Wayne C Widdison

6441163, Aug 27, 2002

May 31, 2001

09/867598

Ravi V. J. Chari - Newton MA
Wayne C. Widdison - Somerville MA

Immunogen, Inc. - Cambridge MA

C07D49112

540458, 540462

The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

6716821, Apr 6, 2004

Dec 21, 2001

10/024290

Robert Yongxin Zhao - Watertown MA
Michael Louis Miller - Somerville MA
Wayne Charles Widdison - Somerville MA
Ravi V. J. Chari - Newton MA

Immunogen Inc. - Cambridge MA

A61K 3170

514 34, 514229, 514449, 5303917, 536 64, 540462, 549510

Cytotoxic agents bearing a polyethylene glycol (PEG) linking group having a terminal active ester, cytotoxic conjugates comprising one or more cytotoxic agents linked to a cell-binding agent via PEG linking groups, and methods for producing both are disclosed. A therapeutic composition comprising a therapeutically-effective amount of one of the cytotoxic conjugates of the present invention, and a method of killing selected cell populations comprising contacting target cells, or tissue containing target cells, with an effective amount of one of the cytotoxic conjugates, are also disclosed.

6913748, Jul 5, 2005

Aug 5, 2003

10/633616

Wayne Charles Widdison - Somerville MA, US

Immunogen, Inc. - Cambridge MA

A61K039/395
C07D401/00

4241781, 5303911, 540456, 540462, 5462784, 5462787

Disclosed is a method of making conjugates of cell binding agents and small molecule drugs comprising reacting a cell binding agent with a bifunctional cross-linking moiety to thereby provide the cell binding agent with a reactive disulfide group and then reacting the modified cell binding agent with a small molecule drug comprising a free thiol group. Bifunctional cross-linking moieties are also disclosed.

RE39151, Jun 27, 2006

Apr 10, 2003

10/410143

Ravi Vankeepuram Jagannatha Chari - Newton MA, US
Wayne Charles Widdison - Somerville MA, US

Immunogen, Inc. - Cambridge MA

C07D 491/12
C07D 498/06

540456, 540458

The present invention provides a process for the preparation and purification of thiol-containing maytansinoids comprising the steps of: (1) reductive hydrolysis of a maytansinoid C-3 ester with a reducing agent selected from the group consisting lithium trimethoxyaluminum hydride (LiAl (OMe)H), lithium triethoxyaluminum hydride (LiAl(OEt)H), lithium tripropoxyaluminum hydride (LiAl (OPr)H), sodium trimethoxyaluminum hydride (NaAl (OMe)H), sodium triethoxyaluminum hydride (NaAl(OEt)H) and sodium tripropoxyaluminum hydride (NaAl(OPr)H) to yield a maytansinol; (2) purifying the maytansinol to remove side products when present; (3) esterifying the purified maytansinol with a carboxylic acid to yield a mixture of an L- and a D-aminoacyl ester of maytansinol; (4) separating the L-aminoacyl ester of maytansinol from the reaction mixture in (3); (5) reducing the L-aminoacyl ester of maytansinol to yield a thiol-containing maytansinoid; and (5) purifying the thiol-containing maytansinoid.

7276497, Oct 2, 2007

May 20, 2004

10/849136

Ravi V. J. Chari - Newton MA, US
Wayne C. Widdison - Somerville MA, US

C07D 498/18
A61K 31/535

5142295, 540456

New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

7301019, Nov 27, 2007

Jan 19, 2006

11/334478

Wayne C. Widdison - Somerville MA, US
Ravi V. J. Chari - Newton MA, US

Immunogen, Inc. - Cambridge MA

C07D 491/12
C07D 498/06

540456

Improved processes for the preparation and purification of maytansinoid esters, especially thiol and disulfide-containing maytansinoids are described. In one aspect the process comprises a process of making a maytansinoid ester comprising forming an anion of maytansinol or a maytansinoid bearing a free C-3 hydroxyl moiety and reacting the anion with an activated carboxyl compound to thereby produce the maytansinoid ester.

7368565, May 6, 2008

Jun 5, 2002

10/161651

Ravi V. J. Chari - Newton MA, US
Wayne C. Widdison - Somerville MA, US

Immunogen Inc. - Cambridge MA

A61K 39/00

540458, 4241841

The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

7432088, Oct 7, 2008

Jan 19, 2005

11/037104

Cynthia Kuo - Lujou, TW
Graham S. Byng - Snohomish WA, US
Wayne C. Widdison - Somerville MA, US

Immunogen Inc. - Waltham MA

C12P 17/18
C12P 17/16
C12N 1/20

435119, 435118, 4352521, 4352532, 540460, 540462

A process of the large-scale fermentation of a highly productive ansamitocin-producing strains. A method for isolating crude ansamitocins. A method for purifying ansamitocins.