Relaxin analogs and methods of using the same
AssigneeEli Lilly and Company
InventorsPetra Verdino, Stacey Lynn Lee, Xiaojun Wang
Life of this patent
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Abstract
Relaxin (RLN) analogs are disclosed including modifications that increase half-life when compared to native, human RLN, that maintain selectivity to the RXFP1 receptor and that provide in vitro and in vivo stability for improved druggability properties and less immunogenicity. Pharmaceutical compositions also are disclosed that include one or more of the RLN analogs described herein in a pharmaceutically acceptable carrier. Methods of making and using the RLN analogs also are disclosed, especially for treating cardiovascular, pulmonary and/or renal conditions, diseases or disorders.
Claims18
A compound comprising a structure of:
- VHH-L1-A-L2-B,
- VHH-L1-B-L2-A,
- A-L2-B-L1-VHH, or
- B-L2-A-L1-VHH,
- wherein VHH comprises an amino acid sequence selected from the group consisting of SEQ ID NOS:10, 11, 12 and 13,
- wherein A is a relaxin A chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:2, 5 and 8 or a sequence having at least 90% sequence similarity thereto,
- wherein B is a relaxin B chain comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:3, 6 and 9 or a sequence having at least 90% sequence similarity thereto,
- wherein L1 is a first linker comprising an amino acid sequence selected from the group consisting of (GGGGQ)n (SEQ ID NO:14), (PGPQ)n (SEQ ID NO:17) and (PGPA)n (SEQ ID NO:18), and wherein n can be from 1 to 10, and
- wherein L2 is a second linker comprising an amino acid sequence selected from the group consisting of SEQ ID NOS:22, 23 and 67;
- or
- a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.