Wyeth Holdings Corporation

Wyeth

Regeneron Pharmaceuticals, Inc.

American Cyanamid Company

Arthur Kunz

Nitin Krishnaji Damle

Mark Edward Ruppen

Justin Keith Moran

Andrew George Popplewell

John W Simpson

Joseph Thomas Rubino

John Francis DiJoseph

Nishith Merchant

Eugene Joseph Vidunas

Paul David Robbins

Neera Jain

Lioudmila Tchistiakova

Davinder Gill

Kimberly Ann Marquette

Erwin R Boghaert

Kiran Khandke

Philip Ross Hamann

Thomas Nittoli

Kodangattil R Sreekumar

Philip R Hamann

Irwin J Hollander

Sreekumar R Kodangattil

Martin P Kunstmann

John McLean Simpson

Kodangattil Raman Sreekumar

Lioudmile Tchistiakova

The present disclosure relates to conjugates comprising biologically active molecules linked to a multimeric antigen-binding compound or a multimeric immunoglobulin via a linker. The disclosure further provides reagents and methods of manufacturing the conjugates and the linkers. The disclosure also provides compositions comprising the conjugates, methods of modifying abnormal cell growth and methods of treatment using the conjugates or the compositions.

Biologically active molecule conjugates, reagents and methods of manufacture, and therapeutic uses

Antibody-drug conjugates, their preparation and their therapeutic use

Anti-5T4 antibodies, anti-5T4 antibody/drug conjugates, and methods for preparing and using the same.

Anti-5T4 antibodies and uses thereof

Methods for preparing monomeric cytotoxic drug/carrier conjugates with a drug loading significantly higher than in previously reported procedures and with decreased aggregation and low conjugate fraction (LCF) are described. Cytotoxic drug derivative/antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described. Monomeric calicheamicin derivative/anti-CD22 antibody conjugates, compositions comprising the conjugates and uses of the conjugates are also described.

Calicheamicin derivative-carrier conjugates

A method is provided for preparing monomeric calicheamicin derivative/carrier conjugates with higher drug loading/yield and decreased aggregation. These conjugates are prepared by incubating a calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution, a cosolvent selected from the group consisting of propylene glycol, ethanol, DMSO, and combinations thereof, and an additive comprising at least one C.sub.6 -C.sub.18 carboxylic acid having a pH in the range from about 4.0 to 8.5 and at a temperature ranging from about 25.degree. C. to about 37.degree. C. for a period of time ranging from about 15 minutes to about 24 hours, and recovering monomeric calicheamicin derivative/carrier conjugates. Alternatively, the conjugates can be prepared by incubating the calicheamicin derivative and a proteinaceous carrier in a solution comprising a non-nucleophilic, protein-compatible, buffered solution and a cosolvent comprising t-butanol.

Methods for the preparation of monomeric calicheamicin

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Arthur Kunz