Muteins of human lipocalin 2 with affinity for glypican-3 (GPC3) and methods of use thereof
First Claim
1. A lipocalin mutein capable of binding human glypican-3 with an affinity by a KD of about 0.3 nM or lower, wherein the mutein comprises a mutated amino acid residue at sequence position 65 and at least 19 mutated amino acid residues at the sequence positions 36, 40, 41, 49, 52, 68, 70, 72, 73, 76, 77, 79, 81, 87, 96, 100, 103, 105, 106, 125, 127, 132, 134, 136, or 175 in comparison with the linear polypeptide sequence of mature human Lipocalin 2 (hNGAL) (SEQ ID NO:
- 1), and wherein the mutein has at least 80% sequence identity to mature hNGAL (SEQ ID NO;
1).
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Accused Products
Abstract
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.
9 Citations
20 Claims
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1. A lipocalin mutein capable of binding human glypican-3 with an affinity by a KD of about 0.3 nM or lower, wherein the mutein comprises a mutated amino acid residue at sequence position 65 and at least 19 mutated amino acid residues at the sequence positions 36, 40, 41, 49, 52, 68, 70, 72, 73, 76, 77, 79, 81, 87, 96, 100, 103, 105, 106, 125, 127, 132, 134, 136, or 175 in comparison with the linear polypeptide sequence of mature human Lipocalin 2 (hNGAL) (SEQ ID NO:
- 1), and wherein the mutein has at least 80% sequence identity to mature hNGAL (SEQ ID NO;
1). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19, 20)
- 1), and wherein the mutein has at least 80% sequence identity to mature hNGAL (SEQ ID NO;
-
15. A lipocalin mutein comprising an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 5-16 or of a fragment or variant thereof, wherein the fragment or variant comprises mutated amino acid residues of the mutein at the positions 36, 40, 41, 49, 52, 65, 68, 70, 72, 73, 76, 77, 79, 81, 87, 96, 100, 103, 105, 106, 125, 127, 132, 134, 136, and 175 in comparison with the linear polypeptide sequence of mature hNGAL (SEQ ID NO;
1).
- 5-16 or of a fragment or variant thereof, wherein the fragment or variant comprises mutated amino acid residues of the mutein at the positions 36, 40, 41, 49, 52, 65, 68, 70, 72, 73, 76, 77, 79, 81, 87, 96, 100, 103, 105, 106, 125, 127, 132, 134, 136, and 175 in comparison with the linear polypeptide sequence of mature hNGAL (SEQ ID NO;
-
16. A lipocalin mutein comprising an amino acid sequence having at least 95% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 5-16, wherein said mutein comprises a mutated amino acid residue at sequence position 65 in comparison with the linear polypeptide sequence of mature hNGAL (SEQ ID NO;
1).
- 5-16, wherein said mutein comprises a mutated amino acid residue at sequence position 65 in comparison with the linear polypeptide sequence of mature hNGAL (SEQ ID NO;
Specification
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- Resources
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Current AssigneePieris Pharmaceuticals GmbH (Pieris Pharmaceuticals, Inc.)
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Original AssigneePieris Pharmaceuticals GmbH (Pieris Pharmaceuticals, Inc.)
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InventorsHinner, Marlon, Allersdorfer, Andrea, Bel Aiba, Rachida Siham, Aloe, Michaela, Wiedenmann, Alexander, Matschiner, Gabriele, Huelsmeyer, Martin
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Primary Examiner(s)Landsman, Robert S
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Application NumberUS15/575,271Publication NumberTime in Patent Office1,077 DaysField of SearchUS Class CurrentCPC Class CodesA61K 38/00 Medicinal preparations cont...A61K 38/02 Peptides of undefined numbe...A61P 1/16 for liver or gallbladder di...A61P 17/00 Drugs for dermatological di...A61P 35/00 Antineoplastic agentsC07K 14/4725 Proteoglycans, e.g. aggreccanC12N 15/102 Mutagenizing nucleic acidsG01N 33/50 Chemical analysis of biolog...
