US 2025/0051443 A1 · ANTI-CD3 MONOCLONAL ANTIBODIES AND THERAPEUTIC CONSTRUCTS

Abstract

Here is disclosed isolated or purified monoclonal antibodies, or an antigen-binding fragments thereof, which binds to human CD3, and which comprises: a CDRH1 amino acid sequence of SEQ ID NO: 150, a CDRH2 amino acid sequence of SEQ ID NO: 151, a CDRH3 amino acid sequence of SEQ ID NO: 152, a CDRL1 amino acid sequence of SEQ ID NO: 153, a CDRL2 amino acid sequence of SEQ ID NO: 154, and a CDRL3 amino acid sequence of SEQ ID NO: 155. Also provided are recombinant polypeptides comprising said monoclonal antibody, or an antigen-binding fragment thereof, such as multivalent antibodies, including bispecific T-cell engagers. Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the monoclonal antibodies, or antigen-binding fragments thereof. Nucleic acids encoding the aforementioned antibodies, fragments, and polypeptides are also disclosed, along with therapeutic applications in the treatment of and autoinflammatory disease or cancer.

Claims75

Dependent claims

An isolated or purified monoclonal antibody, or an antigen-binding fragment thereof, which binds to human CD3, and which comprises:

a CDRH1 amino acid sequence of SEQ ID NO:
150,
a CDRH2 amino acid sequence of SEQ ID NO:
151,
a CDRH3 amino acid sequence of SEQ ID NO:
152,
a CDRL1 amino acid sequence of SEQ ID NO:
153,
a CDRL2 amino acid sequence of SEQ ID NO:
154, and
a CDRL3 amino acid sequence of SEQ ID NO:
155.

9 more elements

An isolated or purified monoclonal antibody, or an antigen-binding fragment thereof, which binds to human CD3, and which comprises:

a CDRH1 amino acid sequence selected from the group consisting of SEQ ID NOs:
48, 54, 60, 66, 72, 78, 84, 90, 96, 102, 108, 114, 120, 126, 132, 138, and 144,
a CDRH2 amino acid sequence selected from the group consisting of SEQ ID NOs:
49, 55, 61, 67, 73, 79, 85, 91, 97, 103, 109, 115, 121, 127, 133, 139, and 145,
a CDRH3 amino acid sequence selected from the group consisting of SEQ ID NOs:
50, 56, 62, 68, 74, 80, 86, 92, 98, 104, 110, 116, 122, 128, 134, 140, and 146,
a CDRL1 amino acid sequence selected from the group consisting of SEQ ID NOs:
51, 57, 63, 69, 75, 81, 87, 93, 99, 105, 111, 117, 123, 129, 135, 141, and 147,
a CDRL2 amino acid sequence selected from the group consisting of SEQ ID NOs:
52, 58, 64, 70, 76, 82, 88, 94, 100, 106, 112, 118, 124, 130, 136, 142, and 148, and
a CDRL3 amino acid sequence selected from the group consisting of SEQ ID NOs:
53, 59, 65, 71, 77, 83, 89, 95, 101, 106, 113, 119, 125, 130, 136, 143, and 149.

9 more elements

An isolated or purified monoclonal antibody, or an antigen-binding fragment thereof, which binds to human CD3, and which comprises:

A)
i) a CDRH1 amino acid sequence of SEQ ID NO:
48,
a CDRH2 amino acid sequence of SEQ ID NO:
49,
a CDRH3 amino acid sequence of SEQ ID NO:
50,
a CDRL1 amino acid sequence of SEQ ID NO:
51,
a CDRL2 amino acid sequence of SEQ ID NO:
52, and
a CDRL3 amino acid sequence of SEQ ID NO:
53;
ii) a CDRH1 amino acid sequence of SEQ ID NO:
54,
a CDRH2 amino acid sequence of SEQ ID NO:
55,
a CDRH3 amino acid sequence of SEQ ID NO:
56,
a CDRL1 amino acid sequence of SEQ ID NO:
57,
a CDRL2 amino acid sequence of SEQ ID NO:
58, and
a CDRL3 amino acid sequence of SEQ ID NO:
59;
iii) a CDRH1 amino acid sequence of SEQ ID NO:
60,
a CDRH2 amino acid sequence of SEQ ID NO:
61,
a CDRH3 amino acid sequence of SEQ ID NO:
62,
a CDRL1 amino acid sequence of SEQ ID NO:
63,
a CDRL2 amino acid sequence of SEQ ID NO:
64, and
a CDRL3 amino acid sequence of SEQ ID NO:
65;
iv) a CDRH1 amino acid sequence of SEQ ID NO:
66,
a CDRH2 amino acid sequence of SEQ ID NO:
67,
a CDRH3 amino acid sequence of SEQ ID NO:
68,
a CDRL1 amino acid sequence of SEQ ID NO:
69,
a CDRL2 amino acid sequence of SEQ ID NO:
70, and
a CDRL3 amino acid sequence of SEQ ID NO:
71;
v) a CDRH1 amino acid sequence of SEQ ID NO:
72,
a CDRH2 amino acid sequence of SEQ ID NO:
73,
a CDRH3 amino acid sequence of SEQ ID NO:
74,
a CDRL1 amino acid sequence of SEQ ID NO:
75,
a CDRL2 amino acid sequence of SEQ ID NO:
76, and
a CDRL3 amino acid sequence of SEQ ID NO:
77;
vi) a CDRH1 amino acid sequence of SEQ ID NO:
78,
a CDRH2 amino acid sequence of SEQ ID NO:
79,
a CDRH3 amino acid sequence of SEQ ID NO:
80,
a CDRL1 amino acid sequence of SEQ ID NO:
81,
a CDRL2 amino acid sequence of SEQ ID NO:
82, and
a CDRL3 amino acid sequence of SEQ ID NO:
83;
vii) a CDRH1 amino acid sequence of SEQ ID NO:
84,
a CDRH2 amino acid sequence of SEQ ID NO:
85,
a CDRH3 amino acid sequence of SEQ ID NO:
86,
a CDRL1 amino acid sequence of SEQ ID NO:
87,
a CDRL2 amino acid sequence of SEQ ID NO:
88, and
a CDRL3 amino acid sequence of SEQ ID NO:
89;
viii) a CDRH1 amino acid sequence of SEQ ID NO:
90,
a CDRH2 amino acid sequence of SEQ ID NO:
91,
a CDRH3 amino acid sequence of SEQ ID NO:
92,
a CDRL1 amino acid sequence of SEQ ID NO:
93,
a CDRL2 amino acid sequence of SEQ ID NO:
94, and
a CDRL3 amino acid sequence of SEQ ID NO:
95;
ix) a CDRH1 amino acid sequence of SEQ ID NO:
96,
a CDRH2 amino acid sequence of SEQ ID NO:
97,
a CDRH3 amino acid sequence of SEQ ID NO:
98,
a CDRL1 amino acid sequence of SEQ ID NO:
99,
a CDRL2 amino acid sequence of SEQ ID NO:
100, and
a CDRL3 amino acid sequence of SEQ ID NO:
101;
x) a CDRH1 amino acid sequence of SEQ ID NO:
102,
a CDRH2 amino acid sequence of SEQ ID NO:
103,
a CDRH3 amino acid sequence of SEQ ID NO:
104,
a CDRL1 amino acid sequence of SEQ ID NO:
105,
a CDRL2 amino acid sequence of SEQ ID NO:
106, and
a CDRL3 amino acid sequence of SEQ ID NO:
107;
xi) a CDRH1 amino acid sequence of SEQ ID NO:
108,
a CDRH2 amino acid sequence of SEQ ID NO:
109,
a CDRH3 amino acid sequence of SEQ ID NO:
110,
a CDRL1 amino acid sequence of SEQ ID NO:
111,
a CDRL2 amino acid sequence of SEQ ID NO:
112, and
a CDRL3 amino acid sequence of SEQ ID NO:
113;
xii) a CDRH1 amino acid sequence of SEQ ID NO:
114,
a CDRH2 amino acid sequence of SEQ ID NO:
115,
a CDRH3 amino acid sequence of SEQ ID NO:
116,
a CDRL1 amino acid sequence of SEQ ID NO:
117,
a CDRL2 amino acid sequence of SEQ ID NO:
118, and
a CDRL3 amino acid sequence of SEQ ID NO:
119;
xiii) a CDRH1 amino acid sequence of SEQ ID NO:
120,
a CDRH2 amino acid sequence of SEQ ID NO:
121,
a CDRH3 amino acid sequence of SEQ ID NO:
122,
a CDRL1 amino acid sequence of SEQ ID NO:
123,
a CDRL2 amino acid sequence of SEQ ID NO:
124, and
a CDRL3 amino acid sequence of SEQ ID NO:
125;
xiv) a CDRH1 amino acid sequence of SEQ ID NO:
126,
a CDRH2 amino acid sequence of SEQ ID NO:
127,
a CDRH3 amino acid sequence of SEQ ID NO:
128,
a CDRL1 amino acid sequence of SEQ ID NO:
129,
a CDRL2 amino acid sequence of SEQ ID NO:
130, and
a CDRL3 amino acid sequence of SEQ ID NO:
131;
xv) a CDRH1 amino acid sequence of SEQ ID NO:
132,
a CDRH2 amino acid sequence of SEQ ID NO:
133,
a CDRH3 amino acid sequence of SEQ ID NO:
134,
a CDRL1 amino acid sequence of SEQ ID NO:
135,
a CDRL2 amino acid sequence of SEQ ID NO:
136, and
a CDRL3 amino acid sequence of SEQ ID NO:
137;
xvi) a CDRH1 amino acid sequence of SEQ ID NO:
138,
a CDRH2 amino acid sequence of SEQ ID NO:
139,
a CDRH3 amino acid sequence of SEQ ID NO:
140,
a CDRL1 amino acid sequence of SEQ ID NO:
141,
a CDRL2 amino acid sequence of SEQ ID NO:
142, and
a CDRL3 amino acid sequence of SEQ ID NO:
143;
or
xvii) a CDRH1 amino acid sequence of SEQ ID NO:
144,
a CDRH2 amino acid sequence of SEQ ID NO:
145,
a CDRH3 amino acid sequence of SEQ ID NO:
146,
a CDRL1 amino acid sequence of SEQ ID NO:
147,
a CDRL2 amino acid sequence of SEQ ID NO:
148, and
a CDRL3 amino acid sequence of SEQ ID NO:
149;
OR
B)
CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 amino acid sequences that are at least 80% identical to the CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3 sequences, respectively, defined in any one of A) i) to xvii).

206 more elements

Dependencies are inferred from the claim text.

Facts

Application

18/699,059Filed 5 Oct 2022

Priority

7 Oct 2021

Published

13 Feb 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification28 codes

C07K 16/2809
Against the immunoglobulin superfamily: against the T-cell receptor -CD3 complex
G01N 33/575
Immunoassay; Biospecific binding assay; Materials therefor: for cancer
A61K 39/39
Medicinal preparations containing antigens or antibodies: characterised by the immunostimulating additives, e.g. chemical adjuvants
A61K 47/6807
Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates: the drug or compound being a sugar, nucleoside, nucleotide,…

Anti-cd3 monoclonal antibodies and therapeutic constructs

Life of this patent

Anti-cd3 monoclonal antibodies and therapeutic constructs

Life of this patent

Abstract

Claims75