US 12,377,162 B2Granted

Anti-serine protease inhibitor kazal (SPIK) antibodies, immunoconjugates, and methods of use

AssigneeImCare Biotech, LLC

InventorsXuanyong Lu, Felix Lu

Life of this patent

Estimating the term…

Abstract

Anti-AS-SPIK antibodies are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to diagnose and/or treat disorders characterized by the expression of AS-SPIK (e.g., liver cancer). Diagnostic methods and kits comprising the anti-AS-SPIK antibodies are also disclosed.

Claims20

Dependent claims

An antibody or antigen-binding fragment thereof, that specifically binds to AS-SPIK (SEQ ID NO:

82), and does not bind to NS-SPIK (SEQ ID NO:
83), comprising:
(a) a CDRH1 sequence of SEQ ID NO:
21, a CDRH2 sequence of SEQ ID NO:
31, a CDRH3 sequence of SEQ ID NO:
41, a CDRL1 sequence of SEQ ID NO:
51, a CDRL2 sequence of SEQ ID NO:
61, and a CDRL3 sequence of SEQ ID NO:
71;
or
(b) a CDRH1 sequence of SEQ ID NO:
22, a CDRH2 sequence of SEQ ID NO:
32, a CDRH3 sequence of SEQ ID NO:
42, a CDRL1 sequence of SEQ ID NO:
52, a CDRL2 sequence of SEQ ID NO:
62, and a CDRL3 sequence of SEQ ID NO:
72;
or
(c) a CDRH1 sequence of SEQ ID NO:
23, a CDRH2 sequence of SEQ ID NO:
33, a CDRH3 sequence of SEQ ID NO:
43, a CDRL1 sequence of SEQ ID NO:
53, a CDRL2 sequence of SEQ ID NO:
63, and a CDRL3 sequence of SEQ ID NO:
73;
or
(d) a CDRH1 sequence of SEQ ID NO:
24, a CDRH2 sequence of SEQ ID NO:
34, a CDRH3 sequence of SEQ ID NO:
44, a CDRL1 sequence of SEQ ID NO:
54, a CDRL2 sequence of SEQ ID NO:
64, and a CDRL3 sequence of SEQ ID NO:
74;
or
(e) a CDRH1 sequence of SEQ ID NO:
25, a CDRH2 sequence of SEQ ID NO:
35, a CDRH3 sequence of SEQ ID NO:
45, a CDRL1 sequence of SEQ ID NO:
55, a CDRL2 sequence of SEQ ID NO:
65, and a CDRL3 sequence of SEQ ID NO:
75;
or
(f) a CDRH1 sequence of SEQ ID NO:
26, a CDRH2 sequence of SEQ ID NO:
36, a CDRH3 sequence of SEQ ID NO:
46, a CDRL1 sequence of SEQ ID NO:
56, a CDRL2 sequence of SEQ ID NO:
66, and a CDRL3 sequence of SEQ ID NO:
76;
or
(g) a CDRH1 sequence of SEQ ID NO:
27, a CDRH2 sequence of SEQ ID NO:
37, a CDRH3 sequence of SEQ ID NO:
47, a CDRL1 sequence of SEQ ID NO:
57, a CDRL2 sequence of SEQ ID NO:
67, and a CDRL3 sequence of SEQ ID NO:
77;
or
(h) a CDRH1 sequence of SEQ ID NO:
28, a CDRH2 sequence of SEQ ID NO:
38, a CDRH3 sequence of SEQ ID NO:
48, a CDRL1 sequence of SEQ ID NO:
58, a CDRL2 sequence of SEQ ID NO:
68, and a CDRL3 sequence of SEQ ID NO:
78;
or
(i) a CDRH1 sequence of SEQ ID NO:
29, a CDRH2 sequence of SEQ ID NO:
39, a CDRH3 sequence of SEQ ID NO:
49, a CDRL1 sequence of SEQ ID NO:
59, a CDRL2 sequence of SEQ ID NO:
69, and a CDRL3 sequence of SEQ ID NO:
79;
or
(j) a CDRH1 sequence of SEQ ID NO:
30, a CDRH2 sequence of SEQ ID NO:
40, a CDRH3 sequence of SEQ ID NO:
50, a CDRL1 sequence of SEQ ID NO:
60, a CDRL2 sequence of SEQ ID NO:
70, and a CDRL3 sequence of SEQ ID NO:
80.

78 more elements

A diagnostic method for determining whether a subject has or is at risk of developing a disorder characterized by expression of AS-SPIK, the method comprising:

(a) contacting a biological test sample from the subject with an anti-AS-SPIK antibody, or an antigen-binding fragment thereof, that specifically binds to AS-SPIK (SEQ ID NO:
82), and does not bind to NS-SPIK (SEQ ID NO:
83), to generate an AS-SPIK-antibody complex, wherein the anti-AS-SPIK antibody or antigen-binding fragment thereof comprises:
(i) a CDRH1 sequence of SEQ ID NO:
21, a CDRH2 sequence of SEQ ID NO:
31, a CDRH3 sequence of SEQ ID NO:
41, a CDRL1 sequence of SEQ ID NO:
51, a CDRL2 sequence of SEQ ID NO:
61, and a CDRL3 sequence of SEQ ID NO:
71;
or
(ii) a CDRH1 sequence of SEQ ID NO:
22, a CDRH2 sequence of SEQ ID NO:
32, a CDRH3 sequence of SEQ ID NO:
42, a CDRL1 sequence of SEQ ID NO:
52, a CDRL2 sequence of SEQ ID NO:
62, and a CDRL3 sequence of SEQ ID NO:
72;
or
(iii) a CDRH1 sequence of SEQ ID NO:
23, a CDRH2 sequence of SEQ ID NO:
33, a CDRH3 sequence of SEQ ID NO:
43, a CDRL1 sequence of SEQ ID NO:
53, a CDRL2 sequence of SEQ ID NO:
63, and a CDRL3 sequence of SEQ ID NO:
73;
or
(iv) a CDRH1 sequence of SEQ ID NO:
24, a CDRH2 sequence of SEQ ID NO:
34, a CDRH3 sequence of SEQ ID NO:
44, a CDRL1 sequence of SEQ ID NO:
54, a CDRL2 sequence of SEQ ID NO:
64, and a CDRL3 sequence of SEQ ID NO:
74;
or
(v) a CDRH1 sequence of SEQ ID NO:
25, a CDRH2 sequence of SEQ ID NO:
35, a CDRH3 sequence of SEQ ID NO:
45, a CDRL1 sequence of SEQ ID NO:
55, a CDRL2 sequence of SEQ ID NO:
65, and a CDRL3 sequence of SEQ ID NO:
75;
or
(vi) a CDRH1 sequence of SEQ ID NO:
26, a CDRH2 sequence of SEQ ID NO:
36, a CDRH3 sequence of SEQ ID NO:
46, a CDRL1 sequence of SEQ ID NO:
56, a CDRL2 sequence of SEQ ID NO:
66, and a CDRL3 sequence of SEQ ID NO:
76;
or
(vii) a CDRH1 sequence of SEQ ID NO:
27, a CDRH2 sequence of SEQ ID NO:
37, a CDRH3 sequence of SEQ ID NO:
47, a CDRL1 sequence of SEQ ID NO:
57, a CDRL2 sequence of SEQ ID NO:
67, and a CDRL3 sequence of SEQ ID NO:
77;
or
(viii) a CDRH1 sequence of SEQ ID NO:
28, a CDRH2 sequence of SEQ ID NO:
38, a CDRH3 sequence of SEQ ID NO:
48, a CDRL1 sequence of SEQ ID NO:
58, a CDRL2 sequence of SEQ ID NO:
68, and a CDRL3 sequence of SEQ ID NO:
78;
or
(ix) a CDRH1 sequence of SEQ ID NO:
29, a CDRH2 sequence of SEQ ID NO:
39, a CDRH3 sequence of SEQ ID NO:
49, a CDRL1 sequence of SEQ ID NO:
59, a CDRL2 sequence of SEQ ID NO:
69, and a CDRL3 sequence of SEQ ID NO:
79;
or
(x) a CDRH1 sequence of SEQ ID NO:
30, a CDRH2 sequence of SEQ ID NO:
40, a CDRH3 sequence of SEQ ID NO:
50, a CDRL1 sequence of SEQ ID NO:
60, a CDRL2 sequence of SEQ ID NO:
70, and a CDRL3 sequence of SEQ ID NO:
80;
(b) detecting a concentration of the AS-SPIK-antibody complex in the biological test sample;
and
(c) comparing the concentration of the AS-SPIK-antibody complex to a reference value to determine whether the subject has or is at risk of developing the disorder.

82 more elements

A kit comprising an anti-AS-SPIK antibody, or an antigen-binding fragment thereof, that specifically binds to AS-SPIK (SEQ ID NO:

82), and does not bind to NS-SPIK (SEQ ID NO:
83), comprising:
(a) a CDRH1 sequence of SEQ ID NO:
21, a CDRH2 sequence of SEQ ID NO:
31, a CDRH3 sequence of SEQ ID NO:
41, a CDRL1 sequence of SEQ ID NO:
51, a CDRL2 sequence of SEQ ID NO:
61, and a CDRL3 sequence of SEQ ID NO:
71;
or
(b) a CDRH1 sequence of SEQ ID NO:
22, a CDRH2 sequence of SEQ ID NO:
32, a CDRH3 sequence of SEQ ID NO:
42, a CDRL1 sequence of SEQ ID NO:
52, a CDRL2 sequence of SEQ ID NO:
62, and a CDRL3 sequence of SEQ ID NO:
72;
or
(c) a CDRH1 sequence of SEQ ID NO:
23, a CDRH2 sequence of SEQ ID NO:
33, a CDRH3 sequence of SEQ ID NO:
43, a CDRL1 sequence of SEQ ID NO:
53, a CDRL2 sequence of SEQ ID NO:
63, and a CDRL3 sequence of SEQ ID NO:
73;
or
(d) a CDRH1 sequence of SEQ ID NO:
24, a CDRH2 sequence of SEQ ID NO:
34, a CDRH3 sequence of SEQ ID NO:
44, a CDRL1 sequence of SEQ ID NO:
54, a CDRL2 sequence of SEQ ID NO:
64, and a CDRL3 sequence of SEQ ID NO:
74;
or
(e) a CDRH1 sequence of SEQ ID NO:
25, a CDRH2 sequence of SEQ ID NO:
35, a CDRH3 sequence of SEQ ID NO:
45, a CDRL1 sequence of SEQ ID NO:
55, a CDRL2 sequence of SEQ ID NO:
65, and a CDRL3 sequence of SEQ ID NO:
75;
or
(f) a CDRH1 sequence of SEQ ID NO:
26, a CDRH2 sequence of SEQ ID NO:
36, a CDRH3 sequence of SEQ ID NO:
46, a CDRL1 sequence of SEQ ID NO:
56, a CDRL2 sequence of SEQ ID NO:
66, and a CDRL3 sequence of SEQ ID NO:
76;
or
(g) a CDRH1 sequence of SEQ ID NO:
27, a CDRH2 sequence of SEQ ID NO:
37, a CDRH3 sequence of SEQ ID NO:
47, a CDRL1 sequence of SEQ ID NO:
57, a CDRL2 sequence of SEQ ID NO:
67, and a CDRL3 sequence of SEQ ID NO:
77;
or
(h) a CDRH1 sequence of SEQ ID NO:
28, a CDRH2 sequence of SEQ ID NO:
38, a CDRH3 sequence of SEQ ID NO:
48, a CDRL1 sequence of SEQ ID NO:
58, a CDRL2 sequence of SEQ ID NO:
68, and a CDRL3 sequence of SEQ ID NO:
78;
or
(i) a CDRH1 sequence of SEQ ID NO:
29, a CDRH2 sequence of SEQ ID NO:
39, a CDRH3 sequence of SEQ ID NO:
49, a CDRL1 sequence of SEQ ID NO:
59, a CDRL2 sequence of SEQ ID NO:
69, and a CDRL3 sequence of SEQ ID NO:
79;
or
(j) a CDRH1 sequence of SEQ ID NO:
30, a CDRH2 sequence of SEQ ID NO:
40, a CDRH3 sequence of SEQ ID NO:
50, a CDRL1 sequence of SEQ ID NO:
60, a CDRL2 sequence of SEQ ID NO:
70, and a CDRL3 sequence of SEQ ID NO:
80.

78 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/625,693Filed 8 Jul 2020 · us provisional application
Priority: 8 Jul 2019
Published: US 2022/0273810 A11 Sep 2022
Granted: 5 Aug 2025
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

A61K 47/6843
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a material from…
A61K 47/542
The modifying agent being an organic compound: carboxylic acids, e.g. a fatty acid or an amino acid
A61K 47/6817
The drug being a protein or peptide, e.g. transferrin or bleomycin: toxins
A61P 35/00
Antineoplastic agents

Family

Application62/871,565Us provisional application · filed 8 Jul 2019
US 2022/0273810 A1Pre-grant publication · published 1 Sep 2022
US 12,377,162 B2This patent

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

Timeline

Citations

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Abstract

An antibody or antigen-binding fragment thereof, that specifically binds to AS-SPIK (SEQ ID NO:

82), and does not bind to NS-SPIK (SEQ ID NO:
83), comprising:
(a) a CDRH1 sequence of SEQ ID NO:
21, a CDRH2 sequence of SEQ ID NO:
31, a CDRH3 sequence of SEQ ID NO:
41, a CDRL1 sequence of SEQ ID NO:
51, a CDRL2 sequence of SEQ ID NO:
61, and a CDRL3 sequence of SEQ ID NO:
71;
or
(b) a CDRH1 sequence of SEQ ID NO:
22, a CDRH2 sequence of SEQ ID NO:
32, a CDRH3 sequence of SEQ ID NO:
42, a CDRL1 sequence of SEQ ID NO:
52, a CDRL2 sequence of SEQ ID NO:
62, and a CDRL3 sequence of SEQ ID NO:
72;
or
(c) a CDRH1 sequence of SEQ ID NO:
23, a CDRH2 sequence of SEQ ID NO:
33, a CDRH3 sequence of SEQ ID NO:
43, a CDRL1 sequence of SEQ ID NO:
53, a CDRL2 sequence of SEQ ID NO:
63, and a CDRL3 sequence of SEQ ID NO:
73;
or
(d) a CDRH1 sequence of SEQ ID NO:
24, a CDRH2 sequence of SEQ ID NO:
34, a CDRH3 sequence of SEQ ID NO:
44, a CDRL1 sequence of SEQ ID NO:
54, a CDRL2 sequence of SEQ ID NO:
64, and a CDRL3 sequence of SEQ ID NO:
74;
or
(e) a CDRH1 sequence of SEQ ID NO:
25, a CDRH2 sequence of SEQ ID NO:
35, a CDRH3 sequence of SEQ ID NO:
45, a CDRL1 sequence of SEQ ID NO:
55, a CDRL2 sequence of SEQ ID NO:
65, and a CDRL3 sequence of SEQ ID NO:
75;
or
(f) a CDRH1 sequence of SEQ ID NO:
26, a CDRH2 sequence of SEQ ID NO:
36, a CDRH3 sequence of SEQ ID NO:
46, a CDRL1 sequence of SEQ ID NO:
56, a CDRL2 sequence of SEQ ID NO:
66, and a CDRL3 sequence of SEQ ID NO:
76;
or
(g) a CDRH1 sequence of SEQ ID NO:
27, a CDRH2 sequence of SEQ ID NO:
37, a CDRH3 sequence of SEQ ID NO:
47, a CDRL1 sequence of SEQ ID NO:
57, a CDRL2 sequence of SEQ ID NO:
67, and a CDRL3 sequence of SEQ ID NO:
77;
or
(h) a CDRH1 sequence of SEQ ID NO:
28, a CDRH2 sequence of SEQ ID NO:
38, a CDRH3 sequence of SEQ ID NO:
48, a CDRL1 sequence of SEQ ID NO:
58, a CDRL2 sequence of SEQ ID NO:
68, and a CDRL3 sequence of SEQ ID NO:
78;
or
(i) a CDRH1 sequence of SEQ ID NO:
29, a CDRH2 sequence of SEQ ID NO:
39, a CDRH3 sequence of SEQ ID NO:
49, a CDRL1 sequence of SEQ ID NO:
59, a CDRL2 sequence of SEQ ID NO:
69, and a CDRL3 sequence of SEQ ID NO:
79;
or
(j) a CDRH1 sequence of SEQ ID NO:
30, a CDRH2 sequence of SEQ ID NO:
40, a CDRH3 sequence of SEQ ID NO:
50, a CDRL1 sequence of SEQ ID NO:
60, a CDRL2 sequence of SEQ ID NO:
70, and a CDRL3 sequence of SEQ ID NO:
80.

78 more elements

Facts

Application

17/625,693Filed 8 Jul 2020 · us provisional application

Priority

8 Jul 2019

Published

US 2022/0273810 A11 Sep 2022

Granted

5 Aug 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

A61K 47/6843
The modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site: the antibody targeting a material from…
A61K 47/542
The modifying agent being an organic compound: carboxylic acids, e.g. a fatty acid or an amino acid
A61K 47/6817
The drug being a protein or peptide, e.g. transferrin or bleomycin: toxins
A61P 35/00
Antineoplastic agents