Angstrom Pharmaceuticals, Inc.

Attenuon, LLC

Tactic Pharma, LLC

University of Michigan

Monopar Therapeutics, Inc.

Andrew P Mazar

Terence R Jones

Robert J Ternansky

Graham Parry

Patricia L Gladstone

Amy Lynn Allan

Fernando Donate

Melissa L P Price

Sean M O'Hare

Fernando Doñate

Stephanie Hopkins

Won Hyung Yoon

Dimitri Coucouvanis

Terrence R Jones

Steven Pirie-Shepherd

Marian Plunkett

Graham C Parry

A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivates, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

Anti-invasive and anti-angiogenic compositions

The present invention relates to antibodies, and antigen-binding fragments thereof, specific for urokinase-type plasminogen activator receptor (uPAR) and uses thereof for the treatment or prevention of cancer. In particular, the antibodies of the invention are specific for a particular epitope on uPAR. These antibodies interfere with uPAR signaling. Such antibodies are used in diagnostic and therapeutic methods, particularly against cancer.

Urokinase-type plasminogen activator receptor epitope, monoclonal antibodies derived therefrom and methods of use thereof

Antibodies or other ligands specific for the binary uPA-uPAR complexes, for ternary complexes comprising uPA-uPAR and for complexes of uPAR and proteins other than uPA such as integrins inhibit the interaction of uPA and uPAR with additional molecules with which the complexed interact. Such antibodies or other ligands are used in diagnostic and therapeutic methods, particularly against cancer.

Ligands binding the complex of urokinase-type plasminogen activator (uPA) and its receptor (uPAR) that inhibit downstream uPAR interactions: identification and use in diagnosis or therapy

The current invention provides novel thiotungstate derivatives, methods of making novel thiotungstate derivatives, pharmaceutical compositions of novel thiotungstate derivatives, methods of using novel thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders and obesity and methods of using pharmaceutical compositions of thiotungstate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-&#x3ba;B dysregulation.

Thiotungstate analogues and uses thereof

A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu [SEQ ID NO:2] or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis. The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

The present invention relates generally to peptides, which inhibit angiogenesis, cell migration, cell invasion and cell proliferation, methods of making peptides, which inhibit angiogenesis, cell migration, cell invasion and cell proliferation, pharmaceutical compositions of these peptides and methods of using these peptides and pharmaceutical compositions of these peptides to treat diseases associated with aberrant vascularization.

Peptides which inhibit angiogenesis, cell migration, cell invasion and cell proliferation, compositions and uses thereof

The current invention provides novel thiomolybdate derivatives, methods of making novel thiomolybdate derivatives, pharmaceutical compositions of novel thiomolybdate derivatives, methods of using novel thiomolybdate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-&#x3ba;B dysregulation and methods of using pharmaceutical compositions of thiomolybdate derivatives to treat diseases associated with aberrant vascularization, copper metabolism disorders, neurodegenerative disorders, obesity or NF-&#x3ba;B dysregulation.

Thiomolybdate analogues and uses thereof

Human kininogen domain 3 (HK-D3) polypeptides and biologically active variants and derivatives of HK-D3 are anti-angiogenic. These molecules are used to inhibit angiogenesis or treat a disease or condition in which angiogenesis is pathogenic. Because of their anti-angiogenic potential, these molecules compounds are useful in the treatment of cancer by inhibiting or reversing the growth of primary or metastatic tumors.

Human kininogen D3 domain polypeptide as an anti-angiogenic and anti-tumor agent

Human kininogen domain 3 (HK-D3) polypeptides and biologically active variants and derivatives of HK-D3 are anti-angiogenic. These molecules are used to inhibit angiogenesis or treat a disease or condition in which angiogenesis is pathogenic. Because of their anti-angiogenic potential, these molecules are useful in the treatment of cancer by inhibiting or reversing the growth of primary or metastatic tumors.

A uPAR-targeting protein or peptide is diagnostically or therapeutically labeled and used in methods of diagnosis of therapy. The labeled protein or peptide preferably has the following properties: it comprises at least 38 amino acid residues, including residues 13-30 of the uPAR-binding site of uPA; competes with labeled DFP-uPA for binding to a cell or molecule that has a binding site for uPA, and has an ICvalue of about 10 nM or less; and is not a fusion protein wherein the uPA peptide is fused to another non-uPA protein or peptide. Preferred molecules are uPA, scuPA, tcuPA, an N-terminal fragment of uPA, residues 1-135, an N-terminal fragment of uPA, residues 1-143, an N-terminal fragment of uPA, residues 1-43; or an N-terminal fragment of uPA, residues 4-43. Detectable labels include a radionuclide, a PET-imageable agent, an MRI-imageable agent, a fluorescer, a fluorogen, a chromophore, a chromogen, a phosphorescer, a chemiluminescer or a bioluminescer. The disclosed methods are used to inhibit cell migration, cell invasion, cell proliferation or angiogenesis, or to induce apoptosis, preferably in the treatment of a subject having a disease or condition associated with undesired cell migration, invasion, proliferation or angiogenesis.

Diagnostic probes and therapeutics targeting uPA and uPAR

A peptide compound having the sequence Lys-Pro-Ser-Ser-Pro-Pro-Glu-Glu &lsqb;SEQ ID NO:2&rsqb; or a substitution variant, addition variant or other chemical derivative thereof inhibits cell invasion, endothelial tube formation or angiogenesis in vitro. A number of substitution variants and addition variants of this peptide, preferably capped at the N- and C-termini, as well as peptidomimetic derivatives, are useful for treating diseases and conditions mediated by undesired and uncontrolled cell invasion and/or angiogenesis. Pharmaceutical compositions comprising the above peptides and derivatives are administered to subjects in need of such treatment in a dosage sufficient to inhibit invasion and/or angiogenesis . The disclosed compositions and methods are particularly useful for suppressing the growth and metastasis of tumors.

uPAR-targeting cyclic peptide compounds have 11 amino acids that correspond to human uPA(20-30) &lsqb;SEQ ID NO:2&rsqb;, or are substitution variants at selected positions. The N and C terminal residues of these peptides are joined by a linking group L, so that the linear dimension between the a carbons of the first and the eleventh amino acids is between about 4 and 12 &angst;ngstrom units. These cyclic peptides may be further conjugated to diagnostic labels or therapeutic moieties such as radionuclides. Such compounds are usefull for targeting uPAR expressed in pathological tissues and for inhibiting the binding of uPA to the uPAR. The pharmaceutical and therapeutic compositions inhibit cell migration, cell invasion, cell proliferation or angiogenesis, or induce apoptosis, and are thus useful for treating diseases or condition associated with undesired cell migration, invasion, proliferation, or angiogenesis, most notably cancer. The cyclic peptides are also used to detect and isolate cells expressing uPAR.

Growing community of inventors

San Diego, CA, United States of America

Andrew P Mazar