Human Binding Molecules Having Killing Activity Against Staphylococci and Uses Thereof

• US 20090104204A1
• Filed: 06/05/2007
• Published: 04/23/2009
• Est. Priority Date: 06/06/2006
• Status: Active Grant

• Current Assignee: Crucell Holland B.V (Johnson & Johnson)
• Original Assignee: Crucell Holland B.V (Johnson & Johnson)
• Inventors: Throsby, Mark, De Kruif, Cornelis Adriaan, Geuijen, Cecilia A.W.
• Granted Patent: US 8,211,431 B2
• Time in Patent Office: Days
• US Class Current: 424/142.100
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/1271 from Micrococcaceae (F), e.g. Staphylococcus
• 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 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/77 Internalization into the cell

Abstract

The present invention provides human binding molecules specifically binding to staphylococci and having killing activity against staphylococci, nucleic acid molecules encoding the human binding molecules, compositions comprising the human binding molecules and methods of identifying or producing the human binding molecules. The human binding molecules can be used in the diagnosis, prophylaxis and/or treatment of a condition resulting from Staphylococcus.

Claims

1. A human monoclonal antibody, characterized in that it has opsonic phagocytic killing activity against at least two different Staphylococcus species and against at least 3 different strains of Staphylococcus aureus, wherein the antibody is selected from the group consisting of:

i) an antibody with a heavy chain comprising the variable region of SEQ ID NO;

30 and a light chain comprising the variable region of SEQ ID NO;

36, or an antibody with variable regions that are at least 80% identical thereto;

ii) an antibody with a heavy chain comprising the variable region of SEQ ID NO;

117 and a light chain comprising the variable region of SEQ ID NO;

177, or an antibody with variable regions that are at least 80% identical thereto;

iii) an antibody with a heavy chain comprising the variable region of SEQ ID NO;

119 and a light chain comprising the variable region of SEQ ID NO;

179, or an antibody with variable regions that are at least 80% identical thereto;

iv) an antibody with a heavy chain comprising the variable region of SEQ ID NO;

121 and a light chain comprising the variable region of SEQ ID NO;

181, or an antibody with variable regions that are at least 80% identical thereto; and

v) an antibody with a heavy chain comprising the variable region of SEQ ID NO;

155 and a light chain comprising the variable region of SEQ ID NO;

215, or an antibody with variable regions that are at least 80% identical thereto.

2. The human monoclonal antibody according to claim 1, characterized in that it has said opsonic phagocytic killing activity when the Staphylococcus species are in logarithmic growth phase and in static phase.

3. The human monoclonal antibody according to claim 1, characterized in that the Staphylococcus species comprise S. aureus and S. epidermidis.

4. A composition comprising at least two human antibodies of claim 1.

5. An immunoconjugate comprising the human monoclonal antibody of claim 1, the immunoconjugate further comprising at least one tag.

6. A nucleic acid molecule encoding the human monoclonal antibody of claim 1.

7. A vector comprising at least one nucleic acid molecule according to claim 6.

8. A host cell comprising at least one vector according to claim 7.

9. A method of producing a human monoclonal antibody, wherein the method comprises:

a) culturing the host cell according to claim 8 under conditions conducive to the expression of the human monoclonal antibody.

10. A pharmaceutical composition comprising the human monoclonal antibody of claim 1, the pharmaceutical composition further comprising at least one pharmaceutically acceptable excipient.

11. The pharmaceutical composition according to claim 10 further comprising at least one other therapeutic agent.

12. A method of treating a staphylococcal infection, the method comprising:

utilizing a human monoclonal antibody according to claim 1 in the treatment of a staphylococcal infection.

13. The method according to claim 9, further comprising:

b) recovering the expressed human monoclonal antibody.

14. A method of diagnosing a staphylococcal infection, the method comprising:

utilizing the human monoclonal antibody of claim 1 in the diagnosis of a staphylococcal infection.

15. A method of preventing a staphylococcal infection, the method comprising:

utilizing the human monoclonal antibody of claim 1 in the prevention of a staphylococcal infection.

16. A method of diagnosing and treating a staphylococcal infection, the method comprising:

utilizing the human monoclonal antibody of claim 1 in the diagnosis and treatment of a staphylococcal infection.