Methods of selecting compstatin mimetics

• US 10,407,466 B2
• Filed: 01/06/2017
• Issued: 09/10/2019
• Est. Priority Date: 10/08/2005
• Status: Active Grant

• Current Assignee: Apellis Pharmaceuticals, Inc.
• Original Assignee: Apellis Pharmaceuticals, Inc.
• Inventors: Deschatelets, Pascal, Olson, Paul, Francois, Cedric
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/400,831
• Publication Number:
  US 20170349631A1
• Time in Patent Office: 977 Days
• CPC Class Codes: A61F 9/0008 Introducing ophthalmic products into the ocular cavity or retaining products therein putting in contact lenses A61F9/0061; introducing or retaining media in cavities of the body in general A61M31/00
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/10 Peptides having 12 to 20 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/12 Cyclic peptides , e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 49/0008 Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0051 Ocular inserts, ocular implants
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/14 Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2319/01 : containing a localisation/targetting motif
• CPC Class Codes: C07K 7/08 : having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68
• CPC Class Codes: G01N 2333/4704 : Inhibitors; Supressors
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 2500/20 : cell-free systems
• CPC Class Codes: G01N 33/6872 : Intracellular protein regulatory factors and their receptors, e.g. including ion channels

Abstract

The present invention features the use of compstatin and complement inhibiting analogs thereof for treating and/or preventing age related macular degeneration and other conditions involving macular degeneration, choroidal neovascularization, and/or retinal neovascularization. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a second therapeutic agent. The invention also provides compositions comprising compstatin or a complement inhibiting analog thereof and a gel-forming material, e.g., soluble collagen, and methods of administering the compositions.

Claims

1. A method comprising steps of:

(i) providing a three-dimensional structure of C3 or a portion thereof to which compstatin binds;

(ii) computationally docking a plurality of molecular structures with the structure of C3;

(iii) selecting a molecular structure from the plurality of molecular structures that binds to substantially the same site as that to which compstatin binds;

(iv) testing the ability of a test compound having the molecular structure selected in step (iii) to bind to C3, wherein the testing comprises contacting C3 with labeled compstatin (SEQ ID NO;

     8) in the presence of different concentrations of the test compound; and

(v) identifying the test compound as a compstatin mimetic if it diminishes binding of the labeled compstatin to C3 by at least 25%.

2. The method of claim 1, wherein the test compound is identified as a candidate compstatin mimetic if it diminishes binding of the labeled compstatin to C3 by at least 50%.