IP Library › Granted Patent US 7,429,567

Granted Patent B2

US 7,429,567 · App. 11/320,468 · Granted Sep 30, 2008

Sustained delivery of PDGF using self-assembling peptide nanofibers

Assignee: The Brigham and Women's Hospital, Inc.

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Quick Facts

Patent No.: US 7,429,567
App. No.: 11/320,468
Granted: Sep 30, 2008
Kind: B2

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Abstract

The present invention is directed to a therapeutic composition in which human PDGF is bound directly to peptides that self assemble into a biologically compatible gel. When implanted in a patient's body, the composition provides for the slow, sustained release of PDGF. The composition will be especially useful in treating patients who have undergone a myocardial infarction.

Claims (235)

1. A method of treating a patient who has had a myocardial infarction; wound; damaged ligament, tendon or cartilage; or damaged nerve tissue, comprising: administering to said patient a pharmaceutical composition comprising a biologically compatible peptide membrane, wherein

a) said biologically compatible peptide membrane comprises self-assembling peptides, wherein said self-assembling peptides:

i) are 12-200 amino acids in length;

ii) have alternating hydrophobic and hydrophilic amino acids;

iii) are complementary; and

iv) are structurally compatible;

(b) at least 0.1% of said self-assembling peptides are bound directly to PDGF; and

2. The method of claim 1 wherein said method is a treatment for myocardial infarction.

3. The method of claim 1 wherein said method is a treatment for a wound.

4. The method of claim 1 wherein said method is a treatment for a damaged ligament, tendon or cartilage.

5. The method of claim 1 wherein said method is a treatment for damaged nerve tissue.

6. The method of claim 1 , wherein said biologically compatible peptide membrane consists of self-assembling peptides, wherein:

a) said peptides are 12-24 amino acids in length; and

b) 0.5-10% of said peptides are bound to PDGF.

7. The method of claim 1 , wherein said self-assembling peptides are homogeneous.

8. The method of claim 1 , wherein said self-assembling peptides are selected from the group consisting of:

AKAKAEAEAKAKAEAE,

(SEQ ID NO:1);

AKAEAKAEAKAEAKAE,

(SEQ ID NO:2);

EAKAEAKAEAKAEAKA,

(SEQ ID NO:3);

KAEAKAEAKAEAKAEA,

(SEQ ID NO:4);

AEAKAEAKAEAKAEAK,

(SEQ ID NO:5);

ADADARARADADARAR,

(SEQ ID NO:6);

ARADARADARADARAD,

(SEQ ID NO:7);

DARADARADARADARA,

(SEQ ID NO:8);

RADARADARADARADA,

(SEQ ID NO:9);

ADARADARADARADAR,

(SEQ ID NO:10);

ARADAKAEARADAKAE,

(SEQ ID NO:11);

AKAEARADAKAEARAD,

(SEQ ID NO:12);

ARAKADAEARAKADAE,

(SEQ ID NO:13);

AKARAEADAKARADAE,

(SEQ ID NO:14);

AQAQAQAQAQAQAQAQ,

(SEQ ID NO:15);

VQVQVQVQVQVQVQVQ,

(SEQ ID NO:16);

YQYQYQYQYQYQYQYQ,

(SEQ ID NO:17);

HQHQHQHQHQHQHQHQ,

(SEQ ID NO:18);

ANANANANANANANAN,

(SEQ ID NO:19);

VNVNVNVNVNVNVNVN,

(SEQ ID NO:20);

YNYNYNYNYNYNYNYN,

(SEQ ID NO:21);

HNHNHNHNHNHNHNHN,

(SEQ ID NO:22);

ANAQANAQANAQANAQ,

(SEQ ID NO:23);

AQANAQANAQANAQAN,

(SEQ ID NO:24);

VNVQVNVQVNVQVNVQ,

(SEQ ID NO:25);

VQVNVQVNVQVNVQVN,

(SEQ ID NO:26);

YNYQYNYQYNYQYNYQ,

(SEQ ID NO:27);

YQYNYQYNYQYNYQYN,

(SEQ ID NO:28);

HNHQHNHQHNHQHNHQ,

(SEQ ID NO:29);

HQHNHQHNHQHNHQHN,

(SEQ ID NO:30);

AKAQADAKAQADAKAQAD,

(SEQ ID NO:31);

VKVQVDVKVQVDVKVQVD,

(SEQ ID NO:32);

YKYQYDYKYQYDYKYQYD,

(SEQ ID NO:33);

HKHQHDHKHQHDHKHQHD,

(SEQ ID NO:34);

RARADADARARADADA,

(SEQ ID NO:35);

RADARGDARADARGDA,

(SEQ ID NO:36);

RAEARAEARAEARAEA,

(SEQ ID NO:37);

KADAKADAKADAKADA,

(SEQ ID NO:38);

AEAEAHAHAEAEAHAH,

(SEQ ID NO:39);

FEFEFKFKFEFEFKFK,

(SEQ ID NO:40);

LELELKLKLELELKLK,

(SEQ ID NO:41);

AEAEAKAKAEAEAKAK,

(SEQ ID NO:42);

AEAEAEAEAKAK,

(SEQ ID NO:43);

KAKAKAKAEAEAEAEA,

(SEQ ID NO:44);

AEAEAEAEAKAKAKAK,

(SEQ ID NO:45);

RARARARADADADADA,

(SEQ ID NO:46);

ADADADADARARARAR,

(SEQ ID NO:47);

DADADADARARARARA,

(SEQ ID NO:48);

HEHEHKHKHEHEHKHK,

(SEQ ID NO:49);

VEVEVEVEVEVEVEVEVEVE,

(SEQ ID NO:50);

and

RFRFRFRFRFRFRFRFRFRF,

(SEQ ID NO:51).

9. The method of claim 8 , wherein said method is a treatment for myocardial infarction.

10. The method of claim 8 , wherein said method is a treatment for a wound.

11. The method of claim 8 , wherein said method is a treatment for a damaged ligament, tendon or cartilage.

12. The method of claim 8 , wherein said method is a treatment for damaged nerve tissue.

13. The method of claim 1 , wherein said self-assembling peptides are homogeneous and have a structure selected from the group consisting of: (RARADADA) n (SEQ ID NO:53); (ARARADAD) n (SEQ ID NO:89); and (RADARADA) n (SEQ ID NO:54); wherein n=2-10.

14. The method of claim 13 , wherein said method is a treatment for myocardial infarction.

15. The method of claim 13 , wherein said method is a treatment for a wound.

16. The method of claim 13 , wherein said method is a treatment for a damaged ligament, tendon or cartilage.

17. The method of claim 13 , wherein said method is a treatment for damaged nerve tissue.

18. The method of claim 1 , wherein said self-assembling peptides are homogeneous and have the structure (AEAEAKAK) n (SEQ ID NO:55), wherein n=2-10.

19. The method of claim 1 , wherein said biologically compatible peptide membrane, is made by a process comprising: combining human PDFG with one or more peptides in an aqueous medium at a concentration of monovalent metal cation that is sufficient to promote the self-assembly of said peptides and wherein said one or more peptides are selected from the group consisting of: