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Compositions containing fusion protein of albumin and analogs thereof, methods for making and using the same

A technology of fusion proteins and analogs, applied in the field of fusion proteins, can solve the problems of less comparative research and the like

Inactive Publication Date: 2019-04-16
NAL PHARM LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, comparative studies on biological and molecular mechanisms between HSA fusion proteins and parent molecules are less reported

Method used

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  • Compositions containing fusion protein of albumin and analogs thereof, methods for making and using the same
  • Compositions containing fusion protein of albumin and analogs thereof, methods for making and using the same
  • Compositions containing fusion protein of albumin and analogs thereof, methods for making and using the same

Examples

Experimental program
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preparation example Construction

[0192] Preparation of somatostatin-albumin fusion protein

[0193] Embodiments of the present invention provide methods for preparing somatostatin-albumin fusion proteins. In one embodiment, the somatostatin-albumin fusion protein of the present invention is prepared by expressing a vector comprising the coding gene and introducing the vector into a suitable host cell. For example, fusion proteins are obtained by expressing a suitable vector in a host such as yeast. In one embodiment, Pichia pastoris GS115 can be used as a suitable expression host, and the vector is pPIC9K. In particular, mammalian cell lines such as CHO or HEK293 can be used as expression hosts.

[0194] The invention also encompasses a plasmid construct capable of expressing an albumin-somatostatin fusion protein, comprising a nucleotide sequence encoding a somatostatin-albumin fusion protein as described in any of the preceding paragraphs. For example, suitable plasmid constructs include, but are not lim...

Embodiment 1

[0209] Example 1: Expression in mammalian systems

Embodiment 1-1

[0210] Example 1-1. Recombinant gene synthesis

[0211] Eight constructs corresponding to the fusion proteins listed in Table 5 were made. First, the gene sequence encoding each fusion protein was synthesized de novo and then inserted into the pcDNA3.1 vector.

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Abstract

The invention is related to fusion proteins of human somatostatin (e.g., SST-14 or SST-28) and human serum albumin, comprising a region at least 85% homologous to human somatostatin and a region at least 85% homologous to human serum albumin or a region with a partial amino acid sequence of human serum albumin, wherein linker peptide sequences may be present between somatostatin and somatostatin moieties or somatostatin and albumin moieties. Also disclosed are constructs wherein the somatostatin moiety contains multiple tandem repeats of a somatostatin sequence. In selected embodiments, the orientation of the somatostatin and albumin moieties can be varied, and such sequences may impact the binding and efficacy of the disclosed fusion proteins. Also disclosed are methods of making and using the aforementioned constructs. The somatostatin-albumin fusion protein demonstrated enhanced stability when incubated in rat plasma in vitro and prolonged plasma half-life in vivo compared with freesomatostatin.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to US Patent Application 15 / 249,346, filed August 26, 2016, the contents of which are incorporated herein by reference. [0003] U.S. Patent Application 15 / 249,346 is a continuation-in-part of PCT / US2016 / 019950, which claims the benefit of priority of U.S. Provisional Patent Application Serial No. US 62 / 121,487, filed February 26, 2015, the contents of each of which are incorporated by reference Incorporated into this article. [0004] U.S. Patent Application 15 / 249,346 also claims priority to Taiwan Patent Application No. 105106088, filed February 26, 2016, which also claims U.S. Provisional Patent Application No. 62 / 121,487, filed February 26, 2015 priority rights, the respective contents of which are incorporated herein by reference. technical field [0005] The present invention relates to fusion proteins comprising somatostatin, or an analog or derivative thereof, a linker or space...

Claims

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Application Information

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IPC IPC(8): A61K38/31A61K38/38A61K38/22A61K38/16C07K14/765C07K14/655C12N15/62A61P5/02
CPCA61K38/00A61P3/10A61P5/02A61P35/00C07K14/655C07K14/76A61K47/643C07K14/765C07K2319/31C12N15/62
Inventor 莫业钧朱振光
Owner NAL PHARM LTD
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