Granted Patent B2

US 12,509,503 · App. 17/615,309 · Granted Dec 30, 2025

Inventors: Ali Ellebedy (St. Louis, MO); Florian Krammer (New York, NY); Ian Wilson (La Jolla, CA)

Assignees: Washington University; The Scripps Research Institute; Icahn School of Medicine at Mt. Sinai

C07K16/1018C07K16/40C07K2317/34C07K2317/52C07K2317/55C07K2317/565C07K2317/76

Abstract

Claims (33)

1 . An antibody or antigen-binding fragment, wherein the antibody or antigen-binding fragment comprises:

(a) a heavy chain variable region comprising a CDR-H1 comprising the amino acid sequence of GFKFDDYAM (SEQ ID NO:13); a CDR-H2 comprising the amino acid sequence of LNWNGDITA (SEQ ID NO:7); and a CDR-H3 comprising the amino acid sequence of SWGDYTRGPEPKITWY (SEQ ID NO:14), and

a light chain variable region comprising a CDR-L1 comprising the amino acid sequence of GIDGYL (SEQ ID NO:15); a CDR-L2 comprising the amino acid sequence of SLL; and a CDR-L3 comprising the amino acid sequence of LDSYPLFTF (SEQ ID NO:16);

(b) a heavy chain variable region comprising a CDR-H1 comprising the amino acid sequence of GFTFDDYGM (SEQ ID NO: 1); a CDR-H2 comprising the amino acid sequence of LNWNGDITA (SEQ ID NO:7); and a CDR-H3 comprising the amino acid sequence of TWGEYTTREEPIHSWY (SEQ ID NO:3), and

a light chain variable region comprising a CDR-L1 comprising the amino acid sequence of DISSFL (SEQ ID NO:8); a CDR-L2 comprising the amino acid sequence of SLL; and

a CDR-L3 comprising the amino acid sequence of LNSYPLFTF (SEQ ID NO:6); or

(c) a heavy chain variable region comprising a CDR-H1 comprising the amino acid sequence of GFTFDDYGM (SEQ ID NO: 1); a CDR-H2 comprising the amino acid sequence of LNWNGDITA (SEQ ID NO:7); and a CDR-H3 comprising the amino acid sequence of TWGDYTTGEEIINSWY (SEQ ID NO:10), and

a light chain variable region comprising a CDR-L1 comprising the amino acid sequence of DISSYL (SEQ ID NO:11); a CDR-L2 comprising the amino acid sequence of SLL; and a CDR-L3 comprising the amino acid sequence of LKSYPLFTF (SEQ ID NO:12).

2 . The antibody or antigen-binding fragment of claim 1 , wherein

the heavy chain variable region comprises a CDR-H1 comprising the amino acid sequence of GFKFDDYAM (SEQ ID NO:13) a CDR-H2 comprising the amino acid sequence of LNWNGDITA (SEQ ID NO:7); and a CDR-H3 comprising the amino acid sequence of SWGDYTRGPEPKITWY (SEQ ID NO:14), and

the light chain variable region comprises a CDR-L1 comprising the amino acid sequence of GIDGYL (SEQ ID NO:15): a CDR-L2 comprising the amino acid sequence of SLL; and a CDR-L3 comprising the amino acid sequence of LDSYPLFTF (SEQ ID NO:16).

3 . The antibody or antigen-binding fragment of claim 2 , wherein the heavy chain variable region comprises the amino acid sequence of EVQLVESGGRALRPGGSLRLSCAASGFKFDDYAMSWVRQVPGKGLEFVSGLNWNGDIT AYTDSVKGRFTVSRDNAKNSLYLHINSPKPEDTALYYCARTSSWGDYTRGPEPKITWYF DLWGRGTLVTVSS (SEQ ID NO:44), and the light chain variable region comprises the amino acid sequence of DIQLTQSPSFLSASVGDRITITCRASQGIDGYLAWYQQRPGKAPNLLIYAASLLQSGVPSR FSGSGYGTEFTLTISSLQPEDFATYYCQHLDSYPLFTFGPGTKVDIK (SEQ ID NO:45).

4 . The antibody or antigen-binding fragment of claim 1 , wherein

the heavy chain variable region comprises a CDR-H1 comprising the amino acid sequence of GFTFDDYGM (SEQ ID NO:1): a CDR-H2 comprising the amino acid sequence of LNWNGDITA (SEQ ID NO:7); and a CDR-H3 comprising the amino acid sequence of TWGEYTTREEPIHSWY (SEQ ID NO:3), and

the light chain variable region comprises a CDR-L1 comprising the amino acid sequence of DISSFL (SEQ ID NO:8): a CDR-L2 comprising the amino acid sequence of SLL; and a CDR-L3 comprising the amino acid sequence of LNSYPLFTF (SEQ ID NO:6).

5 . The antibody or antigen-binding fragment of claim 4 , wherein the heavy chain variable region comprises the amino acid sequence of EVQLVESGGRVVRPGGSLRLSCAASGFTFDDYGMSWVRQAPGKGLEFVSGLNWNGDIT AFTDSVKGRFTISRDNAKSSLYLQMNSLRADDTAFYYCARVRTWGEYTTREEPIHSWYF DLWGRGTLVTVSS (SEQ ID NO:40), and the light chain variable region comprises the amino acid sequence of DIQLTQSPSFLSASVGDRVTITCRASQDISSFLAWYQQKPGNAPKVLIYAASLLQSGVPSR FSGSGSGTDFTLTISSLQPEDFATYYCQQLNSYPLFTFGPGTKVDIK (SEQ ID NO:41).

6 . The antibody or antigen binding fragment of claim 1 , wherein

heavy chain variable region comprises a CDR-H1 comprising the amino acid sequence of GFTFDDYGM (SEQ ID NO:1): a CDR-H2 comprising the amino acid sequence of LNWNGDITA (SEQ ID NO:7); and a CDR-H3 comprising the amino acid sequence of TWGDYTTGEEIINSWY (SEQ ID NO:110), and

the light chain variable region comprises a CDR-L1 comprising the amino acid sequence of DISSYL (SEQ ID NO:11): a CDR-L2 comprising the amino acid sequence of SLL; and a CDR-L3 comprising the amino acid sequence of LKSYPLFTF (SEQ ID NO:12).

7 . The antibody or antigen binding fragment of claim 6 , wherein the heavy chain variable region comprises the amino acid sequence of EVQLVESGGRVVRPGGSLRLSCAASGFTFDDYGMSWVRQPPGKGLEFVSGLNWNGDIT AFTDSVKGRFTISRDNVKSSLYLQMNSLRADDTAFYYCARVRTWGDYTTGEEIINSWYF DLWGRGTLVTVSS (SEQ ID NO:42), and the light chain variable region comprises the amino acid sequence of DIQLTQSPSFLSASVGDRVTITCRASQDISSYLAWYQQKPGNAPKLLIYAASLLQSGVPSR FSAFGSGTEFTLTISSLQPEDFATYYCQHLKSYPLFTFGPGTKVDIK (SEQ ID NO:43).

8 . The antibody or antigen-binding fragment of claim 2 , comprising a heavy chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO:44, and a light chain variable region comprising an amino acid sequence having at least 90% identity to SEQ ID NO:45.

9 . The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment binds an influenza virus.

10 . The antibody or antigen-binding fragment of claim 9 , wherein the antibody or antigen-binding fragment specifically binds to a neuraminidase.

11 . The antibody or antigen-binding fragment of claim 10 , wherein the antibody or antigen-binding fragment inhibits the neuraminidase with an IC50 of about 0.0001 μg/ml to about 30 μg/ml.

12 . The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment is humanized.

13 . The antibody or antigen binding fragment of claim 1 , wherein the antibody or antigen binding fragment is a monoclonal antibody and/or is an IgG antibody.

14 . The antibody or antigen bind fragment of claim 1 , wherein the antibody or antigen bind fragment comprises a hinge region or Fc region that contains at least one amino acid substitution, deletion, or insertion relative to the sequence of a wild-type hinge region or a wild-type Fc region, and wherein the substitution, deletion, or insertion prevents or reduces recycling of the antibody or antigen-binding fragment.

15 . A nucleic acid comprising a nucleotide sequence encoding the heavy chain variable region and/or the light chain variable region of the antibody or antigen-binding fragment of claim 1 .

16 . An expression vector comprising the nucleic acid of claim 15 .

17 . A host cell comprising the expression vector of claim 16 .

18 . A vaccine comprising an antibody or antigen-binding fragment of claim 1 .

19 . A pharmaceutical composition, comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier or excipient.

20 . The nucleic acid of claim 15 , comprising the nucleotide sequence of SEQ ID NO:47 and/or the nucleotide sequence of SEQ ID NO:51.

Assignments (3)

Continuity (2)

References Cited (22)