US2017260286A1PendingUtilityA1
Antigen-Binding Fusion Proteins with Modified HSP70 Domains
Assignee: MASSACHUSETTS GEN HOSPITALPriority: Mar 10, 2016Filed: Mar 10, 2017Published: Sep 14, 2017
Est. expiryMar 10, 2036(~9.7 yrs left)· nominal 20-yr term from priority
A61P 35/00A61K 38/00C07K 2319/74C07K 2319/30C07K 2319/70C07K 2319/33C07K 14/35A61K 2039/505C07K 2317/622C07K 16/3069C07K 2317/76C07K 16/30C07K 19/00
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Claims
Abstract
The invention relates to fusion proteins comprising an antigen binding domain fused with a modified heat shock 70 protein. The invention further relates to methods of using the fusion proteins to induce an immune response to antigens and to treat diseases associated with antigens.
Claims
exact text as granted — not AI-modified1 . A fusion protein comprising an antigen binding domain fused in frame to a fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) of less than 200 amino acids, wherein the HSP70 fragment comprises a minimal HSP70 sequence.
2 . The fusion protein of claim 1 , wherein the HSP70 fragment consists of the minimal HSP70 sequence.
3 . The fusion protein of claim 1 , wherein the minimal HSP70 sequence is amino acid residues 368-495 of M. tuberculosis HSP70 (SEQ ID NO:1).
4 . The fusion protein of claim 3 , comprising the amino acid sequence of SEQ ID NO:3.
5 . The fusion protein of claim 1 , wherein the HSP70 fragment comprises a modified CD94 domain.
6 . The fusion protein of claim 5 wherein the modified CD94 domain consists of an amino acid sequence selected from:
(SEQ ID NO: 16);
AAHNNLLGSFELTG;
(SEQ ID NO: 17)
AAHNNLLGRFELTG;
(SEQ ID NO: 18)
AAHNNLLGRFELSG;
(SEQ ID NO: 19)
TKENNLLGRFELSG;
or
(SEQ ID NO: 20)
TRDNNLLGRFELSG.
7 . (canceled)
8 . The fusion protein of claim 6 , comprising the amino acid sequence of SEQ ID NO:5.
9 . (canceled)
10 . The fusion protein of claim 6 , comprising an amino acid sequence at least 90% identical to SEQ ID NO:7.
11 . The fusion protein of claim 1 , further comprising the modification V410F (numbering according to SEQ ID NO:1).
12 . The fusion protein of claim 1 , further comprising a linker between the antigen binding domain and the HSP70 fragment.
13 . The fusion protein of claim 12 , wherein said linker comprises an amino acid sequence selected from the group consisting of: GGSSRSS (SEQ ID NO: 21), (GGGSGGG) (SEQ ID NO: 22), GGGGSGGGGSGGGGS (SEQ ID NO: 23), GGSSRSSSSGGGGSGGGG (SEQ ID NO: 24), and GGSSESSSSGGGGSGGGG (SEQ ID NO: 25).
14 . (canceled)
15 . The fusion protein of claim 13 , comprising the amino acid sequence of SEQ ID NO:9.
16 . (canceled)
17 . The fusion protein of claim 13 , comprising the amino acid sequence of SEQ ID NO: 11.
18 . A fusion protein comprising an antigen binding domain fused in frame to a fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) of at least 100 amino acids and comprising no more than amino acids 1-495 of SEQ IP NO:1.
19 - 26 . (canceled)
27 . A fusion protein comprising an antigen binding domain fused in frame to a fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) comprising the amino acid sequence of SEQ ID NO:26.
28 . A fusion protein comprising an antigen binding domain fused in frame to a chimeric Mycobacterium tuberculosis heat shock protein 70 (HSP70), wherein the chimeric HSP70 comprises a backbone of a human HSP70 amino acid sequence wherein a beta sheet domain of-about amino acid residues 367 to 479 (numbering based on SEQ ID NO:29) are substituted with a beta sheet domain of about amino acid residues 395 to 541 of M. tuberculosis HSP70 (numbering based on SEQ ID NO:1).
29 . The fusion protein of claim 1 , wherein the antigen binding domain is an engineered antibody or fragment thereof.
30 . The fusion protein of claim 1 , wherein the antigen binding domain is an scFv.
31 . The fusion protein of claim 1 , wherein the antigen binding domain binds specifically to mesothelin.
32 . The fusion protein of claim 1 , wherein the antigen binding domain is a scFv that binds specifically to mesothelin.
33 . The fusion protein of claim 32 , wherein the scFv comprises the amino acid sequence of SEQ ID NO:30.
34 . The fusion protein of claim 1 , further comprising a leader sequence on the N-terminus.
35 . The fusion protein of claim 34 , wherein the leader sequence is a plant leader sequence.
36 . A pharmaceutical composition comprising an effective amount of the fusion protein of claim 1 and a pharmaceutical acceptable carrier.
37 . An immunogenic composition or vaccine comprising the fusion protein of claim 1 .
38 . A kit comprising the fusion protein of claim 1 and packaging means thereof.
39 . An isolated nucleic acid encoding the fusion protein of claim 1 .
40 - 45 . (canceled)
46 . An expression vector comprising the nucleic acid of claim 39 .
47 . A cell comprising the isolated nucleic acid of claim 39 .
48 - 49 . (canceled)
50 . A method for inducing an immune response to an antigen in a subject, comprising administering to the subject the fusion protein of claim 1 that specifically binds the antigen, thereby inducing an immune response.
51 . A method of treating a disease associated with an antigen in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the fusion protein of claim 1 that specifically binds the antigen, thereby treating the disease.
52 - 57 . (canceled)Cited by (0)
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