Pieris Pharmaceuticals Gmbh

Pieris Ag

Astrazeneca Ab

Daiichi Sankyo Company, Limited

Other

Gabriele Matschiner

Andreas Hohlbaum

Martin Huelsmeyer

Andrea Allersdorfer

Alexander Wiedenmann

Marlon Hinner

Rachida Siham Bel Aiba

Stefan Trentmann

Arne Skerra

Bradley Lunde

Hans-Juergen Christian

Tohru Takahashi

Ryuji Hashimoto

Christine Rothe

Alexandra Baehre

Klaus Kirchfeld

Kristian Hobolt Jensen

Michaela Gebauer

Dominik Hinz

Sabine Rauth

Shinji Yamaguchi

Shane Olwill

Futoshi Nara

Kazufumi Kubota

Tomohiro Nishizawa

Mamoru Otoyo

Sakiko Takahashi

Michaela Aloe

Takahide Aburatani

Chikako Nagasaki

Mitsuhiro Makino

Laurent Audoly

Steffen Schlehuber

Hendrik Gille

Martin Pöhlchen

Rachida Bel Aiba

Klaus Kirchfled

Lauren Audoly

Kristian Jensen

The present invention relates to a novel library for the generation of muteins and to novel muteins derived from human lipocalin 2 (Lcn2, hNGAL) and related proteins that bind a given target with detectable affinity. The invention also relates to corresponding nucleic acid molecules encoding such a mutein and to a method for their generation. The invention further relates to a method for producing such a mutein. For example, such muteins may serve to bind and deplete pathological forms of natural biomolecules such as the amyloid beta peptide in Alzheimer's disease or may target the fibronectin extra-domain B, which is associated with tumor neovasculature.

Muteins of human lipocalin 2 (Lcn2, hNGAL) with affinity for a given target

The present disclosure provides hNGAL muteins that bind CGRP and can be used in various application including pharmaceutical applications, for example, migraine. The present disclosure also concerns methods of making one or more muteins described herein as well as compositions and combinations comprising one or more of such muteins. The present disclosure further relates to nucleic acid molecules encoding such muteins and to methods for generation of such muteins and nucleic acid molecules. In addition, the application discloses therapeutic and/or diagnostic uses of these muteins as well as compositions and combinations comprising one or more of such muteins.

Proteins specific for calcitonin gene-related peptide

The disclosure provides a multi-specific polypeptide with a first moiety specific for a tumor-associated antigen on tumor cell surface and a second moiety specific for an immune checkpoint protein, which multi-specific polypeptide can be useful for biasing a T-cell-mediated response to a tumor micro-environment. For example, the polypeptide may contain: a) a first binding domain, for example, a full-length antibody or an antigen-binding domain of an antibody, specifically recognizing a tumor-associated antigen on tumor cell surface, and b) a second binding domain, such as a lipocalin mutein, capable of stimulating T-cell proliferation e.g., by inhibiting a protein receptor that down-regulates the immune system. The first binding domain may be genetically linked (i.e., peptide bond at its N- or C-terminus) to the second binding domain. The multispecific polypeptide also may contain a third or yet additional specific binding moieties, any of which can specifically bind a distinct immune checkpoint protein. The polypeptide may contain an Fc region of an antibody or of an antigen-binding domain thereof and simultaneously engage (1) a T cell receptor complex of a T cell, (2) a tumor-associated antigen on tumor cell surface, while (3) preserving the Fc function of the Fc region to Fc receptor-positive cell. The polypeptide is useful for the induction of an anti-tumor immunity in humans and/or animals. The disclosure also provides thermal-stable lipocalin muteins specific for CTLA-4. The disclosure further relates to a process for the production of the polypeptide or muteins as well nucleic acids encoding for the polypeptide or muteins, to vectors comprising the same and to host cells comprising the vector. In another aspect, the disclosure provides for a pharmaceutical composition comprising the polypeptide or muteins and medical uses of the polypeptide or muteins.

Multi-specific polypeptide useful for localized tumor immunomodulation

The present invention relates to novel muteins derived from human tear lipocalin, which bind to IL 4 receptor alpha. The sequences of the muteins comprise particular combinations of amino acids. In particular a mutated amino acid residue is present at any one or more of the sequence positions 27, 28 30, 31, 33, 53, 57, 61, 64, 66, 80, 83, 104-106 and 108 of the linear polypeptide sequence of the mature human tear lipocalin. A mutated amino acid residue is also present at any 2 or more of the sequence positions 26, 32, 34, 55, 56, 58 and 63 of the linear polypeptide sequence of the mature human tear lipocalin. The invention also provides a corresponding nucleic acid molecule encoding such a mutein and a method for producing such a mutein and its encoding nucleic acid molecule.

Tear lipocalin muteins binding IL-4 r alpha

The present disclosure relates to novel, specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins preferably are muteins of a lipocalin protein, more preferably of lipocalin 2 (Lcn2 or NGAL). Present disclosure also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, present disclosure also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

Nucleic acid molecules encoding muteins of human lipocalin 2 with affinity for glypican-3 (GPC3)

Muteins of human lipocalin 2 (Lcn2,hNGAL) with affinity for a given target

The present invention relates to novel, specific-binding therapeutic and/or diagnostic polypeptides directed against the target of Swiss Prot Q16552 and novel, specific-binding therapeutic and/or diagnostic polypeptides directed against the target of Swiss Prot Q9NPF7. In addition, the present invention relates to novel, specific-binding therapeutic and/or diagnostic polypeptides directed against one or both of Swiss Prot Q16552 and Swiss Prot Q9NPF7. The invention also relates to nucleic acid molecules encoding such polypeptides and to methods for generation of such polypeptides and nucleic acid molecules. In addition, the invention is directed to compositions comprising the polypeptides, and therapeutic and/or diagnostic uses of these polypeptides.

Interleukin-17A-specific and interleukin-23-specific binding polypeptides and uses thereof

Muteins of human lipocalin 2 with affinity for glypican-3 (GPC3) and methods of use thereof

Tear lipocalin muteins binding IL-4 R alpha

The present invention relates to novel muteins derived from human tear lipocalin having affinity to human c-Met receptor tyrosin kinase (c-Met). The invention also refers to a corresponding nucleic acid molecule encoding such a mutein and to a method for its generation. The invention further refers to a method for producing such a mutein. Finally, the invention is directed to a pharmaceutical composition comprising such a lipocalin mutein as well as to various uses of the mutein.

Muteins with tear lipocalin having affinity to human c-met receptor tyrosine kinase and methods for obtaining the same

The present invention relates to novel muteins derived from human tear lipocalin, which bind to IL 4 receptor alpha. The sequences of the muteins comprise particular combinations of amino acids. In particular a mutated amino acid residue is present at any one or more of the sequence positions 27, 28, 30, 31, 33, 53, 57, 61, 64, 66, 80, 83, 104-106 and 108 of the linear polypeptide sequence of the mature human tear lipocalin. A mutated amino acid residue is also present at any 2 or more of the sequence positions 26, 32, 34, 55, 56, 58 and 63 of the linear polypeptide sequence of the mature human tear lipocalin. The invention also provides a corresponding nucleic acid molecule encoding such a mutein and a method for producing such a mutein and its encoding nucleic acid molecule.

The present disclosure relates to novel lipocalin muteins which bind to PCSK9. The disclosure also provides corresponding nucleic acid molecules encoding lipocalin muteins and methods for producing lipocalin muteins as well as their encoding nucleic acid molecules.

Nucleic acid molecules encoding muteins of human tear lipocalin which bind PCSK9

Muteins of human lipocalin 2 (LcnC,hNGAL) with affinity for a given target

Described are specific-binding therapeutic and/or diagnostic proteins directed against Glypican-3 (GPC3), which proteins include muteins of a lipocalin protein, such as lipocalin 2 (Lcn2 or NGAL). The invention also relates to nucleic acid molecules encoding such proteins and to methods for generation and use of such proteins and nucleic acid molecules. Accordingly, the invention also is directed to pharmaceutical and/or diagnostic compositions comprising such lipocalin proteins, including uses of these proteins.

Muteins of human lipocalin 2 with affinity for glypican-3 (GPC-3)

Growing community of inventors

Munich, Germany

Gabriele Matschiner