Protein Design Labs, Inc.

Glaxo Group Limited

Glaxo Wellcome Inc.

Affymax Technologies, N.v.

Threshold Pharmaceuticals, Inc.

Pdl Biopharma, Inc.

Harold E Selick

Cary L Queen

David A Campbell

Valery V Antonenko

Kevin R Oldenburg

Robert M Gavin

William P Schneider

Gregory A Smith

Alejandro C Zaffaroni

Dennis Solas

Ron L Hale

Man Sung Co

Nicholas F Landolfi

Jian-Xin Duan

Amy Tsai Lu

Kathleen L Coelingh

Arthur H Muir

Stewart Kroll

Damian Handisides

Satoru Ida

John W Tolan

The co-administration of glufosfamide and a glucose lowering drug other than insulin is efficacious in cancer treatment.

Treatment of cancer with glufosfamide in patients not receiving insulin therapy

Novel methods for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about about 3&#x212b; as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.

Humanized immunoglobulins

Novel methods for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about about 3 &angst; as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.

Humanized immunoglobulins and methods of making the same

The invention provides a system and method for synthesizing chemicals onto supports in a parallel manner to produce a combinatorial collection of compounds. The system includes a plurality of middle plates, with each middle plate defining a plurality of reaction zones arranged in a two dimensional array. The reaction zones are adapted to receive a solid support, such as a sheet of membrane, and the middle plates are stackable on each other to form a three dimensional array of reaction zones. The system also includes a pair of end plates, where the middle plates are located between the end plates, and where the end plates include an array of fluid guides corresponding to the array of reaction zones, to allow for selective routing of reagents through the reaction zones.

System and method for solid-phase parallel synthesis of a combinatorial collection of compounds

System and method for solid-phase parallel synthesis of a combinatorial

The invention provides exemplary testing devices, systems, and methods for evaluating the permeation of various chemicals through different types of cells. In one exemplary embodiment, a testing device is provided which comprises a base member and a top member having a plurality of wells which are aligned when the top member is secured to the base member. A membrane sheet which includes at least one layer of cells grown on the sheet is placed between the base member and the top member prior to assembly. Test samples are placed into the wells in the top member and samples are removed from the top and bottom wells at a later time and tested to determine the amount of test sample which permeated through the cells.

Multi-well single-membrane permeation device and methods

The invention provides exemplary testing devices, systems, and methods for evaluating the permeation of various chemicals through different types of cells. In one exemplary embodiment, a testing device is provided which comprises a plate defining at least one well having an open top end. At least one membrane is insertable into the well in a generally vertical orientation to divide the well into separate chambers. The membrane is removable from the well to allow the cells to be grown on the membrane before insertion into the well.

Split multi-well plate and methods

PTH analogs comprising an amino acid sequence that is: SVSEIQLLHNX.sub.1 X.sub.2 X.sub.3 HX.sub.4 X.sub.3 X.sub.3 X.sub.3 X.sub.5 RVX.sub.5 WLR X.sub.4 X.sub.4 LX.sub.3 X.sub.3 VX.sub.1 X.sub.3 X.sub.3 X (SEQ ID NO:10) wherein X.sub.1 is a neutral or positively charged amino acid, X.sub.2 is a neutral amino acid, X.sub.3 is a neutral, positively charged, or negatively charged amino acid, X.sub.4 is a positively charged amino acid, X.sub.5 is a positively charged or negatively charged amino acid, and X is selected from the group consisting of Hol, Ho, a homoserine amide, or the sequence of amino acids comprising residues 35-84 of PTH, have enhanced activity and increased serum half-life as compared with human PTH. The PTH analogs can be produced as fusion proteins in high yields in E. coli host cells; the fusion proteins can be subsequently cleaved to produce the PTH analog.

Compounds with PTH activity

Novel methods for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about about 3 .ANG. as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.

Polynucleotides encoding improved humanized immunoglobulins

The present invention relates to methods of delivering pharmaceutical agents across membranes, including the skin layer or mucosal membranes of a patient. A pharmaceutical agent is covalently bonded to a chemical modifier, via a physiologically cleavable bond, such that the membrane transport and delivery of the agent is enhanced.

Compositions and methods for enhanced drug delivery

Novel methods for producing, and compositions of humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about 3 .ANG. as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.

Novel methods for producing, and compositions of, humanized immunoglobulins having one or more complementarity determining regions (CDR's) and possible additional amino acids from a donor immunoglobulin and a framework region from an accepting human immunoglobulin are provided. Each humanized immunoglobulin chain will usually comprise, in addition to the CDR's, amino acids from the donor immunoglobulin framework that are, e.g., capable of interacting with the CDR's to effect binding affinity, such as one or more amino acids which are immediately adjacent to a CDR in the donor immunoglobulin or those within about 3 .ANG. as predicted by molecular modeling. The heavy and light chains may each be designed by using any one or all of various position criteria. When combined into an intact antibody, the humanized immunoglobulins of the present invention will be substantially non-immunogenic in humans and retain substantially the same affinity as the donor immunoglobulin to the antigen, such as a protein or other compound containing an epitope.

Growing community of inventors

Belmont, CA, United States of America

Harold E Selick