Patents.us
Patents/USRE050320

USRE050320No. USRE050320reissueGranted 3/4/2025

Claims (18)

Claim 1 (Independent)

1. A synthetic apolipoprotein E(ApoE)-mimicking peptide comprising a receptor binding domain of ApoE and a lipid-associating peptide, wherein the synthetic ApoE-mimicking peptide comprises a fatty acid moiety, a ω-amino fatty acid moiety, or an acetylated ω-amino fatty acid moiety, wherein the lipid-associating peptide comprises a class A amphipathic helical domain, wherein the fatty acid moiety is a saturated fatty acid moiety, wherein the receptor binding domain of ApoE is on the N-terminus of the synthetic ApoE-mimicking peptide, and wherein the saturated fatty acid moiety , ω-amino fatty acid moiety, or acetylated ω-amino fatty acid moiety is at the N-terminus of the receptor binding domain of ApoE.

Show 17 dependent claims
Claim 2 (depends on 1)

2. The peptide of claim 1 , wherein the synthetic ApoE-mimicking peptide comprises the acetylated ω-amino fatty acid moiety.

Claim 3 (depends on 2)

3. The peptide of claim 2 , wherein the acetylated ω-amino fatty acid moiety is Ac-Aha.

Claim 4 (depends on 2)

4. The peptide of claim 2 , wherein the Ac-Aha is at the N-terminus of the peptide.

Claim 5 (depends on 1)

5. The peptide of claim 1 , wherein the synthetic ApoE-mimicking peptide comprises the ω-amino fatty acid moiety.

Claim 6 (depends on 5)

6. The peptide of claim 5 , wherein A synthetic apolipoprotein E(ApoE)-mimicking peptide comprising a lipid-associating peptide, a receptor-binding domain of ApoE at the N-terminus of the ApoE-mimicking peptide, and a w-amino fatty acid moiety at the N-terminus of the receptor-binding domain, wherein the lipid-associating peptide comprises a class A amphipathic helical domain, and the ω-amino fatty acid moiety is 4-amino-butanoyl, 6-amino-caproyl, 8-amino-octanoyl, 10-amino-decanoyl, 12-amino-lauroyl, 14-amino-myristoyl, 14-amino-myristoleoyl, 16-amino-palmitoyl, 18-amino-stearoyl, 18-amino-oleoyl, 16-amino-palmitoleoyl, 18-amino-linoleoyl, 18-amino- linolenoyl 18-amino-linolenoyl , or 20-amino-arachidonoyl.

Claim 7 (depends on 6)

7. The peptide of claim 6 , wherein the ω-amino group is acetylated.

Claim 8 (depends on 1)

8. The peptide of claim 1 , wherein the fatty acid moiety, the ω-amino fatty acid moiety, or the acetylated ω-amino fatty acid moiety is at the N-terminus of the peptide.

Claim 9 (depends on 1)

9. The peptide of claim 1 , wherein the class A amphipathic-helical domain is DWLKAFYDKVAEKLKEAF (SEQ ID NO:5), DWLRAFYDKVAEKLREAF (SEQ ID NO:618), DWLRALYDKVAEKLREAL (SEQ ID NO:619), DLLRALYDKVAEKLREAW (SEQ ID NO:620), or FAEKLKEAVKDYFAKLWD (SEQ ID NO:616).

Claim 10 (depends on 1)

10. The peptide of claim 1 , wherein said synthetic ApoE-mimicking peptide is protected using an amide group at the C-terminus.

Claim 11 (depends on 1)

11. The peptide of claim 1 , wherein the receptor binding domain of ApoE is LRKLRKRLLR (SEQ ID NO:4), LRRLRRRLLR (SEQ ID NO:11), LRKMRKRLMR (SEQ ID NO:7), RLTRKRGLK (SEQ ID NO:13), LRRMRRRLMR (SEQ ID NO:621), or RLTRRRGK (SEQ ID NO:622).

Claim 12 (depends on 1)

12. The peptide of claim 1 , wherein the synthetic ApoE-mimicking peptide is Ac-Aha-hE18A-NH2 or Ac-Aha-[R]hE18A-NH2.

Claim 13 (depends on 1)

13. A pharmaceutical composition, comprising the synthetic apolipoprotein E-mimicking peptide of claim 1 and a pharmaceutically acceptable carrier.

Claim 14 (depends on 1)

14. The peptide of claim 1 , wherein the A synthetic ApoE-mimicking peptide that is butanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 623); hexanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 624); octanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 625); decanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 626); lauroyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 627); myristoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 628); palmitoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 629); stearoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 630); palmitoleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 631); arachidoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 632); behenoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 633); oleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 634); ricinoleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 635); linolenoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 636); vacceoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 637); gadoleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 638); erucoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 639); cetoleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 640); nervonoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 641); adrenoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 642); α-linolenoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 643); γ-linolenoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 644); EPA-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 645); DHA-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 646) , 4-amino-butanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 648); 6-amino-hexanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 649); 8-amino-octanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 650); 10-amino-decanoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 651); 12-amino-lauroyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 652); 14-amino-myristoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 653); 16-amino-palmitoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 654); 16-amino-palmitoleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 655); 18-amino-stearoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 656); 18-amino-oleoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 657); 18-amino-linolenoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 658); or 20-amino-arachidoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH 2 (SEQ ID NO: 659).

Claim 15 (depends on 14)

15. The synthetic ApoE-mimicking peptide of claim 14 , wherein the synthetic ApoE-mimicking peptide is oleovl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH2 (SEQ ID NO: 634).

Claim 16 (depends on 14)

16. The synthetic ApoE-mimicking peptide of claim 14 , wherein the synthetic ApoE-mimicking peptide is octano 1-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH2 (SE ID NO: 625).

Claim 17 (depends on 14)

17. The synthetic ApoE-mimicking peptide of claim 14 , wherein the synthetic ApoE-mimicking peptide is myristoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH2 (SEQ ID NO: 628).

Claim 18 (depends on 14)

18. The synthetic ApoE-mimicking peptide of claim 14 , wherein the synthetic ApoE-mimicking peptide is palmitoyl-LRRLRRRLLRDWLKAFYDKVAEKLKEAF-NH2 (SEQ ID NO: 629).

Full Description

No description text available for this patent.

Citations

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