Granted Patent B2

US 12,649,791 · App. 18/400,974 · Granted Jun 9, 2026

Inventors: Ramesh Baliga (Redwood City, CA); Bruce Keyt (Hillsborough, CA); Dean Ng (San Francisco, CA)

Assignee: IGM BIOSCIENCES, INC.

C07K16/2809G01N33/6854A61K2039/505C07K2317/21C07K2317/35C07K2317/52C07K2317/56C07K2317/622C07K2317/624C07K2317/94C07K2319/31

Abstract

Claims (34)

1 . A polynucleotide encoding an IgM antibody with enhanced serum half-life comprising:

a nucleic acid encoding an IgM heavy chain that comprises an IgM heavy chain constant region fused to a single chain Fv (scFv), a single domain variable region (VHH), or a heavy chain variable region (VH),

a nucleic acid encoding an antibody light chain that comprises a human antibody light chain constant region fused to a light chain variable region (VL), and

a nucleic acid encoding a variant J chain that comprises the amino acid sequence of SEQ ID NO: 2 except for:

an alanine (A), serine(S), or arginine (R) substitution at amino acid Y102 of SEQ ID NO: 2, an alanine (A) substitution at amino acid T103 of SEQ ID NO: 2, an alanine (A) substitution at amino acid N49 of SEQ ID NO: 2, or a combination thereof;

wherein the IgM antibody encoded by the polynucleotide exhibits an increased serum half-life upon administration to a subject animal relative to a reference IgM antibody that is identical except that the J chain comprises SEQ ID NO: 2, and wherein the IgM antibody and the reference IgM antibody are administered in the same way to the same animal species.

2 . The polynucleotide of claim 1 , wherein the IgM heavy chain constant region is a human IgM constant region comprising the amino acid sequence SEQ ID NO: 12.

3 . The polynucleotide of claim 1 , wherein the IgM heavy chain constant region is a variant human IgM constant region that is identical to a human IgM heavy chain constant region except for: an alanine (A) substitution at a position corresponding to amino acid S401 of SEQ ID NO: 12, an alanine (A) substitution at a position corresponding to amino acid E402 of SEQ ID NO: 12, or alanine (A) substitutions at positions corresponding to amino acids S401 and E402 of SEQ ID NO: 12.

4 . The polynucleotide of claim 3 , wherein the IgM heavy chain constant region comprises the amino acid sequence SEQ ID NO: 13 or SEQ ID NO: 14.

5 . The polynucleotide of claim 1 , wherein the variant J chain comprises the amino acid sequence of SEQ ID NO: 2 except for an alanine (A) substitution at amino acid Y102 of SEQ ID NO: 2.

6 . The polynucleotide of claim 5 , wherein the variant J chain comprises the amino acid sequence SEQ ID NO: 3.

7 . The polynucleotide of claim 1 , wherein the variant J chain comprises the amino acid sequence of SEQ ID NO: 2 except for a serine(S) substitution at amino acid Y102 of SEQ ID NO: 2.

8 . The polynucleotide of claim 7 , wherein the variant J chain comprises the amino acid sequence SEQ ID NO: 4.

9 . The polynucleotide of claim 1 , wherein the variant J chain comprises the amino acid sequence of SEQ ID NO: 2 except for an arginine (R) substitution at amino acid Y102 of SEQ ID NO: 2.

10 . The polynucleotide of claim 9 , wherein the variant J chain comprises the amino acid sequence SEQ ID NO: 5.

11 . The polynucleotide of claim 1 , wherein the variant J chain comprises the amino acid sequence of SEQ ID NO: 2 except for an alanine (A) substitution at amino acid T103 of SEQ ID NO: 2.

12 . The polynucleotide of claim 11 , wherein the variant J chain comprises the amino acid sequence SEQ ID NO: 6.

13 . The polynucleotide of claim 1 , wherein the variant J chain further comprises a heterologous polypeptide fused thereto.

14 . An expression vector comprising the polynucleotide of claim 1 .

15 . A host cell comprising the polynucleotide of claim 1 .

16 . A method of producing an IgM antibody with enhanced serum half-life, comprising culturing the host cell of claim 15 , and recovering the IgM antibody.

17 . A polynucleotide encoding an IgM antibody with enhanced serum half-life comprising:

a nucleic acid encoding a variant IgM heavy chain that comprises an IgM heavy chain constant region fused to a single chain Fv (scFv), a single domain variable region (VHH), or a heavy chain variable region (VH), wherein the variant IgM heavy chain constant region is identical to a human IgM heavy chain constant region except for: an alanine (A) substitution at a position corresponding to amino acid S401 of SEQ ID NO: 12, an alanine (A) substitution at a position corresponding to amino acid E402 of SEQ ID NO: 12, or alanine (A) substitutions at positions corresponding to amino acids S401 and E402 of SEQ ID NO: 12; and

a nucleic acid encoding an antibody light chain comprising a human antibody light chain constant region fused to a light chain variable region (VL);

wherein the IgM antibody encoded by the polynucleotide exhibits an increased serum half-life upon administration to a subject animal relative to a reference IgM antibody that is identical except that the IgM heavy chain constant region comprises SEQ ID NO: 12, and wherein the IgM antibody and the reference IgM antibody are administered in the same way to the same animal species.

18 . The polynucleotide of claim 17 , further comprising a nucleic acid encoding a J chain that comprises the amino acid sequence of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 10, SEQ ID NO: 23, or SEQ ID NO: 24.

19 . The polynucleotide of claim 17 , wherein the variant IgM heavy chain constant regions comprise an alanine (A) substitution at the position corresponding to amino acid S401 of SEQ ID NO: 12.

20 . The polynucleotide of claim 19 , wherein the variant IgM heavy chain constant region comprises the amino acid sequence SEQ ID NO: 13.

21 . The polynucleotide of claim 17 , wherein the variant IgM heavy chain constant regions comprise an alanine (A) substitution at the position corresponding to E402 of SEQ ID NO: 12.

22 . The polynucleotide of claim 21 , wherein the variant IgM heavy chain constant region comprises the amino acid sequence SEQ ID NO: 14.

23 . The polynucleotide of claim 17 , wherein the J chain further comprises a heterologous polypeptide fused thereto.

24 . An expression vector comprising the polynucleotide of claim 17 .

25 . A host cell comprising the polynucleotide of claim 17 .

26 . A method of producing an IgM antibody with enhanced serum half-life, comprising culturing the host cell of claim 25 , and recovering the IgM antibody.

Assignments (1)

Continuity (5)

References Cited (183)