Stabilized Angiopoietin-2 Antibodies And Uses Thereof

• US 20110044998A1
• Filed: 01/28/2009
• Published: 02/24/2011
• Est. Priority Date: 01/28/2008
• Status: Active Grant

• Current Assignee: MedImmune Ltd. (Astrazeneca PLC)
• Original Assignee: MedImmune Ltd. (Astrazeneca PLC)
• Inventors: Bowden, Michael, Wu, Herren, Brown, Jeffrey, Stannard, Chris, Bedian, Vahe, Dall'Acqua, William
• Granted Patent: US 8,507,656 B2
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/282 Platinum compounds
• CPC Class Codes: A61K 31/337 having four-membered rings, e.g. taxol
• CPC Class Codes: A61K 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/513 having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 38/1793 for cytokines; for lymphokines; for interferons
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 33/00 : Antiparasitic agents
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/22 : against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/21 : from primates, e.g. man
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/73 : Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

Stabilized antibodies directed to Angiopoeitin-2 and uses of such antibodies are described. Nucleic acid and amino acid sequences, hybridomas or other cell lines for expressing such antibodies are also provided.

Claims

1-85. -85. (canceled)

86. An isolated antibody that binds to angiopoietin-2 (Ang-2), wherein the antibody comprises a light chain variable region of;

a) SEQ ID No;

3 (MEDI1);

b) SEQ ID No;

4 (MEDI2);

c) SEQ ID No;

5 (MEDI3);

d) SEQ ID No;

6 (MEDI4);

or

e) SEQ ID No;

8 (MEDI6).

87. The antibody according to claim 86, wherein the antibody comprises a light chain variable region of SEQ ID No:

3 (MEDI1).

88. The antibody according to claim 86, wherein the antibody, when produced, exhibits a production efficiency in a mammalian host cell equal to or greater than 2 times the production efficiency of an Ang-2 antibody comprising SEQ ID No:

1 and SEQ ID No;

2 (3.19.3).

89. The antibody according to claim 86, wherein exhibits an aggregation rate that is at least 10% lower than the aggregation rate of an Ang-2 antibody comprising SEQ ID No:

1 and SEQ ID No;

2 (3.19.3).

90. The antibody according to claim 86, wherein exhibits a melting temperature that is higher than the melting temperature of an Ang-2 antibody comprising SEQ ID No:

1 and SEQ ID No;

2 (3.19.3).

91. The antibody according to claim 86, wherein the antibody further comprises a heavy chain variable region of SEQ ID No:

7 (MEDI5).

92. The antibody according to claim 86, wherein the antibody comprises a light chain variable region of SEQ ID No:

3 (MEDI1) and a heavy chain variable region of SEQ ID No;

7 (MEDI5).

93. An isolated nucleic acid encoding at least one isolated antibody that binds to Ang-2 comprising a heavy and light chain variable region of SEQ ID No:

3 (MEDI1) and SEQ ID No;

7 (MEDI5).

94. A pharmaceutical composition comprising:

a) an isolated antibody that binds to Ang-2, wherein the antibody comprises a light chain variable region of SEQ ID No;

3 (MEDI1) and a heavy chain variable region of SEQ ID No;

7 (MEDI5); and

,

b) an excipient.

95. A method of inhibiting angiogenesis of a cancer tumor in an animal in need thereof, wherein the method comprises administering to the animal a composition comprising;

a) an isolated antibody that binds to Ang-2, wherein the antibody comprises a light chain variable region of SEQ ID No;

3 (MEDI1) and a heavy chain variable region of SEQ ID No;

7 (MEDI5); and

,

b) an excipient.

96. The method according to claim 95, wherein the composition further comprises one or more other cancer therapeutic agents.

97. The method according to claim 95, wherein the cancer is selected from the group consisting of melanoma, colon, colorectal, lung, small cell lung carcinoma, non-small cell lung carcinoma, breast, rectum, stomach, glioma, prostate, ovary, testes, thyroid, kidney, liver, hepatocellular carcinoma pancreas, brain, neck, glioblastoma, endometrial cancer, and central nervous system cancer.

98. The method according to claim 95, wherein the composition is administered intravenously, subcutaneously, intratumorally, intramuscularly, parenterally, or orally.

99. A method of preventing, treating, or managing disease-related angiogenesis in an animal in need thereof, wherein the method comprises administering a composition comprising;

a) an isolated antibody that binds to Ang-2; and

,

b) an excipient.

100. The method according to claim 99, wherein the disease-related angiogenesis is associated with seronegative arthritis, seropositive arthritis, arthritis related to other arthropathies, osteoarthritis or SLE.

101. The method according to claim 100, wherein the seropositive arthritis is rheumatoid arthritis.

102. The method according to claim 99, wherein the method further comprises administering one or more anti-inflammatory therapeutic agents.

103. The method according to claim 102, wherein the anti-inflammatory therapeutic agent is a TNF-α

antagonist.

104. The method according to claim 99, wherein the antibody comprises a light chain variable region of SEQ ID No:

3 (MEDI1) and a heavy chain variable region of SEQ ID No;

7 (MEDI5).