Optimized proteins that target Ep-CAM

• US 7,557,190 B2
• Filed: 07/10/2006
• Issued: 07/07/2009
• Est. Priority Date: 07/08/2005
• Status: Active Grant

• Current Assignee: Xencor, Inc.
• Original Assignee: Xencor, Inc.
• Inventors: Barbosa, Maria D., Desjarlais, John R., Chamberlain, Aaron K.
• Primary Examiner(s): Haddad; Maher M
• Assistant Examiner(s): DAHLE, CHUN WU
• Application Number:
  US11/484,183
• Publication Number:
  US 20070161783A1
• Time in Patent Office: 1,093 Days
• Field of Search: None
• US Class Current: 530/387.1
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/465 with additional modified FR-residues
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/72 Increased effector function due to an Fc-modification
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Humanized Ep-CAM-targeting antibodies and methods of making and using the same are provided.

Claims

1. A humanized variant anti-EpCAM antibody variable domain relative to antibody 17-1A variable domain, wherein said 17-1A variable domain comprises a heavy chain, SEQ ID NO:

1, and a light chain SEQ ID NO;

105, and,

wherein said variant comprises at least one modification selected from the group consisting of;

a first variant heavy chain framework region, a second variant heavy chain framework region, a third variant heavy chain framework region, a first variant light chain framework region, a

second variant light chain framework region, and a third variant light chain framework region,

wherein said first variant heavy chain framework region consists of Q5V and R13Q relative to SEQ ID NO;

1,

wherein said second variant heavy chain framework region consists of K38R, R40A and I48M relative to SEQ ID NO;

1,

wherein said third variant heavy chain framework region consists of K63S, F64L, G66S, K67R, A68V, L70I and T71S relative to SEQ ID NO;

1,

wherein said first variant light chain framework region consists of K9D, M11L, S12A, M13V and V15L relative to SEQ ID NO;

105,

wherein said second variant light chain framework region consists of E41G and K45Q relative to SEQ ID NO;

105, and,

wherein said third variant light chain framework region consists of S76N, V78L, Q79E, L83A, D85T and H87Y relative to SEQ ID NO;

105,

wherein said variant anti-EpCAM antibody variable domain contains an increased human string content relative to antibody 17-1A variable domain.

2. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said first variant heavy chain framework.

3. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said second variant heavy chain framework.

4. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said third variant heavy chain framework.

5. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said first variant light chain framework.

6. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said second variant light chain framework.

7. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said third variant light chain framework.

8. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said first variant heavy chain framework and said second variant heavy chain framework and said third variant heavy chain framework.

9. The humanized variant anti-EpCAM antibody variable domain of claim 1, where said at least one modification comprises said first variant light chain framework and said second variant light chain framework and said third variant light chain framework.

10. The humanized variant anti-EpCAM antibody variable domain of claim 9, where said at least one modification further comprises said first variant heavy chain framework and said second variant heavy chain framework and said third variant heavy chain framework.