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NZ775767B2 - Compositions and methods of inhibiting masp-3 for the treatment of various diseases and disorders - Google Patents

Compositions and methods of inhibiting masp-3 for the treatment of various diseases and disorders Download PDF

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Publication number
NZ775767B2
NZ775767B2 NZ775767A NZ77576717A NZ775767B2 NZ 775767 B2 NZ775767 B2 NZ 775767B2 NZ 775767 A NZ775767 A NZ 775767A NZ 77576717 A NZ77576717 A NZ 77576717A NZ 775767 B2 NZ775767 B2 NZ 775767B2
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New Zealand
Prior art keywords
antibody
seq
antigen
binding fragment
comprises seq
Prior art date
Application number
NZ775767A
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NZ775767A (en
Inventor
W Jason Cummings
Gregory A Demopulos
Thomas Dudler
Hans Wilhelm Schwaeble
Larry W Tjoelker
Christi L Wood
Munehisa Yabuki
Original Assignee
Omeros Corporation
University Of Leicester
Filing date
Publication date
Application filed by Omeros Corporation, University Of Leicester filed Critical Omeros Corporation
Publication of NZ775767A publication Critical patent/NZ775767A/en
Publication of NZ775767B2 publication Critical patent/NZ775767B2/en

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    • C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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    • C09K11/7728—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing rare earth metals containing europium
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
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    • H01F1/0045—Zero dimensional, e.g. nanoparticles, soft nanoparticles for medical/biological use
    • H01F1/0054—Coated nanoparticles, e.g. nanoparticles coated with organic surfactant

Abstract

The present invention relates to MASP-3 inhibitory antibodies and compositions comprising such antibodies for use in inhibiting the adverse effects of MASP-3 dependent complement activation.

Claims (34)

1. An isolated antibody, or antigen-binding fragment thereof, that binds to MASP-3 comprising: a heavy chain variable region comprising a HC-CDR1 set forth as SEQ ID NO:84 (GKWIE); a HC-CDR2 set forth as SEQ ID NO:86 (EILPGTGSTNYNEKFKG) or SEQ ID NO:275 (EILPGTGSTNYAQKFQG); and a HC-CDR3 set forth as SEQ ID NO:88 (SEDV); and a light chain le region comprising a LC-CDR1 set forth as SEQ ID NO:142 (KSSQSLLNSRTRKNYLA), SEQ ID NO:257 (KSSQSLLQSRTRKNYLA); SEQ ID NO:258 (KSSQSLLASRTRKNYLA); or SEQ ID NO:259 (KSSQSLLNTRTRKNYLA), a LC-CDR2 set forth as SEQ ID NO:144 ( WASTRES); and a LC-CDR3 set forth as SEQ ID NO:161 (KQSYNIPT).
2. The antibody or antigen binding nt thereof of claim 1, wherein the dy or antigen-binding fragment is selected from the group ting of a human antibody, a humanized antibody, a chimeric antibody, a murine dy, and an antigen-binding fragment of any of the foregoing.
3. The antibody or antigen-binding nt thereof of claim 1, wherein s aid antibody or antigen binding nt thereof is selected from the group consisting of a single chain antibody, an ScFv, a Fab fragment, an Fab’ fragment, an F(ab’)2 fragment, a univalent antibody lacking a hinge region and a whole antibody.
4. The antibody or antigen-binding fragment thereof of claim 1, further comprising an immunoglobulin constant region.
5. The antibody or antigen binding fragment thereof of claim 1, wherein the antibody or n-binding fragment is zed.
6. The antibody or antigen-binding fragment thereof of claim 1, wherein sa id antibody binds to the serine protease domain of human MASP-3 with an affinity of less than 500 pM.
7. The antibody or antigen-binding fragment thereof of claim 1, wherein said antibody inhibits alternative pathway activation in mammalian blood.
8. An isolated DNA sequence encoding the heavy and/or light chain variable regions of an antibody or antigen-binding fragment thereof from any one of claims 1-7.
9. A cloning or expression vector comprising one or more DNA ces of claim 8.
10. A host cell comprising one or more cloning or sion vectors of claim 9, provided that if the cell is a human cell, it is ex vivo.
11. A process for producing the antibody or antigen-binding fragment of any one of claims 1-7 comprising culturing the host cell of claim 10 and ing the antibody or antigenbinding fragment thereof.
12. A composition sing the antibody or antigen-binding fragment of any one of claims 1-7 and a pharmaceutically acceptable excipient.
13. Use of the composition according to claim 12 comprising a high affinity MASP-3 inhibitory antibody or antigen-binding fragment thereof in the manufacture of a medicament for inhibiting alternative pathway complement activation.
14. The isolated antibody or antigen-binding fragment f of claim 1, wherein the LCCDR1 comprises SEQ ID NO:258.
15. The ed antibody or antigen-binding fragment f of claim 1, wherein the HCCDR2 comprises SEQ ID NO:86.
16. The isolated antibody or antigen-binding nt thereof of claim 1, wherein the HCCDR2 comprises SEQ ID NO:275.
17. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the LCCDR1 comprises SEQ ID NO:142.
18. The isolated antibody or antigen-binding fragment thereof of claim 1, w herein the LCCDR1 comprises SEQ ID NO:257.
19. The isolated antibody or antigen-binding fragment thereof of claim 1, w herein the LCCDR1 comprises SEQ ID NO:259.
20. The isolated antibody or antigen-binding fragment f of claim 1, wherein the HCCDR1 comprises SEQ ID NO:84, the HC-CDR2 comprises SEQ ID NO:86, the HC-CDR3 comprises SEQ ID NO:88, the LC-CDR1 comprises SEQ ID NO:258, the LC-CDR2 comprises SEQ ID NO:144 and the LC-CDR3 comprises SEQ ID NO:161.
21. The ed antibody or antigen-binding fragment thereof of claim 1, wherein the HCCDR1 comprises SEQ ID NO:84, the HC-CDR2 comprises SEQ ID NO:275, the HC-CDR3 comprises SEQ ID NO:88; the LC-CDR1 comprises SEQ ID NO:258, the LC-CDR2 comprises SEQ ID NO:144 and the 3 ses SEQ ID NO:161.
22. The isolated antibody or n-binding fragment thereof of claim 1, wherein the heavy chain le region ses the amino acid sequence set forth as SEQ ID NO:30.
23. The isolated dy or antigen-binding fragment thereof of claim 1, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:45.
24. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:30 and the light chain variable region comprises the amino acid sequence set forth as SEQID NO:45.
25. The isolated antibody or antigen-binding fragment thereof of claim 1, n the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO:254 or SEQ ID NO:255.
26. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:256 or SEQ ID NO:280.
27. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the heavy chain variable region ses SEQ ID NO:254 or SEQ ID NO:255 and the light chain variable region comprises SEQ ID NO:256 or SEQ ID NO:280.
28. The isolated antibody or antigen-binding fragment f of claim 27, wherein the heavy chain le region comprises SEQ ID NO:254 and the light chain variable region comprises SEQ ID NO:256.
29. The isolated antibody or antigen-binding fragment thereof of claim 27, n the heavy chain variable region comprises SEQ ID NO:255 and the light chain variable region comprises SEQ ID NO:256.
30. The isolated antibody or antigen-binding fragment thereof of claim 27, wherein the heavy chain variable region ses SEQ ID NO:254 and the light chain variable region comprises SEQ ID NO: 280.
31. The isolated antibody or antigen-binding fragment thereof of claim 27, wherein the heavy chain variable region comprises SEQ ID NO:255 and the light chain variable region ses SEQ ID NO: 280.
32. The isolated antibody of claim 27, wherein the antibody is selected from the group consisting of a single chain antibody, an ScFv, a Fab fragment, an Fab’ nt, an F(ab’)2 fragment, a ent antibody lacking a hinge region and a whole antibody.
33. The isolated antibody of claim 27, further comprising an immunoglobulin c onstant region.
34. The isolated antibody or antigen-binding fragment thereof of claim 1, substantially as herein bed with reference to any one of the examples and/or
NZ775767A 2017-07-31 Compositions and methods of inhibiting masp-3 for the treatment of various diseases and disorders NZ775767B2 (en)

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