Hybrid antibodies

• US 7,393,648 B2
• Filed: 06/03/2003
• Issued: 07/01/2008
• Est. Priority Date: 12/03/2001
• Status: Active Grant

• Current Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Original Assignee: Alexion Pharmaceuticals Incorporated (Astrazeneca PLC)
• Inventors: Wu, Dayang, Rother, Russell
• Primary Examiner(s): Helms; Larry
• Assistant Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US10/453,698
• Publication Number:
  US 20040038308A1
• Time in Patent Office: 1,855 Days
• Field of Search: 435/7.1, 530/387.3, 536/23.53
• US Class Current: 435/7.1
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2851 against the lectin superfamily, e.g. CD23, CD72
• CPC Class Codes: C07K 16/464 Igs containing CDR-residues from one specie grafted between FR-residues from another
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/567 Framework region [FR]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Hybrid antibodies and/or hybrid antibody fragments and methods of making them are provided. In one embodiment the hybrid antibodies and/or hybrid antibody fragments contain heavy and/or light variable regions that contain two or more framework regions derived from at least two antibodies. In another embodiment, at least two of the framework regions are classified in the same germline gene family. In one embodiment, at least two framework regions are classified in the same germline gene family member. The hybrid antibodies or hybrid antibody fragments may contain human framework regions and nonhuman CDRs.

Claims

1. A hybrid antibody or hybrid antibody fragment comprising

(a) complementarity determining regions (CDRs) of an initial antibody, wherein said initial antibody is specific for a target,

(b) a first heavy chain framework region from a first antibody, the first heavy chain framework region corresponding to a particular VH germline gene family, and

(c) a second heavy chain framework region from a second antibody, the second heavy chain framework region corresponding to the same VH germline gene family as the first heavy chain framework region,

wherein the first and second heavy chain framework regions are selected from the group consisting of FR1, FR2 and FR3, and wherein the hybrid antibody or hybrid antibody fragment is specific for said target.

2. A hybrid antibody or hybrid antibody fragment according to claim 1 further comprising a third heavy chain framework region from an antibody selected from the group consisting of the first antibody, the second antibody and a third antibody which is neither the first nor the second antibody, the third heavy chain framework region corresponding to the same VH germline gene family as the first heavy chain framework region, wherein the third heavy chain framework region is selected from the group consisting of FR1, FR2 and FR3.

3. A hybrid antibody or hybrid antibody fragment according to claim 2 further comprising an FR4 heavy chain framework region from an antibody selected from the group consisting of the first antibody, the second antibody, the third antibody and a fourth antibody which is neither the first, the second nor the third antibody.

4. A hybrid antibody or hybrid antibody fragment according to claim 3 wherein either, or both, of the second heavy chain framework region and the third heavy chain framework region correspond to the same member of the VH germline gene family as the first heavy chain framework region.

5. A hybrid antibody or hybrid antibody fragment according to claim 1 wherein the framework regions are of human origin and the CDRs are of nonhuman origin.

6. A hybrid antibody or hybrid antibody fragment comprising

(a) CDRs of an initial antibody, wherein said initial antibody is specific for a target,

(b) a first light chain framework region from a first antibody, the first light chain framework region corresponding to a particular VK germline gene family, and

(c) a second light chain framework region from a second antibody, the second light chain framework region corresponding to the same VK germline gene family as the first light chain framework region,

wherein the first and second light chain framework regions are selected from the group consisting of FR1, FR2 and FR3, and wherein the hybrid antibody or hybrid antibody fragment is specific for said target.

7. A hybrid antibody or hybrid antibody fragment according to claim 6 further comprising a third light chain framework region from an antibody selected from the group consisting of the first antibody, the second antibody and a third antibody which is neither the first nor the second antibody, the third light chain framework region corresponding to the same VK germline gene family as the first light chain framework region, wherein the third light chain framework region is selected from the group consisting of FR1, FR2 and FR3.

8. A hybrid antibody or hybrid antibody fragment according to claim 7 further comprising an FR4 light chain framework region from an antibody selected from the group consisting of the first antibody, the second antibody, the third antibody and a fourth antibody which is neither the first, the second nor the third antibody.

9. A hybrid antibody or hybrid antibody fragment according to claim 8 wherein either, or both, of the second light chain framework region and the third light chain framework region correspond to the same member of the VK germline gene family as the first light chain framework region.

10. A hybrid antibody or hybrid antibody fragment according to claim 6 wherein the framework regions are of human origin and the CDRs are of nonhuman origin.

11. A hybrid antibody or hybrid antibody fragment comprising

(a) CDRs of an initial antibody, wherein said initial antibody is specific for a target,

(b) a first light chain framework region from a first antibody, the first light chain framework region corresponding to a particular VL germline gene family, and

(c) a second light chain framework region from a second antibody, the second light chain framework region corresponding to the same VL germline gene family as the first light chain framework region,

wherein the first and second light chain framework regions are selected from the group consisting of FR1, FR2 and FR3, and wherein the hybrid antibody or hybrid antibody fragment is specific for said target.

12. A hybrid antibody or hybrid antibody fragment according to claim 11 further comprising a third light chain framework region from an antibody selected from the group consisting of the first antibody, the second antibody and a third antibody which is neither the first nor the second antibody, the third light chain framework region corresponding to the same VL germline gene family as the first light chain framework region, wherein the third light chain framework region is selected from the group consisting of FR1, FR2 and FR3.

13. A hybrid antibody or hybrid antibody fragment according to claim 12 further comprising an FR4 light chain framework region from an antibody selected from the group consisting of the first antibody, the second antibody, the third antibody and a fourth antibody which is neither the first, the second nor the third antibody.

14. A hybrid antibody or hybrid antibody fragment according to claim 13 wherein either, or both, of the second light chain framework region and the third light chain framework region correspond to the same member of the VL germline gene family as the first light chain framework region.

15. A hybrid antibody or hybrid antibody fragment according to claim 11 wherein the framework regions are of human origin and the CDRs are of nonhuman origin.