US 9,803,022 B2Granted

Mesothelin domain-specific monoclonal antibodies and use thereof

AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services

InventorsMitchell Ho, Ira H. Pastan, Yen T. Phung, Yifan Zhang, Wei Gao, Raffit Hassan

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Abstract

Described herein is the use of rabbit hybridoma technology, along with a panel of truncated mesothelin domain fragments, to identify anti-mesothelin mAbs that bind specific regions of mesothelin. In one aspect of the present disclosure, the rabbit mAbs bind an epitope that is not part of Region I. In particular, the identified mAbs (YP187, YP223, YP218 and YP3) bind either Region II (391-486), Region III (487-581) or a native conformation of mesothelin with subnanomolar affinity. These antibodies do not compete for binding with the mesothelin-specific immunotoxin SS1P or mesothelin-specific antibody MORAb-009. In another aspect, disclosed is a high-affinity rabbit mAb that binds Region I of mesothelin (YP158). YP158 binds native mesothelin protein in cancer cells and tissues with high affinity and specificity.

Claims28

Dependent claims

An isolated monoclonal antibody that binds mesothelin, wherein:

(i) the variable heavy (VH) domain of the antibody comprises a complementarity determining region (CDR) 1, a CDR2 and a CDR3 from SEQ ID NO:
13;
and the variable light (VL) domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
15;
(ii) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
9;
and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
11;
(iii) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
17;
and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
19;
(iv) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
21, or comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
29;
and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
23;
or
(v) the VH domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
25;
and the VL domain of the antibody comprises a CDR1, a CDR2 and a CDR3 from SEQ ID NO:
27.

19 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/141,006Filed 28 Apr 2016 · continuation
Priority: 21 Aug 2012
Published: US 2016/0229919 A111 Aug 2016
Granted: 31 Oct 2017
Term ends: Not estimatedThe source records don’t support an estimate.

Classification34 codes

C07K 16/30
Against receptors, cell surface antigens or cell surface determinants: from tumour cells
A61K 39/395
Medicinal preparations containing antigens or antibodies: antibodies ; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61K 47/6829
Toxins: bacterial toxins, e.g. diphteria toxins or Pseudomonas exotoxin A
A61K 47/6849
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a receptor, a cell…

Family

Application61/691,719Us provisional application · filed 21 Aug 2012
PCT/US2013/055273Parent of this continuation · filed 16 Aug 2013
US 2016/0229919 A1Pre-grant publication · published 11 Aug 2016
Application14/421,599Parent of this continuation
US 9,409,992 B2Parent of this continuation
US 2015/0252118 A1Published application
US 9,803,022 B2This patent

From the US filing history. Foreign family members aren’t listed.