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NZ775769B2 - Compositions and methods of inhibiting masp-3 for the treatment of various diseases and disorders - Google Patents
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NZ775769B2 - 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

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Publication number
NZ775769B2
NZ775769B2 NZ775769A NZ77576917A NZ775769B2 NZ 775769 B2 NZ775769 B2 NZ 775769B2 NZ 775769 A NZ775769 A NZ 775769A NZ 77576917 A NZ77576917 A NZ 77576917A NZ 775769 B2 NZ775769 B2 NZ 775769B2
Authority
NZ
New Zealand
Prior art keywords
seq
antibody
set forth
chain variable
variable region
Prior art date
Application number
NZ775769A
Other versions
NZ775769A (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
Priority to NZ785975A priority Critical patent/NZ785975B2/en
Publication of NZ775769A publication Critical patent/NZ775769A/en
Publication of NZ775769B2 publication Critical patent/NZ775769B2/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y25/00—Nanomagnetism, e.g. magnetoimpedance, anisotropic magnetoresistance, giant magnetoresistance or tunneling magnetoresistance
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    • C01—INORGANIC CHEMISTRY
    • C01F—COMPOUNDS OF THE METALS BERYLLIUM, MAGNESIUM, ALUMINIUM, CALCIUM, STRONTIUM, BARIUM, RADIUM, THORIUM, OR OF THE RARE-EARTH METALS
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    • C01P2002/80—Crystal-structural characteristics defined by measured data other than those specified in group C01P2002/70
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    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • 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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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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    • C07K2317/565—Complementarity determining region [CDR]
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    • C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
    • C07K2317/734—Complement-dependent cytotoxicity [CDC]
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    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
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    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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    • C09K11/00—Luminescent materials, e.g. electroluminescent or chemiluminescent
    • C09K11/08—Luminescent materials, e.g. electroluminescent or chemiluminescent containing inorganic luminescent materials
    • C09K11/77—Luminescent materials, e.g. electroluminescent or chemiluminescent containing inorganic luminescent materials containing rare earth metals
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    • C09K11/00—Luminescent materials, e.g. electroluminescent or chemiluminescent
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    • C09K11/77—Luminescent materials, e.g. electroluminescent or chemiluminescent containing inorganic luminescent materials containing rare earth metals
    • C09K11/7728—Luminescent materials, e.g. electroluminescent or chemiluminescent containing inorganic luminescent materials containing rare earth metals containing europium
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    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • 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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    • C12Y304/21—Serine endopeptidases (3.4.21)
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    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H01F1/0036—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties showing low dimensional magnetism, i.e. spin rearrangements due to a restriction of dimensions, e.g. showing giant magnetoresistivity
    • 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 (25)

1. An isolated antibody, or antigen-binding fragment thereof, that binds to human MASP-3 comprising: a) a heavy chain variable region comprising a HC-CDR1 set forth as SEQ ID NO:72, a HC-CDR2 set forth as SEQ ID NO:74, and a HC-CDR3 set forth as SEQ ID NO:76; and a light chain variable region comprising a LC-CDR1 set forth as SEQ ID NO:153, a LC-CDR2 set forth as SEQ ID NO:155, and a LC-CDR3 set forth as SEQ ID NO:157; b) a heavy chain variable region comprising a HC-CDR1 set forth as SEQ ID NO:72, a HC-CDR2 set forth as SEQ ID NO:74, and a 3 set forth as SEQ ID NO:76; and a light chain variable region sing a LC-CDR1 set forth as SEQ ID NO:263, a LC-CDR2 set forth as SEQ ID NO:155, and a 3 set forth as SEQ ID NO:157; or c) a heavy chain variable region comprising a HC-CDR1 set forth as SEQ ID NO:79, a HC-CDR2 set forth as SEQ ID NO:74, and a HC-CDR3 set forth as SEQ ID NO:82; and a light chain variable region comprising a LC-CDR1 set forth as SEQ ID NO:159, a LC-CDR2 set forth as SEQ ID NO:155, and a LC-CDR3 set forth as SEQ ID NO:160.
2. The ed antibody or antigen-binding fragment thereof of Claim 1, wherein the HCCDR1 comprises SEQ ID NO:72, the HC-CDR2 comprises SEQ ID NO:74, the HC-CDR3 comprises SEQ ID NO:76, the LC-CDR1 comprises SEQ ID NO:153, the LC-CDR2 ses SEQ ID NO:155 and the LC-CDR3 comprises SEQ ID NO:157.
3. The isolated antibody or antigen-binding fragment thereof of Claim 1, wherein the HCCDR1 ses SEQ ID NO:72, the HC-CDR2 comprises SEQ ID NO:74, the HC-CDR3 comprises SEQ ID NO:76, the LC-CDR1 comprises SEQ ID NO:263, the 2 comprises SEQ ID NO:155 and the LC-CDR3 comprises SEQ ID NO:157.
4. The ed dy or antigen-binding fragment thereof of Claim 1, wherein the HCCDR1 comprises SEQ ID NO:79, the HC-CDR2 comprises SEQ ID NO:74, the HC-CDR3 comprises SEQ ID NO:82, the LC-CDR1 comprises SEQ ID NO:159, the LC-CDR2 comprises SEQ ID NO:155 and the LC-CDR3 comprises SEQ ID NO:160.
5. The isolated antibody or antigen-binding fragment f of claim 1, wherein the heavy chain variable region comprises an amino acid sequence selected from the group ting of SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:251 and SEQ ID NO:252.
6. The isolated antibody or antigen-binding fragment thereof of claim 1, wherein the light chain variable region comprises an amino acid sequence selected from the group consisting of SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:253 and SEQ ID NO:279.
7. The dy or antigen binding fragment f of any one of Claims 1-6, wherein the antibody or antigen-binding fragment is ed from the group consisting of a human antibody, a humanized antibody, a chimeric antibody, a murine antibody, and an antigen-binding fragment of any of the foregoing.
8. The antibody or antigen-binding fragment thereof of any one of Claims 1-7, wherein said antibody or antigen g fragment 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 dy.
9. The antibody or antigen-binding fragment thereof of any one of Claims 1-8, wherein said antibody inhibits alternative pathway activation in mammalian blood.
10. An isolated antibody or antigen-binding fragment thereof that binds to human MASP-3, comprising a) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:28 and a light chain variable region sing an amino acid sequence set forth in SEQ ID NO:43; b) a heavy chain variable region sing an amino acid ce as set forth in SEQ ID NO:251 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:253; c) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:252 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:253; d) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:251 and a light chain variable region sing an amino acid sequence set forth in SEQ ID NO:279; e) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:252 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:279; or f) a heavy chain variable region comprising an amino acid sequence as set forth in SEQ ID NO:29 and a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO:44.
11. The isolated antibody or antigen-binding nt thereof of claim 10, wherein the heavy chain variable region comprises SEQ ID NO:28 and the light chain variable region comprises SEQ ID NO:43.
12. The isolated antibody or antigen-binding fragment thereof of claim 10, wherein the heavy chain variable region comprises SEQ ID NO:29 and the light chain le region comprises SEQ ID NO:44.
13. The ed antibody or antigen-binding fragment thereof of claim 10, wherein the heavy chain variable region comprises SEQ ID NO:251 or SEQ ID NO:252 and the light chain variable region comprises SEQ ID NO:253.
14. The ed antibody or antigen-binding nt thereof of claim 10, wherein the heavy chain variable region comprises SEQ ID NO:251 or SEQ ID NO:252 and the light chain variable region comprises SEQ ID NO:279.
15. The isolated antibody of any one of claims 10-14, wherein the antibody 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.
16. The isolated antibody or antigen-binding fragment thereof of any one of claims 10-15, wherein said dy inhibits ative pathway activation in mammalian blood.
17. A composition comprising the antibody or antigen-binding fragment of any one of claims 1-16 and a pharmaceutically acceptable excipient.
18. An isolated DNA sequence encoding the heavy and light chain variable regions of an antibody or antigen-binding fragment f from any one of claims 1-16.
19. A combination of an isolated DNA ce encoding the heavy chain variable region and an isolated DNA sequence ng the light chain variable region of the antibody or antibody-binding fragment thereof of any one of claims 1-16.
20. A cloning or expression vector comprising one or more DNA sequences of Claim 18 or a combination of two or more cloning or expression vectors that comprise the combination of DNA sequences of claim 19.
21. A host cell comprising one or more g or expression vectors of Claim 20, provided that if the cell is a human cell it is ex vivo.
22. A process for producing the antibody or n-binding fragment thereof of any one of claims 1-16 comprising culturing the host cell of clam 21 and isolating the antibody or antigen-binding fragment thereof.
23. Use of the antibody or antigen binding fragment f of any one of claims 1- 16 or the composition of claim 17 in the manufacture of a medicament for inhibiting alternative pathway complement tion.
24. Use of the antibody or antigen binding fragment thereof of any one of claims 1- 16 or the composition of claim 17 in the manufacture of a medicament for treating a subject suffering from, or at risk for ping a disease or disorder selected from the group consisting of amyotrophic lateral sclerosis (ALS), lupus nephritis, systemic lupus matosus, uveitis, chronic obstructive pulmonary disease (COPD), C3 glomerulopathy, ANCA vasculitis, IgA nephropathy, and myasthenia gravis.
25. The isolated antibody or antigen-binding fragment thereof of Claim 1, substantially as here described with reference to any one of the examples and/or
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