Merck Patent Gmbh

The Dow Chemical Company

Medtronic, Inc.

Smith + Nephew

Tim Jones

Francis Joseph Carr

Graham Carter

Matthew Baker

Francis J Carr

Stephen Williams

Anita Anne Hamilton

Lisa Lynn Shafer

Koen Hellendoorn

James Peter Gregson

John Watkins

Dawn Ann Bembridge

Edward Colby

Julian Scarfe

Mary M Bendig

George Peter Lomonossoff

Alaric Naiman

John Emil Johnson

Colin D Ager

Marian Hanlon

Mary Bendig

Marian Longstaff

Mark Priest

Humanized anti-A&#x3b2; antibodies derived from a murine antibody directed to a N-terminal epitope of A&#x3b2; are described. The humanized antibodies have reduced or no human T cell epitopes and bind A&#x3b2; with an affinity similar to that of the murine antibody.

Humanized anti-amyloid beta antibodies

The present invention relates a modified human interferon beta (INF&#x3b2;) which is less immunogenic than human INF&#x3b2; (SEQ ID NO: 1) when administered in vivo to a human. The modified human INF&#x3b2; comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by an amino acid residue substitution selected from the group consisting of L57A, L57C, L57D L57E, L57G, L57H, L57K, L57N, L57P, L57Q, L57R, L57S, and L57T and an additional substitution selected from the group consisting of the H140A, H140C, H140G, and H140P.

Modified interferon beta with reduced immunogenicity

The invention concerns human interferon alpha and in particular modified forms of interferon alpha 2 with improved properties. The improved proteins contain amino acid substitutions at specific positions that confer increased relative activity in biological assays. The invention provides also modified interferon alpha with improved biological activity concomitant with reduced immunogenic potential in the protein. The improved proteins are intended for therapeutic use in the treatment of diseases in humans.

Fusion proteins of interferon alpha muteins with improved properties

This invention relates to a novel approach for identification of T-cell epitopes, that give rise to an immune reaction in a living host. By means of this novel method biological compounds can be generated which have a no or at least a reduced immunogenicity when exposed to the immune system of a given species and compared with the relevant non-modified entity. Thus the invention relates also to novel biological molecules, especially proteins and antibodies, obtained by the method according to the invention.

Method for identification of t-cell epitopes and use for preparing molecules with reduced immunogenicity

A method of preparing a modified granulocyte colony stimulating factor (G-CSF) protein having reduced immunogenicity relative to human G-CSF comprises the steps of (i) identifying one or more potential T-cell epitopes within the amino acid sequence of human G-CSF (SEQ ID NO:); (ii) designing at least one sequence variant of at least one potential T-cell epitope identified in step (i), wherein the sequence variant eliminates or substantially reduces the MHC class II binding activity of the potential T-cell epitope; (iii) preparing, by recombinant DNA techniques, at least one modified G-CSF protein including a sequence variant designed in step (ii); (iv) evaluating at least one modified G-CSF protein prepared in step (iii) for G-CSF activity and immunogenicity; and (v) selecting a modified G-CSF protein evaluated in step (iv) that has substantially the same therapeutic G-CSF biological activity as, but substantially less immunogenicity than, human G-CSF.

Method of preparing a modified granulocyte colony stimulating factor (G-CSF) with reduced immunogenicity

A modified interferon beta (INF&#x3b2;) is provided, which is less immunogenic than human INF&#x3b2; (SEQ ID NO: 1) when administered to a human in vivo. The modified INF&#x3b2; comprises an amino acid residue sequence that differs from SEQ ID NO: 1 by a substitution at one or more residues of SEQ ID NO: 1. Preferred substitutions are at residues selected from the group consisting of residue 50, 59, 60, 62, 63, 66, 67, 69, 70, 125, 126, 129, 130, 132, 133, and 138. Examples of suitable substitutions include F50A, L57A, I59A, Y60N, M62A, L63A, I66T, F67H, I69A, F70A, Y125A, Y126A, I129A, L130A, Y132S, L133A, Y138H, and Y138A.

The present invention relates to the expression of peptides on viral particles, and more particularly to the expression of peptides on the interior or the viral capsid. Methods are described for modifying viruses so that exogenous epitopes are expressed on the interior of the viral capsid. Viruses that can be modified include (+) stranded RNA viruses, especially plant (+) stranded RNA viruses such as the cowpea mosaic virus. Internal expression is especially useful for the expression of hydrophobic epitopes. The modified viral particles also find use as vaccines and as such are capable of eliciting an immune response.

Viral particles with exogenous internal epitopes

The present invention relates to antibodies which are directed to the EGF receptor (HER1) to be administered especially to humans and in particular for therapeutic use in tumors. The antibodies are modified whereby the modification results in a reduced propensity for the antibody to elicit an immune response upon administration to the human subject. The invention in particular relates to the modification of anti-EGFR antibody 425 in its different forms and fragments thereof to result in Mab 425 variants that are substantially non-immunogenic or less immunogenic than any non-modified counterpart when used in vivo.

Modified anti-EGFR antibodies with reduced immunogenicity

Mucin peptide epitopes are inserted into the coat protein of a plant virus (e.g., a comovirus such as CPMV) having a beta-barrel structure at an immunogenically effective site, such as in a loop connecting beta sheets or at/near the C-terminus. The resulting chimaeric virus particles are extremely immunogenic, giving better results than KLH conjugation and not requiring the addition of exogenous adjuvant. They are effective at mucosal surfaces, particularly when administered intranasally.

Chimaeric plant viruses with mucin peptides

The invention relates to assembled particles of a plant virus containing a foreign peptide insert in the coat protein of the virus. The site of the insert is preferably free from direct sequence repeats flanking the insert. The invention relates to a method of production of the particles and their use, in particular in vaccines.

Modified plant viruses as vectors of heterologous peptides

An extension indicator is provided for determining a predetermined extension applied to an extensibly deformable article such as medical bandage used in compression therapy. The indicator includes first ( ) and second ( ) co-operating members, each adapted to be secured to an extensibly deformable article ( ). One of the members is more extensible than the other and each member ( ) bears visual indicia ( ) which upon extension of the more extensible member, are adapted to align with each other to indicate a predetermined extension of the more extensible member.

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Babraham, United Kingdom

Tim Jones