising the amino acid sequence of SEQ ID NO: 39, and a light chain comprising the amino acid sequence of SEQ ID NO: 42; or

b. a heavy chain comprising the amino acid sequence of SEQ ID NO: 45, and a light chain comprising the amino acid sequence of SEQ ID NO: 48.

18 . A method of treating cancer comprising administering the conjugate of claim 1 to a subject.

19 . The method of claim 18 , wherein the cancer expresses MUC1*.

20 . The method of claim 19 , wherein the cancer comprises breast cancer, colon cancer, prostate cancer, pancreatic cancer, or lung cancer.

Assignments (1)

Continuity (2)

References Cited (250)