# US 2010/0166748 A1 · C5 Antigens and Uses Thereof

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- Number: US 2010/0166748 A1
- Document ID: US20100166748A1
- Status: Published application
- Kind: A1
- Application number: 12/532,261
- Filed: 2008-03-19
- Published: 2010-07-01
- Earliest claimed: 2007-03-22
- Assignees: Novartis AG
- Inventors: Braydon Charles Guild; Mark Taylor Keating; Mariusz Milik; Dmitri Mikhailov; Michael Roguska; Igor Splawski; Kehao Zhao
- Web page: https://patentgrep.com/patent/US20100166748A1

## CPC

- G01N 33/6893: {related to diseases not provided for elsewhere}
- A61P 27/02: Ophthalmic agents
- A61P 27/04: Artificial tears; Irrigation solutions
- G01N 2333/4716: Complement proteins, e.g. anaphylatoxin, C3a, C5a
- G01N 2800/16: Ophthalmology
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention pertains to the use of a complement inhibitor in methods of treatment of ocular disorders and the use of a complement inhibitor in the manufacture of a medicament in the treatment of an ocular disorder.

## Claims

### Claim 1

An isolated polynucleotide having at least 95% nucleic acid sequence identity to a nucleic acid sequence selected from the group consisting of SEQ ID Nos. 2, 4, and 6.

### Claim 2

An isolated polynucleotide comprising a nucleic acid sequence selected from the group consisting of SEQ ID Nos. 2, 4, and 6.

### Claim 3 (depends on 2)

A vector comprising the polynucleotide of claim 2 operably linked to a control sequence.

### Claim 4 (depends on 3)

A host cell comprising the vector of claim 3.

### Claim 5

An isolated polypeptide having at least 95% amino acid identity to an amino acid sequence selected from the group consisting SEQ ID Nos 1, 3 and 5.

### Claim 6

An isolated polypeptide comprising an amino acid sequence selected from the group consisting SEQ ID Nos 1, 3 and 5.

### Claim 7 (depends on 4)

A method for producing a C5 protein, said method comprising culturing the host cell of claim 4 under conditions suitable for expression of said polypeptide and recovering said polypeptide from the cell culture.

### Claim 8 (depends on 7)

The method of claim 7 wherein said C5 proteins comprise epitopes selected from the group consisting of SEQ ID No. 1, 3 and 5.

### Claim 9

An isolated C5 binding molecule comprising an antigen binding portion of an antibody that specifically binds to a C5 epitope within or overlapping amino acids selected from the group consisting of SEQ ID Nos 1, 3 and 5.

### Claim 10 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion is cross reactive with a C5 antigen of a non-human primate.

### Claim 11 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion is cross reactive with a C5 antigen of a rodent species.

### Claim 12 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion binds to a linear epitope.

### Claim 13 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion binds to a non-linear epitope.

### Claim 14 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion binds to a human C5 antigen with a KD equal to or less than 0.1 nM.

### Claim 15 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion binds to C5 antigen of a non-human primate with a KD equal to or less than 0.3 nM.

### Claim 16 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion thereof binds to mouse C5 antigen with a KD equal to or less than 0.5 nM.

### Claim 17

The C5 binding molecule of any preceding claim, wherein the antigen binding portion is an antigen binding portion of a human antibody.

### Claim 18 (depends on 9)

The C5 binding molecule of claim 9, wherein the antibody is a humanized antibody.

### Claim 19 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion is an antigen binding portion of a monoclonal antibody.

### Claim 20 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion is an antigen binding portion of a polyclonal antibody.

### Claim 21 (depends on 9)

The C5 binding molecule of claim 9, wherein the C5 binding molecule is a chimeric antibody.

### Claim 22 (depends on 9)

The C5 binding molecule of claim 9, wherein the C5 binding molecule comprises an Fab fragment, an Fab′ fragment, an F(ab′)2, or an Fv fragment of the antibody.

### Claim 23 (depends on 9)

The C5 binding molecule of claim 9, wherein the C5 binding molecule comprises a single chain Fv.

### Claim 24 (depends on 9)

The C5 binding molecule of claim 9, wherein the C5 binding molecule comprises a diabody.

### Claim 25 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion is derived from an antibody of one of the following isotypes: IgG1, IgG2, IgG3 or IgG4.

### Claim 26 (depends on 9)

The C5 binding molecule of claim 9, wherein the antigen binding portion is derived from an antibody of one of the following isotypes: IgG1, IgG2, IgG3 or IgG4 in which the Fc sequence has been altered relative to the normal sequence in order to modulate effector functions or alter binding to Fc receptors.

### Claim 27 (depends on 9)

The C5 binding molecule of claim 9, wherein the C5 binding molecule inhibit MAC production in a cell.

### Claim 28 (depends on 9)

The C5 binding molecule of claim 9, wherein the C5 binding molecule inhibits C5 binding to a convertase.

### Claim 29

A method of inhibiting MAC synthesis in a cell, the method comprising contacting a cell with a C5 binding molecule.

### Claim 30

A method of modulating MAC activity in a subject, the method comprising administering to the subject a C5 binding molecule that modulates cellular activities mediated by the complement system.

### Claim 31

A method of treating or preventing an ocular disorder in a subject, the method comprising administering to the subject an effective amount of a binding molecule which specifically binds to an epitope selected from SEQ ID Nos. 1, 3 and 5.

### Claim 32 (depends on 31)

The method of claim 31, wherein the subject's level of MAC is reduced by at least 5%, relative to the level of MAC in a subject prior to administering the binding molecule.

### Claim 33 (depends on 31)

The method of claim 31 wherein the binding molecule is administered intravitreally.

### Claim 34 (depends on 31)

The method of claim 31 wherein said ocular disorder is selected from the group consisting of macular degeneration, diabetic ocular diseases and disorders, ocular edema, ischemic retinopathy, anterior ischemic optic neuropathy, optic neuritis, cystoid macular edema, retinal diseases and disorders, pathologic myopia, retinopathy of prematurity, vascularized, rejecting, or otherwise inflamed corneas, keratoconjunctivitis sicca, dry eye, uveitis, scleritis, episcleritis, conjunctivitis, keratitis, orbital cellulitis, ocular myositis, thyroid orbitopathy, lacrimal gland and eyelid inflammation.

### Claim 35 (depends on 31)

The method of claim 31 wherein said binding molecule is a monoclonal antibody.

### Claim at position 36

-40. (canceled)

### Claim 41 (depends on 9)

A kit for detecting the presence of C5 proteins comprising a container containing the antibody of claim 9 and instructions for detecting said proteins bound by said antibody.

### Claim 42 (depends on 41)

The kit of claim 41 wherein the antibody further comprises a detectable label.

### Claim 43

A method of treating or inhibiting an ocular disease or disorder, or delaying their progression; the method comprising administering an effective amount of a protein capable of inhibiting the alternate complement pathway to a subject in need of such treatment.
