Dyax Corporation

Genzyme Corporation

Protein Engineering Corporation

Kirin Beer Kabushiki Kaisha

Bruce Lindsay Roberts

Robert Charles Ladner

Arthur Charles Ley

William Markland

Rachel B Kent

Sonia Kosow Guterman

William M Siders

William Harold Brondyk

Srinivas Shankara

Johanne Kaplan

Shiro Kataoka

Sonia Kosow Gutterman

Johanne M Kaplan

Beverly Teicher

Tomoyuki Tahara

Nakayuki; Honma

The present invention relates to humanized immunoglobulins, mouse monoclonal antibodies and chimeric antibodies that have binding specificity for human CD52. The present invention further relates to a humanized immunoglobulin light chain and a humanized immunoglobulin heavy chain. The invention also relates to isolated nucleic acids, recombinant vectors and host cells that comprise a sequence which encodes a humanized immunoglobulin or immunoglobulin light chain or heavy chain, and to a method of preparing a humanized immunoglobulin. The humanized immunoglobulins can be used in therapeutic applications to treat, for example, autoimmune disease, cancer, non-Hodgkin's lymphoma, multiple sclerosis and chronic lymphocytic leukemia.

Anti-human CD52 immunoglobulins

The invention provides methods of treating lupus in a patient with an anti-CD52 antibody. Also includes are methods of increasing infiltration of regulatory T cells to affected sides of the patient's body, methods of reducing urine protein and/or albumin levels and methods of depleting lymphocytes to alleviate lupus symptoms.

Methods and compositions for treating lupus

In order to obtain a novel binding protein against a chosen target, DNA molecules, each encoding a protein comprising one of a family of similar potential binding domains and a structural signal calling for the display of the protein on the outer surface of a chosen bacterial cell, bacterial spore or phage (genetic package) are introduced into a genetic package. The protein is expressed and the potential binding domain is displayed on the outer surface of the package. The cells or viruses bearing the binding domains which recognize the target molecule are isolated and amplified. The successful binding domains are then characterized. One or more of these successful binding domains is used as a model for the design of a new family of potential binding domains, and the process is repeated until a novel binding domain having a desired affinity for the target molecule is obtained. In one embodiment, the first family of potential binding domains is related to bovine pancreatic trypsin inhibitor, the genetic package is M13 phage, and the protein includes the outer surface transport signal of the M13 gene III protein.

Directed evolution of novel binding proteins

The invention relates, in part, to a library of chimeric proteins, each chimeric protein including a mini-protein between about eight and about forty amino acids long, wherein the mini-protein has a single disulfide bond formed by a pair of invariant cysteines and has only two cysteines. The chimeric protein also includes at least a portion of an outer surface protein of a genetic package, wherein the chimeric protein is displayed on the outer surface of the genetic package. The invention also includes, in part, a mixture of nucleic acids that encode a library of the invention. The invention also includes, in part, a process for identifying proteins with a desired binding activity against a target, the process including screening a library of chimeric proteins of the invention; and identifying the chimeric protein. The invention, in part, also includes chimeric proteins expressed by a library of the invention.

Directed evolution of disulfide-bonded micro-proteins

Method of recovering a nucleic acid encoding a proteinaceous binding domain which binds a target material

Mutants of Kunitz domain 1 (ITI-D1) of human inter-&#x3b1;-trypsin inhibitor (ITI), are useful as inhibitors of human neutrophil elastase. Mutants characterized by one or more of the following substitutions (numbered to correspond to bovine pancreatic trypsin inhibitor, the archetypal Kunitz domain) are of particular interest: (a) Val15 or Ile15, (b) Ala16, (c) Phe18, (d) Pro19, (e) Arg1, (f) Pro2, and/or (g) Phe4.

ITI-D1 Kunitz domain mutants as HNE inhibitors

Certain Kunitz domain derived proteins which bind and inhibit human neutrophil elastase with a K.sub.i of less than 10 picomolar are described.

Engineered human-derived kunitz domains that inhibit human neutrophil

Viruses expressing chimeric binding proteins

Growing community of inventors

Milford, MA, United States of America

Bruce Lindsay Roberts