Dual targeting

• US 9,944,719 B2
• Filed: 12/05/2013
• Issued: 04/17/2018
• Est. Priority Date: 12/05/2012
• Status: Active Grant

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Beckmann, Roland, Jensen, Kristian
• Primary Examiner(s): Boesen, Christian C
• Application Number:
  US14/650,083
• Publication Number:
  US 20150315295A1
• Time in Patent Office: 1,594 Days
• Field of Search: None
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 16/243 Colony Stimulating Factors
• CPC Class Codes: C07K 16/248 IL-6
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C12N 15/1037 Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof

Abstract

The present invention relates to antibody-based dual targeting molecules, and to methods for generating such dual targeting molecules, including a library-based approach.

Claims

1. Rewrite as “

A collection of antibodies or functional fragments thereof, wherein said collection comprises a diverse collection of antibody variable domain sequences wherein said antibody variable domain sequences comprise a combination of a VL domain and a VH domain,

(A)

a. wherein said VL domain is based on a framework selected from SEQ-ID NOs;

1, 3, 5, and 7, wherein said VL domain is diversified in accordance with the diversification scheme shown in any one of SEQ-ID NOs;

8, 12, 18 or 19; and

b. wherein said VH domain is based on a framework selected from SEQ-ID NOs;

2, 4 and 6, wherein said VH domain is diversified in accordance with the diversification scheme shown in any one of SEQ-ID NOs;

9, 13, 20 or 21;

c. provided that a combination of a VL domain based on SEQ-ID NO;

1, which is diversified in accordance with the diversification scheme shown in SEQ-ID NOs;

18 or 19, and a VH domain based on SEQ-ID NO;

2, which is diversified in accordance with the diversification scheme shown in SEQ-ID NOs;

20 or 21 is excluded;

or

(B)

a. wherein said VL domain is based on a framework selected from SEQ-ID NOs;

1, 3, 5, and 7, wherein said VL domain is diversified in accordance with the diversification scheme shown in any one of SEQ-ID NOs;

10, 14, 16, 22 or 23; and

b. wherein said VH domain is based on a framework selected from SEQ-ID NOs;

2, 4 and 6, wherein said VH domain is diversified in accordance with the diversification scheme shown in any one of SEQ-ID NOs;

11, 15, 17, 24, 25 or 26;

c. provided that a combination of a VL domain based on SEQ-ID NO;

1, which is diversified in accordance with the diversification scheme shown in SEQ-ID NOs;

22 or 23, and a VH domain based on SEQ-ID NO;

2, which is diversified in accordance with the diversification scheme shown in SEQ-ID NOs;

24, 25 or 26 is excluded.”

2. A method for producing the collection of antibodies or functional fragments thereof according to claim 1, comprising the step of (i) expressing a collection of nucleic acid sequences encoding the collection of antibodies or functional fragments thereof according to claim 1, (ii) expressing a collection of nucleic acid sequences from a collection of vectors, particularly expression vectors, comprising a collection of nucleid acid sequences encoding the collection of antibodies or functional fragments thereof according to claim 1, and/or (iii) cultivating a collection of host cells comprising a collection of nucleic acid sequences encoding the collection of antibodies or functional fragments thereof according to claim 1, under conditions that cause or allow the expression of the nucleic acid sequences.

3. A method for identifying an antibody or functional fragment thereof with binding specificity for a target of interest, comprising the steps of contacting the collection of antibodies or functional fragments thereof according to claim 1 with the target of interest and screening or selecting for antibodies or functional fragments thereof with binding specificity for said target of interest.

4. The method of claim 3, wherein said screening or selecting is using phage display.