P-cadherin as a target for anti-cancer therapy
AssigneeChiron Corporation
InventorsChristoph Reinhard, Julie Klinger, Ann Jefferson, Jaime Escobedo, Fillipo Randazzo, Jill Winter, Robert Goodson, Weimin Qi
Life of this patent
Estimating the term…
Abstract
Method of treating or diagnosing cancers involving P-cadherin expression are provided using ligands that target P-cadherin, especially human anti-P-cadherin antibodies. Also provided are screens for identifying anti-P-cadherin antibodies having therapeutic activity.
Claims64
A method of treating a cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of at least one P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of inhibiting the migration, adhesion and/or proliferation of a P-cadherin expressing cancer comprising administering a subject in need of such treatment an effective amount of a P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of treating or preventing a digestive cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of at least one P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of inhibiting the migration, adhesion and/or proliferation of digestive cancer cells that express P-cadherin comprising administering an effective amount of a P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of treating a colon or colorectal cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of at least one P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of inhibiting the migration, adhesion and/or proliferation of colon cancer cells in a subject in need of such treatment comprising administering an effective amount of a P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of treating or preventing a cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of at least one P-cadherin antagonist or P-cadherin-binding antibody fragment, optionally conjugated to a therapeutic agent.
A method of treating or preventing a cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of a ribozyme or antisense oligonucleotide that modulates P-cadherin expression, optionally conjugated to a therapeutic agent.
A method of treating or preventing a digestive cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of at least one anti-P-cadherin antibody or P-cadherin-binding antibody fragment, optionally conjugated to a therapeutic agent.
A method of treating or preventing a digestive cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of at least one ribozyme or antisense oligonucleotide that modulates P-cadherin expression, optionally conjugated to a therapeutic agent.
A method of treating or preventing a colon or colorectal cancer characterized by the overexpression and/or upregulation of P-cadherin comprising the administration of an effective amount of an anti-P-cadherin antibody or P-cadherin-binding antibody fragment, optionally conjugated to a therapeutic agent.
A human, chimeric or humanized anti-P-cadherin antibody which is suitable for treatment of a cancer characterized by P-cadherin overexpression and/or upregulation, optionally conjugated to a therapeutic agent.
A transgenic non-human animal that expresses a recombinant antibody that specifically binds P-cadherin.
A transgenic animal that expresses a recombinant human antibody that specifically binds P-cadherin.
A ribozyme that modulates P-cadherin expression in a P-cadherin expressing cell.
An antisense oligonucleotide that modulates P-cadherin expression in a P-cadherin expressing cell.
A pharmaceutical composition adopted for the treatment of a cancer characterized by the overexpression and/or upregulation of P-cadherin that comprises a pharmaceutically effective amount of at least one human, chimeric or humanized antibody or antibody fragment that specifically binds P-cadherin and a pharmaceutically acceptable carrier.
A pharmaceutical composition adopted for the treatment of a cancer characterized by the overexpression and/or upregulation of P-cadherin comprising a pharmaceutically effective amount of at least one ribozyme or antisense oligonucleotide that modulates P-cadherin expression and a pharmaceutically acceptable carrier.
A recombinant host cell that expresses a human, humanized or chimeric antibody or antibody fragment that specifically binds P-cadherin.
A method of determining the presence of a cancer involving the overexpression and/or upregulation of P-cadherin comprising:
- (i) obtaining a cell sample from a patient to be diagnosed for the presence or absence of a cancer involving the overexpression and/or upregulation of P-cadherin;
- (ii) determining the level of expression of P-cadherin in said cell sample;
- (iii) comparing said levels of P-cadherin expression to a normal cell sample;
- and
- (iv) correlating said level of P-cadherin expression in said patient cell sample relative to the normal cell sample to a positive or negative diagnosis of a cancer associated with the overexpression and/or upregulation of P-cadherin.
A method of inhibiting the proliferation of colon cancer in a subject in need of such treatment comprising administering an effective amount of an antibody to P-cadherin or a fragment thereof that specifically binds P-cadherin.
A method of inhibiting at least one of the adhesion, proliferation and/or migration of a cancer cell associated with upregulation of P-cadherin comprising administering an inhibitory effective amount of at least one P-cadherin antagonist, optionally conjugated to a therapeutic agent.
A method of inhibiting at least one of the adhesion, migration and/or proliferation of colon cancer cells characterized by upregulation of P-cadherin comprising administering to a subject in need of such treatment an inhibitory effective amount of at least one P-cadherin antibody, optionally conjugated to a therapeutic agent.
A method of inhibiting at least one of the adhesion, migration and/or proliferation of a cancer cell associated with upregulation of P-cadherin comprising administering an inhibitory effective amount of at least one P-cadherin antibody, optionally conjugated to a therapeutic agent.
A method of inhibiting at least one of the adhesion, migration and/or proliferation of colon cancer cells characterized by upregulation of P-cadherin comprising administering to a subject in need of such treatment an inhibitory effective amount of at least one antibody that specifically binds P-cadherin, optionally conjugated to a therapeutic agent.
A method of therapy comprising preferentially targeting P-cadherin overexpressing tumor tissues by administration of a P-cadherin binding antibody or antibody fragment.
The method of any one of claims 4449 wherein said antibody is attached to a toxin.
A method of screening for an anti-P-cadherin antibody having potential therapeutic activity comprising screening a population of anti-P-cadherin antibodies for those that inhibit proliferation of tumor cells.
A method of screening for an anti-P-cadherin antibody having potential therapeutic activity comprising screening a population of anti-P-cadherin antibodies for those that induce apoptosis of tumor cells.
A method of screening for an anti-P-cadherin antibody having potential therapeutic activity comprising screening a population of anti-P-cadherin antibodies for those that posses ADCC and/or CDC activity.
A method of screening for an anti-P-cadherin antibody having potential therapeutic activity comprising screening a population of anti-P-cadherin antibodies for those that inhibit tumor cell migration
A method of screening for an anti-P-cadherin antibody having potential therapeutic activity comprising screening a population of anti-P-cadherin antibodies for those that inhibit metastasis.
A method for screening for an anti-P-cadherin antibody that binds to the EC1 domain comprising screening a population of anti-P-cadherin antibodies for those that bind the EC1 domain.
A method for screening for an anti-P-cadherin antibody that possess one of the following properties by screening population of anti-P-cadherin antibody population for an antibody that possesses at least one of the properties:
- (i) interferes with P-cadherin strand formation;
- (ii) interferes with cis dimer formation of P-cadherin proteins;
- (iii) blocks or inhibits calcium binding by P-cadherin;
- and
- (iv) interferes with P-cadherin domain alignment.
Dependencies are inferred from the claim text.