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Last Updated: April 26, 2024

Claims for Patent: 9,285,372


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Summary for Patent: 9,285,372
Title:Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins
Abstract: Methods and compositions for identifying D-peptidic compounds that specifically bind target proteins are provided. Aspects of the methods include screening libraries of 20 residue or more L-peptidic compounds for specific binding to 40 residue or more D-target proteins. Once a L-peptidic compound has been identified that specifically binds to the D-target protein, the D-enantiomer of that compound may be produced.
Inventor(s): Ault-Riche; Dana (San Francisco, CA), Kent; Stephen B. H. (San Francisco, CA), Sidhu; Sachdev S. (Toronto, CA), Uppalapati; Maruti (Toronto, CA)
Assignee: Reflexion Pharmaceuticals, Inc. (San Francisco, CA) The Governing Council of the University of Toronto (Toronto, CA)
Application Number:13/294,078
Patent Litigation and PTAB cases: See patent lawsuits and PTAB cases for patent 9,285,372
Patent Claims:1. A method comprising: a) contacting a 50 residue or more D-target protein with a library of 50 residue or more distinct .beta.1 domain of Protein G (GB1) L-peptidic compounds comprising a 4.beta.-1.alpha. structural motif, wherein the compounds of the library are described by the formula .beta.1-.beta.2-.alpha.1-.beta.3-.beta.4 wherein .beta.1, .beta.2, .beta.3 and .beta.4 are independently beta-strand domains; and .beta.1, .beta.2, .alpha.1, .beta.3, .beta.4 are connected independently by linking sequences of between 1 and 10 residues in length, wherein the compounds of the library have at least 8 mutations outside of the .beta.1-.beta.2 and .beta.3-.beta.4 regions, wherein the compounds of the library have at least 10 conserved residues in the .beta.1-.beta.2 and .beta.3-.beta.4 regions, wherein the library is a phage display library, wherein the compounds of the library comprise between 20 and 80 residues; b) identifying a L-peptidic compound of the library that specifically binds to the D-target protein; and c) producing the D-peptidic compound of the identified L-peptidic compound.

2. The method according to claim 1, wherein the 50 residue or more D-target protein is selected from the group consisting of a hormone, a growth factor, a receptor, an enzyme, a cytokine, an osteoinductive factor, a colony stimulating factor and an immunoglobulin.

3. The method according to claim 2, wherein the 50 residue or more D-target protein is selected from the group consisting of a growth hormone, a bovine growth hormone, an insulin like growth factor, a human growth hormone, a parathyroid hormone, a proinsulin, a prorelaxin, a glycoprotein hormone, a leutinizing hormone, a hemapoietic growth factor, a fibroblast growth factor, a prolactin, a placental lactogen, a tumor necrosis factor, a mullerian inhibiting substance, an inhibin, an activin, a VEGF protein, an integrin, a RANKL protein, a NGF protein, an insulin-like growth factor-I or II, an erythropoietin, an osteoinductive factor, an interferon, a colony stimulating factor, an interleukin, an IgE protein, a bone morphogenetic protein, LIF, a SCF protein, kit-ligand, a SH2 domain containing protein, a SH3 domain containing protein, an IL-4 protein, an IL-8 protein, an apoptosis protein, a hepatocyte growth factor, a hepatocyte growth factor receptor, neutravidin, and a maltose binding protein.

4. The method according to claim 3, wherein the D-target protein is selected from the group consisting of a VEGF protein, a RANKL protein, a NGF protein, a TNF-alpha protein, a 3BP2 protein, an ABL protein, a Src protein, an IgE protein, a BLyS protein, a PCSK9 protein, an Ang2 protein, and a Clostridium difficile Toxin A or B protein.

5. The method according to claim 1, wherein the compounds of the library comprise between 30 and 80 residues.

6. The method according to claim 5, wherein the compounds of the library comprise between 40 and 70 residues.

7. The method according to claim 6, wherein the compounds of the library comprise between 45 and 60 residues.

8. The method according to claim 7, wherein the compounds of the library comprise between 52 and 58 residues.

9. The method according to claim 1, wherein the D-target protein comprises 75 or more residues.

10. The method according to claim 9, wherein the D-target protein comprises 100 or more residues.

11. The method according to claim 10, wherein the D-target protein comprises 125 or more residues.

12. The method according to claim 11, wherein the D-target protein comprises 150 or more residues.

13. The method according to claim 12, wherein the D-target protein comprises 175 or more residues.

14. The method according to claim 13, wherein the D-target protein comprises 200 or more residues.

15. The method according to claim 1, wherein the compounds of the library comprise a scaffold domain and a variable domain that comprises at least 10 mutations.

16. The method according to claim 15, wherein the variable domain comprises at least 14 mutations.

17. The method according to claim 1, further comprising screening the D-peptidic compound for specific binding to the L-enantiomer of the D-target protein.

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