University of California

Biosante Pharmaceuticals, Inc.

Jing Jing Qian

Rajendra Sahai Bhatnagar

Karin Ute Jooss

Jianmin Fang

Craig A Gough

Andrew Simmons

Debbie Farson

Single AAV vector constructs for expression of an immunoglobulin molecule or fragment thereof and methods of making and using the same are described. The AAV vectors comprise a self-processing cleavage sequence between a first and second immunoglobulin coding sequence allowing for expression of a functional antibody molecule using a single promoter. The vector constructs may further include an additional proteolytic cleavage sequence which provides a means to remove the self processing peptide sequence from an expressed immunoglobulin molecule or fragment thereof. The vector constructs find utility in enhanced production of biologically active immunoglobulins or fragments thereof in vitro and in vivo.

AAV vector compositions and methods for enhanced expression of immunoglobulins using the same

Lentivector constructs for expression of recombinant proteins, polypeptides or fragments thereof and methods of making the same are described. The lentivectors typically have a self-processing cleavage sequence between a first and second protein or polypeptide coding sequence allowing for expression of a functional protein or polypeptide under operative control of a single promoter and may further include an additional proteolytic cleavage sequence which provides a means to remove the self-processing cleavage sequence from the expressed protein or polypeptide. The vector constructs find utility in methods relating to enhanced production of biologically active proteins, such as immunoglobulins or fragments thereof in vitro and in vivo.

Methods to express recombinant proteins from lentiviral vectors

Compositions suitable for pharmaceutical administration are provided in which one compound is a small peptide mimic of TGF-&bgr;. More preferably, pharmaceutical compositions of the present invention are formulated as combinations of two components, wherein one component includes a peptide mimic for TGF-&bgr; and the other component is structurally or biologically analogous to a small region of collagen and mimics the conformation recognized by collagen binding species. A particularly preferred combination is A-N-V-A-E-N-A (SEQ ID NO:1) and G-T-P-G-P-Q-G-I-A-G-Q-R-G-V-V (SEQ ID NO:17).

Peptide compositions mimicking TGF-&bgr; activity

TGF-B inhibitors and methods

Small peptide mimics of TGF-.beta., having the general sequence AA.sub.i -AA.sub.i+1 -AA.sub.i+2 followed by AA.sub.i+n shortly thereafter, have been prepared. In this sequence, AA.sub.i is alanine, asparagine, or leucine, AA.sub.i+1 is valine or isoleucine, AA.sub.i+2 is alanine, n is 3, 4, or 5 such that there are n-3 amino acid residues in between AA.sub.i+2 and AA.sub.i+n, and AA.sub.i+n is glutamic acid, aspartic acid, glutamine or asparagine. Because the essential requirement for TGF-.beta. activity is the peptide's ability to form a stable .beta.-bend structure under physiologic conditions, the inventive peptides are collectively referred to as .beta.-bend peptides. Compositions for applications such as tissue repair are also provided that comprise a biocompatible matrix having cytomodulin or a cytomodulin analog admixed with or carried by the matrix.

Peptide compositions with growth factor-like activity

A peptide has been synthesized with the sequence ANVAENA (SEQ ID NO:1). This peptide, designated 'cytomodulin,' is able to mimic a broad range of activities of TGF-.beta.1 in various cell types. Compositions for applications such as tissue repair are provided that comprise a biocompatible matrix having cytomodulin admixed with or carried by the matrix.

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Foster City, CA, United States of America

Jing Jing Qian