Claims for Patent: 10,072,065

Summary for Patent: 10,072,065

Title:	Peptide-mediated delivery of immunoglobulins across the blood-brain barrier
Abstract:	Provided herein are materials and methods for delivering immunoglobulins (e.g. therapeutic immunoglobulins) across the blood-brain barrier.
Inventor(s):	Sarkar; Gobinda (Rochester, MN), Jenkins; Robert B. (Rochester, MN), Curran; Geoffry L. (Rochester, MN)
Assignee:	Mayo Foundation for Medical Education and Research (Rochester, MN)
Application Number:	15/246,232
Patent Claims:	1. A peptide comprising the sequence: TABLE-US-00006 (SEQ ID NO: 1) A.sub.p-L.sub.n-B.sub.m wherein: (a) A is an immunoglobulin affinity ligand comprising the sequence H-W-R-G-W-Z (SEQ ID NO:26); (b) L is a linker; and (c) B is a blood-brain barrier agent comprising the sequence: TABLE-US-00007 (SEQ ID NO: 3) L-R-X1-R-X2-X3-X4-H-L-R-X5-X6-X7-K-R-L-X8-R-D-X9; wherein: X1 is selected from the group consisting of A, L, S, and V; X2 is selected from the group consisting of L and M; X3 is selected from the group consisting of A and S; X4 is selected from the group consisting of N, S, and T; X5 is selected from the group consisting of K and N; X6 is selected from the group consisting of L, M, and V; X7 is selected from the group consisting of R and P; X8 is selected from the group consisting of L and M; X9 is selected from the group consisting of A and L; n is an integer from 0 to 50; m is an integer from 1 to 3; and p is an integer from 1 to 4. 2. The peptide of claim 1, wherein the immunoglobulin affinity ligand can non-covalently binds a therapeutic immunoglobulin. 3. The peptide of claim 2, wherein the therapeutic immunoglobulin is an IgG immunoglobulin. 4. The peptide of claim 1, wherein p is 1. 5. The peptide of claim 1, wherein the linker is one or more hydrophilic amino acids. 6. The peptide of claim 5, wherein the linker is one or more lysines. 7. The peptide of claim 6, wherein n is 4. 8. The peptide of claim 1, wherein the blood-brain barrier agent is TABLE-US-00008 (SEQ ID NO: 4) L-R-V-R-L-A-S-H-L-R-K-L-R-K-R-L-L-R-D-A. 9. A complex comprising: (a) the peptide of claim 1; and (b) a therapeutic immunoglobulin. 10. The complex of claim 9, wherein the blood-brain barrier agent is TABLE-US-00009 (SEQ ID NO: 4) L-R-V-R-L-A-S-H-L-R-K-L-R-K-R-L-L-R-D-A. 11. The complex of claim 9, wherein the therapeutic immunoglobulin is selected from the group consisting of cetuximab, bococizumab, dinutuximab, racotumomab, ralpancizumab, and bevacizumab. 12. The complex of claim 9, where the peptide comprises the sequence: TABLE-US-00010 (SEQ ID NO: 42) H-W-R-G-W-Z-K-K-K-K-L-R-V-R-L-A-S-H-L-R-K-L-R-K-R- L-L-R-D-A. 13. A method of transporting a therapeutic immunoglobulin across the blood-brain barrier of a patient, the method comprising: (a) administering to the patient an effective amount of a peptide comprising the sequence: TABLE-US-00011 (SEQ ID NO: 1) A.sub.p-L.sub.n-B.sub.m wherein: i. A is an immunoglobulin affinity ligand comprising the sequence H-W-R-G-W-Z (SEQ ID NO:26); ii. L is a linker; and iii. B is a blood-brain barrier agent comprising the sequence: TABLE-US-00012 (SEQ ID NO: 3) L-R-X1-R-X2-X3-X4-H-L-R-X5-X6-X7-K-R-L-X8-R- D-X9; wherein: X1 is selected from the group consisting of A, L, S, and V; X2 is selected from the group consisting of L and M; X3 is selected from the group consisting of A and S; X4 is selected from the group consisting of N, S, and T; X5 is selected from the group consisting of K and N; X6 is selected from the group consisting of L, M, and V; X7 is selected from the group consisting of R and P; X8 is selected from the group consisting of L and M; X9 is selected from the group consisting of A and L; n is an integer from 0 to 50; m is an integer from 1 to 3; and p is an integer from 1 to 4; and (b) concurrently administering to the patient an effective amount of the therapeutic immunoglobulin. 14. The method of claim 13, wherein the immunoglobulin affinity ligand non-covalently binds the therapeutic immunoglobulin. 15. The method of claim 14, wherein the therapeutic immunoglobulin is an IgG immunoglobulin. 16. A method of treating a neurological disorder in a patient, the method comprising: (a) administering to the patient an effective amount of a peptide comprising the sequence: TABLE-US-00013 (SEQ ID NO: 1) A.sub.p-L.sub.n-B.sub.m wherein i. A is an immunoglobulin affinity ligand comprising the sequence H-W-R-G-W-Z (SEQ ID NO:26); ii. L is a linker; and iii. B is a blood-brain barrier agent comprising the sequence: TABLE-US-00014 (SEQ ID NO: 3) L-R-X1-R-X2-X3-X4-H-L-R-X5-X6-X7-K-R-L-X8-R-D-X9; wherein: X1 is selected from the group consisting of A, L, S, and V; X2 is selected from the group consisting of L and M; X3 is selected from the group consisting of A and S; X4 is selected from the group consisting of N, S, and T; X5 is selected from the group consisting of K and N; X6 is selected from the group consisting of L, M, and V; X7 is selected from the group consisting of R and P; X8 is selected from the group consisting of L and M; X9 is selected from the group consisting of A and L; n is an integer from 0 to 50; m is an integer from 1 to 3; and p is an integer from 1 to 4; and (b) concurrently administering to the patient an effective amount of a therapeutic immunoglobulin. 17. The method of claim 16, wherein the neurological disorder is chosen from: meningitis, epilepsy, multiple sclerosis, neuromyelitis optica, late-stage neurological trypanosomiasis, Parkinson's, progressive multifocal leukoencephalopathy, De Vivo disease, Alzheimer's disease, HIV Encephalitis, addiction, and cancer.

Details for Patent 10,072,065

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2035-08-24
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2035-08-24
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2035-08-24
United Therapeutics Corporation	UNITUXIN	dinutuximab	Injection	125516	03/10/2015		2035-08-24