# US 2012/0231002 A1 · Treatment of vasculoproliferative conditions > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2012/0231002 A1 - Document ID: US20120231002A1 - Status: Published application - Kind: A1 - Application number: 13/393,531 - Filed: 2010-09-06 - Published: 2012-09-13 - Earliest claimed: 2009-09-04 - Assignees: UCL Business PLC - Inventors: John Greenwood; Stephen Moss; Xiaomeng Wang - Web page: https://patentgrep.com/patent/US20120231002A1 ## CPC - C07K 16/22: against growth factors {; against growth regulators} - A61P 9/00: Drugs for disorders of the cardiovascular system - A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis - A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers - A61P 27/02: Ophthalmic agents - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C07K 14/47: from mammals - C07K 14/495: Transforming growth factor [TGF] - C07K 16/18: against material from animals or humans - C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} - C12N 15/1136: {against growth factors, growth regulators, cytokines, lymphokines or hormones} - A61K 2039/505: {comprising antibodies} - C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding - C12N 2310/14: interfering nucleic acids [NA] - C12N 2310/141: MicroRNAs, miRNAs - C12N 2320/30: Special therapeutic applications - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract This invention relates to the field of molecular physiology. Specifically, this invention relates to the prevention and/or treatment of vasculoproliferative conditions, especially those of the eye and in the treatment of tumours that exhibit vascular proliferation. Levels of leucine-rich alpha-2-glycoprotein (Lrg1) have been demonstrated to be increased in patients suffering from such conditions and animal models of such conditions. Antagonists of Lrg1 can be used to prevent and/or treat vasculoproliferative conditions. ## Claims ### Claim at position 1 1-27. (canceled) ### Claim 28 A method of treating a vasculoproliferative condition comprising administering to a patient in need thereof an effective amount of an antagonist of Lrg1. ### Claim 29 (depends on 28) A method according to claim 28, wherein said antagonist blocks the interaction between: (a) activin receptor-like kinase 1 (ALK1) and Lrg1; (b) Lrg1 and TGFβ Receptor II (TGFβRII); and/or (c) Lrg1 and TGFβ, in the TGFβ signalling complex. ### Claim 30 (depends on 29) A method according to claim 29, wherein said blocking by said antagonist reduces the interaction between ALK and Lrg1, thereby reducing the interaction between ALK1 and TGFβ Receptor II (TGFβRII) and promoting the interaction between TGFβRII and activin receptor-like kinase 5 (ALK5) such that the effect of TGFβ in the ALK1-activated signalling cascade is reduced relative to the effect of TGFβ in the ALK5-activated signalling cascade. ### Claim 31 (depends on 28) A method according to claim 28, wherein said antagonist comprises an antibody, a double-stranded RNA, an aptamer, or a peptide or peptidomimetic that blocks Lrg1 function. ### Claim 32 (depends on 31) A method according to claim 31, wherein said antagonist is a fragment of Lrg1. ### Claim 33 (depends on 32) A method according to claim 32, wherein said antagonist peptide fragment comprises one or more of sequences L1-24 (SEQ ID NO: 3), L169-192 (SEQ ID NO: 4), and L227-252 (SEQ ID NO: 5), and wherein optionally said antagonist peptide fragment comprises or consists of amino acids 227-252 of Lrg1. ### Claim 34 (depends on 31) A method according to claim 31, wherein said antagonis antibody is a monoclonal antibody. ### Claim 35 (depends on 34) A method according to claim 34, wherein said antagonist monoclonal antibody specifically recognises an epitope within the sequence of L1-24 (SEQ ID NO: 3), L169-192 (SEQ ID NO: 4) or L227-252 (SEQ ID NO: 5) of Lrg1, and wherein optionally said antagonist monoclonal antibody specifically recognises an epitope within L227-252 (SEQ ID NO: 5) of Lrg1. ### Claim 36 (depends on 31) A method according to claim 31 wherein said antagonist double-stranded RNA is a short interfering RNA (siRNA) or microRNA (miRNA). ### Claim 37 (depends on 28) A methodaccording to claim 28 for the treatment of a disorder wherein said vasculoproliferative condition comprises neovascularisation, vascular endothelial cell proliferation, angiogenesis, telangiectasia or microaneurysms. ### Claim 38 (depends on 28) A method according to claim 28, wherein the vasculoproliferative condition is a vasculoproliferative condition of the eye, and wherein optionally the vasculoproliferative condition of the eye is selected from diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity, macular telangiectasia, age-related macular degeneration or choroidal neovascularization. ### Claim 39 (depends on 28) A method according to claim 28, for the treatment of a tumour that exhibits vasculoproliferation, wherein optionally the tumour is selected from brain tumour, breast tumour, kidney tumour, colorectal tumour, lung tumour, prostate tumour, head and neck tumours, stomach tumour, pancreatic tumour, skin tumour, cervical tumour, bone tumour, ovarian tumour, testicular tumour and liver tumours. ### Claim 40 (depends on 28) A method according to claim 28, wherein the Lrg1 antagonist is for use in combination with an antiangiogenic compound. ### Claim 41 (depends on 40) A method according to claim 40, wherein the antiangiogenic compound is an antagonist of vascular endothelial growth factor (VEGF), and wherein optionally said VEGF antagonist is an anti-VEGF antibody. ### Claim 42 A method of identifying antagonists of Lrg1 comprising: (a) providing a candidate antagonist, and (b) determining whether or not said candidate antagonist blocks the function or activity of Lrg1; wherein said candidate antagonist is identified as an antagonist of Lrg1 if blocking of the function or activity of Lrg1 is observed. ### Claim 43 (depends on 42) A method according to claim 42, wherein the Lrg1 antagonist blocks the interaction between: (a) activin receptor-like kinase 1 (ALK1) and Lrg1; (b) Lrg1 and TGFβ Receptor II (TGFβRII); and/or (c) Lrg1 and TGFβ. ### Claim 44 A monoclonal antibody which specifically recognises an epitope within amino acids L1-24 (SEQ ID NO: 3), L169-192 (SEQ ID NO: 4) or L227-252 (SEQ ID NO: 5) and which blocks: (a) Lrg1 activity; or (b) the interaction between: (i) ALK1 and Lrg1; (ii) Lrg1 and TGFβ Receptor II (TGFβRII); and/or (iii) Lrg1 and TGFβ. ### Claim 45 (depends on 44) A method for producing an antibody according to claim 44, comprising: (a) immunising a non-human mammal with an immunogen comprising an epitope within the sequence of L1-24 (SEQ ID NO: 3), L169-192 (SEQ ID NO: 4) or L227-252 (SEQ ID NO: 5) of Lrg1; and (b) obtaining an antibody preparation from said mammal and deriving therefrom monoclonal antibodies that specifically recognise said epitope. ### Claim 46 A method for determining what sites within Lrg1 can be targeted to block the function or activity of Lrg1, comprising: (a) providing peptide fragments of the Lrg1 protein; and (b) determining whether or not said each of said peptide fragments blocks the function or activity of Lrg1. ### Claim 47 (depends on 46) A method according to claim 46, further comprising obtaining antibodies or aptamers that specifically recognise peptide fragments found in step (b) to block function or activity of Lrg1; and optionally further comprising determining whether or not said antibodies or aptamers block the function or activity of Lrg1.