IP Library Granted Patent US 9,688,728
Granted Patent B2
US 9,688,728 · App. 14/432,861 · Granted Jun 27, 2017

Bacteriophage gene 3 protein compositions and use as amyloid binding agents

Inventors: Rajaraman Krishnan (Quincy, MA); Richard Fisher (Cambridge, MA)
Assignee: PROCLARA BIOSCIENCES, INC.
C07K14/005A61K38/162A61K48/00C07K14/01C07K2319/00C07K2319/30C12N2750/00022C12N2750/00033
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Quick Facts
Patent No.
US 9,688,728
App. No.
14/432,861
Granted
Jun 27, 2017
Kind
B2
Abstract

The invention relates to agents and to pharmaceutical compositions for reducing the formation of amyloid and/or for promoting the disaggregation of amyloid proteins. The compositions may also be used to detect amyloid.

Claims (39)

1. A fusion protein comprising an amyloid binding fragment of g3p and an Fc fragment of an immunoglobulin, wherein the protein comprises:

(a) amino acids 21-506 of SEQ ID NO:9;

(b) amino acids 22-506 of SEQ ID NO:9;

(c) amino acids 23-506 of SEQ ID NO:9;

(d) amino acids 21-505 of SEQ ID NO:9;

(e) amino acids 22-505 of SEQ ID NO:9;

(f) amino acids 23-505 of SEQ ID NO:9;

(g) amino acids 21-506 of SEQ ID NO:11;

(h) amino acids 22-506 of SEQ ID NO:11;

(i) amino acids 23-506 of SEQ ID NO:11;

(j) amino acids 21-505 of SEQ ID NO:11;

(k) amino acids 22-505 of SEQ ID NO:11;

(l) amino acids 23-505 of SEQ ID NO:11;

(m) amino acids 21-509 of SEQ ID NO:13;

(n) amino acids 22-509 of SEQ ID NO:13;

(o) amino acids 23-509 of SEQ ID NO:13;

(p) amino acids 21-508 of SEQ ID NO:13;

(q) amino acids 22-508 of SEQ ID NO:13;

(r) amino acids 23-508 of SEQ ID NO:13;

(s) amino acids 21-528 of SEQ ID NO:31;

(t) amino acids 22-528 of SEQ ID NO:31;

(u) amino acids 23-528 of SEQ ID NO:31;

(v) amino acids 21-527 of SEQ ID NO:31;

(w) amino acids 22-527 of SEQ ID NO:31;

(x) amino acids 23-527 of SEQ ID NO:31; or

(y) a mutant or variant that is at least 95% identical to the amino acid sequence of any one of (a)-(x) and is capable of binding to amyloid.

2. The fusion protein of claim 1 , wherein the amyloid binding fragment of g3p in any one of (a)-(x) has up to 5 amino acid substitutions.

3. The fusion protein of claim 1 , wherein the fusion protein comprises amino acids 21-509 of SEQ ID NO:13, or a mutant or variant that comprises up to 5 amino acid substitutions as compared to the corresponding g3p portion of SEQ ID NO:13.

4. The fusion protein of claim 1 , wherein the fusion protein comprises amino acids 22-509 of SEQ ID NO:13, or a mutant or variant that comprises up to 5 amino acid substitutions as compared to the corresponding g3p portion of SEQ ID NO:13.

5. The fusion protein of claim 1 , wherein the fusion protein comprises amino acids 23-509 of SEQ ID NO:13, or a mutant or variant that comprises up to 5 amino acid substitutions as compared to the corresponding g3p portion of SEQ ID NO:13.

6. The fusion protein of claim 1 , wherein the fusion protein comprises amino acids 21-508 of SEQ ID NO:13, or a mutant or variant that comprises up to 5 amino acid substitutions as compared to the corresponding g3p portion of SEQ ID NO:13.

7. The fusion protein of claim 1 , wherein the fusion protein comprises amino acids 22-508 of SEQ ID NO:13, or a mutant or variant that comprises up to 5 amino acid substitutions as compared to the corresponding g3p portion of SEQ ID NO:13.

8. The fusion protein of claim 1 , wherein the fusion protein comprises amino acids 23-508 of SEQ ID NO:13, or a mutant or variant that comprises up to 5 amino acid substitutions as compared to the corresponding g3p portion of SEQ ID NO:13.

9. The fusion protein of claim 1 , wherein the fusion protein is less immunogenic in humans than SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13 or SEQ ID NO:31.

10. A pharmaceutical composition comprising a therapeutically effective amount of the fusion protein of claim 1 , and a pharmaceutically acceptable carrier.

11. A method of treating a patient for a disease or condition associated with misfolded and/or aggregated amyloid beta, tau, α-synuclein, and/or prion protein, comprising administering to the patient the fusion protein of claim 1 , to reduce amyloid, inhibit amyloid formation, inhibit amyloid aggregation, or remove and/or prevent the formation of toxic oligomers.

12. A method of treating a patient for a disease or condition by administering to the patient the fusion protein of claim 1 , wherein the disease or condition is selected from the group consisting of Alzheimer's disease, early onset Alzheimer's disease, late onset Alzheimer's disease, presymptomatic Alzheimer's disease, Parkinson's disease, and bovine spongiform encephalitis (BSE.

13. The method of claim 12 , wherein the patient is positive for the biomarker florbetapir when that biomarker is used as an imaging agent in positron emission tomography.

14. The method of claim 12 , wherein the disease or condition is Parkinson's disease or Alzheimer's disease.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 3, 2023
From: PROCLARA BIOSCIENCES INC.
To: AMYL THERAPEUTICS SRL
Reel/Frame 062952/0788 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 8, 2016
From: KRISHNAN, RAJARAMAN
To: NEUROPHAGE PHARMACEUTICALS, INC.
Reel/Frame 039676/0232 →
CHANGE OF NAME Recorded Aug 1, 2016
From: NEUROPHAGE PHARMACEUTICALS, INC.
To: PROCLARA BIOSCIENCES, INC.
Reel/Frame 039535/0182 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 22, 2015
From: FISHER, RICHARD
To: NEUROPHAGE PHARMACEUTICALS, INC.
Reel/Frame 035877/0182 →
Continuity (5)
Provisional Application 61708709 · Oct 2, 2012
Provisional Application 61730316 · Nov 27, 2012
Provisional Application 61801349 · Mar 15, 2013
Provisional Application 61828105 · May 28, 2013
Related Publication 20150376239A1 · Dec 31, 2015