99 results about "Integrin antagonist" patented technology

The present invention relates to novel Fc variants of antibodies that immunospecifically binds to Integrin αvβ3. The Fc variants comprise a variable region that immunospecifically binds to Integrin αvβ3 and a Fc region that further comprises at least one novel amino acid residue which may provide for enhanced effector function. More specifically, this invention provides Fc variants that have modified binding affinity to one or more FcγR and / or C1q. Additionally, the Fc variants have altered antibody dependent cell-mediated cytotoxicity (ADCC) and / or complement dependent cytotoxicity (CDC) activity. The invention further provides methods and protocols for the application of said Fc variants of an antibody that immunospecifically binds to Integrin αvβ3, particularly for therapeutic purposes.

The present invention provides methods and compositions for inhibiting the biological activity of integrins, for inhibiting endothelial cell migration. and for inhibiting angiogenesis. In particular, the invention provides compositions comprising ADAM disintegrin domains and methods for using said compositions. In preferred embodiments the methods and compositions of the invention are used to inhibit angiogenesis and to treat diseases or conditions mediated by angiogenesis.

The present invention provides methods of augmenting B cell depletion by promoting intravascular access of B cell subsets sequestered in lymphoid tissues rendering the B cells sensitive to killing mediated by the B cell depleting agent. One method of promoting intravascular access is by the use of integrin antagonists. Methods of treating B cell disorders by this approach is also provided.

This invention relates to inhibition of αv integrins, especially αvβ3 and αvβ6 integrins, by specific antagonists, preferably non-peptidic antagonists, related compounds and compounds with comparable specificity, that downregulate fibrogenesis by inhibiting cell migration and production of pro-fibrogenic molecules (e.g., collagens, TIMP-1) and cytokines (e.g., CTGF) by activated hepatic stellate cells / myofibroblasts, activated epithelia and endothelia. These antagonists alone or in combination with other agents can effectively prevent, mitigate or even reverse development of advanced fibrosis, such as fibrosis / cirrhosis of the liver and fibrosis of other organs, such as lungs, kidneys, intestine, pancreas, skin and arteries.

The present invention provides methods of augmenting B cell depletion by promoting intravascular access of B cell subsets sequestered in lymphoid tissues rendering the B cells sensitive to killing mediated by the B cell depleting agent. One method of promoting intravascular access is by the use of integrin antagonists. Methods of treating B cell disorders by this approach is also provided.

Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula:wherein X is bromo or iodo, or pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods and intermediates useful for making the pharmaceutical agents and methods of using the pharmaceutical agents are also provided.

Antagonists of alpha 4 integrin / alpha 4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their alpha 4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.

A compound of formula (I) or a salt thereofwhereinR1 represents a hydrogen atom, a methyl group or a ethyl groupR2 represents a hydrogen atom or a fluorine atomR3 represents a hydrogen atom, a methyl group or an ethyl group.

The invention relates to compounds of the Formula 1 and to pharmaceutically acceptable salts and solvates thereof, wherein A, X2, X4, X5 and X1 are as defined herein. The invention also relates to methods of treating abnormal cell growth in mammals by administering the compounds of Formula 1 and to pharmaceutical compositions for treating such disorders which contain the compounds of Formula 1.

Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula:wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods and intermediates useful for making the pharmaceutical agents and methods of using the pharmaceutical agents are also provided.

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The present invention relates to fluorinated compounds of formula I and methods of synthesizing these compounds. The present invention also relates to pharmaceutical compositions containing the fluorinated compounds of the invention, and methods of treating macular degeneration, diabetic retinopathy (DR), macular edema, diabetic macular edema (DME), and macular edema following retinal vein occlusion (RVO), by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The present invention relates to methods for treating multiple sclerosis by administering therapeutically effective amounts of an alpha-fetoprotein polypeptide (or a biologically active fragment, derivative, or analog thereof) and an integrin antagonist (e.g., natalizumab) to a patient in need thereof. Also disclosed are compositions and kits that comprise therapeutically effective amounts of an alpha-fetoprotein polypeptide (or a biologically active fragment, derivative, or analog thereof) and an integrin antagonist (e.g., natalizumab).

The present invention relates to novel substituted indole compounds that are antagonists of alpha V (αv) integrins, for example αvβ3 and αvβ5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by αvβ3 and αvβ5 integrins, including such conditions as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, D, X, W, a, m, n, i, j, k and v are defined herein.

Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula:wherein X is bromo or iodo, or pharmaceutically acceptable salts thereof. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods and intermediates useful for making the pharmaceutical agents and methods of using the pharmaceutical agents are also provided.

The present invention relates to methods and compositions designed for the treatment, management or prevention of cancer. The methods of the invention comprise the administration of an effective amount of one or more antagonists of Integrin αVβ3 alone or in combination with the administration of an effective amount of one or more other agents useful for cancer therapy. The invention also provides pharmaceutical compositions comprising one or more antagonists of Integrin αVβ3 and / or one or more other agents useful for cancer therapy. In particular, the invention is directed to methods of treatment and prevention of cancer by the administration of a therapeutically or prophylactically effective amount of one or more antagonists of Integrin αVβ3 alone or in combination with standard and experimental therapies for treatment or prevention of cancer. Also included are methods for screening for epitope-specific Integrin αVβ3 antagonists which can be used according to the methods of the invention. In addition, methods for facilitating the use of Integrin αVβ3 antagonists in the analysis of Integrin αVβ3 expression in biopsies of animal model and clinical study samples are also contemplated.

Antagonists of α4 integrin / α4 integrin ligand adhesion, which inhibit the biological effects of such adhesion are described and methods for their use are detailed. Such antagonists are useful in suppressing bone destruction associated with multiple myeloma. The homing of multiple myeloma cells to bone marrow and their α4 integrin-dependent release of bone-resorbing factors, resulting in bone destruction in patients with multiple myeloma, is inhibited.

The invention relates to compounds of formula I:wherein R1, R2, and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula I for use in the manufacture and delivery of conjugated moieties such as small molecules, peptides, nucleic acids, fluorescent moieties, and polymers which are linked to LFA-1 integrin antagonists to target cells expressing LFA-1.

The invention features methods for identifying compounds capable of inhibiting the binding of a selected integrin to a selected ligand which naturally binds the selected integrin.

The invention relates to compounds of formula (I): wherein R1, R2, and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula (I) for use in the manufacture and delivery of conjugated moieties such as small molecules, peptides, nucleic acids, fluorescent moieties, and polymers which are linked to alpha-V-beta-integrin antagonists to target cells expressing alpha-V-beta-3.

The present invention involves the pharmaceutical field, including integrin antagonists, which have the capacities of inhibiting angiogenesis of tumors, binding integrin. These antagonists are a kind of polypeptide, which was modified by polyethylene glycol and after modification, it can be used to treat tumors. The sequence and structure of these antagonists is mPEG-SC20k-Ile-Val-Arg-Arg-Ala-Asp-Arg-Ala-Ala-Val-Pro-Gly-Gly-Gly-Gly-Arg-Gly-Asp, which demonstrates it is scientific, reasonable and feasible in tumor treatment and greatly expands the treatment spectrum. It can provide new ideas and perspectives for drug development and has significant social and market value.

αvβ3 Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic αvβ3 integrin antagonist.

Disclosed herein are novel pharmaceutical agents which are useful as integrin receptor antagonists that mediate the pathologic processes of angiogenesis and fibrosis and as such are useful in pharmaceutical compositions and in methods for treating conditions mediated by these integrins by inhibiting or antagonizing these integrins. The novel pharmaceutical agents include those of the formula:wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such pharmaceutical agents. Methods and intermediates useful for making the pharmaceutical agents and methods of using the pharmaceutical agents are also provided.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising the continuous administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agent or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered together with said ligands, such as chemotherapeutic agents and / or radiation therapy, in isolated organ perfusion. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone.

The present invention relates to biphenyl and biphenyl-analogous compounds, their preparation and use as pharmaceutical compositions, as integrin antagonists and in particular for the production of pharmaceutical compositions for the treatment and prophylaxis of cancer, arteriosclerosis, restenosis, osteolytic disorders such as osteoporosis and ophthalmic diseases. The compounds according to the invention have formula (1) wherein R<1>, R<2>, U, V, A, B, W, R<3>, C and R<4> have the meaning as defined in the claims.

The invention relates to a combination therapy for the treatment of tumors and tumor metastases comprising administration of integrin ligands, preferably integrin antagonists, together with co-therapeutic agents or therapy forms that have synergistic efficacy when administered consecutively with said ligands, such as chemotherapeutic agents and or radiation therapy. The therapy results in a synergistic potential increase of the inhibition effect of each individual therapeutic on tumor cell proliferation, yielding more effective treatment than found by administering an individual component alone, concurrently or not in the dosage regime of the present invention.