Compositions and methods for treatment and detection of cancers

• US 9,982,041 B2
• Filed: 01/16/2015
• Issued: 05/29/2018
• Est. Priority Date: 01/16/2014
• Status: Active Grant

• Current Assignee: Academia Sinica (Government of The Republic of China)
• Original Assignee: Academia Sinica (Government of The Republic of China)
• Inventors: Wong, Chi-Huey, Hsu, Tsui-Ling, Lou, Yi-Wei, Lin, Chih-Wei, Yeh, Shih-Chi, Wu, Chung-Yi, Wu, Han-Chung
• Primary Examiner(s): BRISTOL, LYNN ANNE
• Application Number:
  US14/599,174
• Publication Number:
  US 20150344551A1
• Time in Patent Office: 1,229 Days
• Field of Search: 4241331, 4241371, 5303873, 5303875
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/3053 Skin, nerves, brain
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/54 F(ab')2
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells

Abstract

Pharmaceutical composition comprising antibodies or antigen binding fragments thereof that bind to SSEA-4 are disclosed herein, as well as methods of use thereof. Methods of use include, without limitation, cancer therapies and diagnostics. The antibodies of the disclosure can bind to certain cancer cell surfaces. Exemplary targets of the antibodies disclosed herein can include carcinomas, such as those in brain, lung, breast, mouse, esophagus, stomach, liver, bile duct, pancreas, colon, kidney, cervix, ovary, and/or prostate cancer.

Claims

1. An isolated monoclonal antibody that specifically binds to Neu5Acα

2→

3Galβ

1→

3GalNAcβ

1→

3Galα

1→

4Galβ

1→

4Glcβ

1, wherein the antibody comprises an H-CDR1, H-CDR2, and H-CDR3 wherein;

(i) the H-CDR1 has the sequence of SEQ ID NO;

80;

(ii) the H-CDR2 has the sequence of SEQ ID NO;

82; and

(iii) the H-CDR3 has the sequence SEQ ID NO;

90, respectively;

and comprises an L-CDR1, L-CDR2 and L-CDR3 wherein;

(iv) the L-CDR1 has the sequence of SEQ ID NO;

99;

(v) the L-CDR2 has the sequence of SEQ ID NO;

101; and

(vi) the L-CDR3 has the sequence of SEQ ID NO;

109, respectively.

2. The isolated monoclonal antibody of claim 1, which further binds to Neu5Acα

2→

3Galβ

1→

3GalNAcβ

1→

3Galα

1.

3. The isolated monoclonal antibody of claim 1, wherein the antibody is an IgG1.

4. The isolated monoclonal antibody of claim 1, wherein the antibody is a humanized antibody, a chimeric antibody or a single-chain antibody.

5. The isolated monoclonal antibody of claim 1, wherein the antibody further comprises an H-FR1, H-FR2, H-FR3, and HFR4, wherein:

(i) the H-FR1 has the sequence of SEQ ID NO;

79, SEQ ID NO;

83, SEQ ID NO;

85 or SEQ ID NO;

87;

(ii) the H-FR2 has the sequence of SEQ ID NO;

81, SEQ ID NO;

84, SEQ ID NO;

86 or SEQ ID NO;

88;

(iii) the H-FR3 has the sequence of SEQ ID NO;

89, SEQ ID NO;

92, SEQ ID NO;

94 or SEQ ID NO;

96; and

(iv) the H-FR4 has the sequence of SEQ ID NO;

91, SEQ ID NO;

93, SEQ ID NO;

95 or SEQ ID NO;

97, respectively; and

wherein the antibody further comprises an L-FR1, L-FR2, L-FR3 and L-FR4 wherein;

(v) the L-FR1 has the sequence of SEQ ID NO;

98, SEQ ID NO;

102, SEQ ID NO;

104 or SEQ ID NO;

106;

(vi) the L-FR2 has the sequence of SEQ ID NO;

100, SEQ ID NO;

103, SEQ ID NO;

105 or SEQ ID NO;

107;

(vii) the L-FR3 has the sequence of SEQ ID NO;

108, SEQ ID NO;

111, SEQ ID NO;

113 or SEQ ID NO;

114; and

(viii) the L-FR4 selected from has the sequence of SEQ ID NO;

110 or SEQ ID NO;

112, respectively.

6. A pharmaceutical composition comprising the antibody or antigen binding fragment thereof according to claim 1.

7. An antigen-binding fragment of the isolated monoclonal antibody of claim 1.

8. The antigen-binding fragment of claim 7, wherein the antigen binding fragment is a Fab fragment, a F(ab′

)2 fragment, or a single-chain Fv fragment.