US 2024/0216557 A1Published application

Radioligand binding to anti-dll3 antibodies for pretargeted pet imaging and therapeutic uses thereof

AssigneesMemorial Sloan Kettering Cancer Center, Sloan-Kettering Institute for Cancer Research, Memorial Hospital for Cancer and Allied Diseases, Tri-Institutional Therapeutics Discovery Institute, Inc.

InventorsJohn T. POIRIER, Charles Rudin, Jason Lewis, Abdul Khan, David Andrew, Xinlei Chen, Ivo C. Lorenz, Kathryn M. Tully, Salomon Tendler

Life of this patent

Estimating the term…

Abstract

The presently disclosed subject matter provides compositions and methods for in vivo diagnosis and treatment of diseases or disorders associated with DLL3. In particular, the presently disclosed subject matter provides novel anti-DLL3 antibodies-TCO conjugates, which can form a radioimmunoconjugate with a radioligand comprising a radioactive isotope.

Claims66

Dependent claims

An antibody-transcyclooctene (TCO) conjugate comprising an anti-DLL3 antibody or an antigen-binding fragment thereof comprising a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains;

and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains, wherein the heavy chain variable region and light chain variable region CDR3 domains are selected from the group consisting of:
a) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
3 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
6 and a conservative modification thereof;
b) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
13 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
16 and a conservative modification thereof;
c) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
22 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
23 and a conservative modification thereof;
d) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
30 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
33 and a conservative modification thereof;
e) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
39 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
41 and a conservative modification thereof;
f) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
48 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
51 and a conservative modification thereof;
g) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59 and a conservative modification thereof;
h) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
64 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
65 and a conservative modification thereof;
i) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
72 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
75 and a conservative modification thereof;
j) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
81 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82 and a conservative modification thereof;
k) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
89 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
91 and a conservative modification thereof;
l) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
98 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
101 and a conservative modification thereof;
m) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82 and a conservative modification thereof;
n) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
112 and a conservative modification thereof;
o) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
116 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
118 and a conservative modification thereof;
p) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125 and a conservative modification thereof;
q) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
130 and a conservative modification thereof;
r) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
137 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
140 and a conservative modification thereof;
s) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
145 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125 and a conservative modification thereof;
t) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
152 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82 and a conservative modification thereof;
u) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59 and a conservative modification thereof;
v) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
161 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
162 and a conservative modification thereof;
w) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
168 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
171 and a conservative modification thereof;
x) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
177 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
179 and a conservative modification thereof;
y) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
186 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
189 and a conservative modification thereof;
z) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
195 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
196 and a conservative modification thereof;
and
aa) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
203 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
204 and a conservative modification thereof.

107 more elements

Dependencies are inferred from the claim text.

Facts

Application: 18/589,649Filed 28 Feb 2024
Priority: 2 Sep 2021
Published: 4 Jul 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification12 codes

A61K 51/1096
Conjugates with carriers being antibodies: radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a…
C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
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…
A61K 47/6897
Pre-targeting systems involving an antibody for targeting specific cells: pre-targeting systems with two or three steps using antibody conjugates;…

Family

Application63/240,237Us provisional application · filed 2 Sep 2021
Application18/589,649Continuation
US 2024/0216557 A1This patent

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

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Radioligand binding to anti-dll3 antibodies for pretargeted pet imaging and therapeutic uses thereof

InventorsJohn T. POIRIER, Charles Rudin, Jason Lewis, Abdul Khan, David Andrew, Xinlei Chen, Ivo C. Lorenz, Kathryn M. Tully, Salomon Tendler

Life of this patent

Estimating the term…

Abstract

and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains, wherein the heavy chain variable region and light chain variable region CDR3 domains are selected from the group consisting of:
a) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
3 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
6 and a conservative modification thereof;
b) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
13 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
16 and a conservative modification thereof;
c) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
22 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
23 and a conservative modification thereof;
d) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
30 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
33 and a conservative modification thereof;
e) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
39 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
41 and a conservative modification thereof;
f) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
48 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
51 and a conservative modification thereof;
g) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59 and a conservative modification thereof;
h) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
64 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
65 and a conservative modification thereof;
i) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
72 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
75 and a conservative modification thereof;
j) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
81 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82 and a conservative modification thereof;
k) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
89 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
91 and a conservative modification thereof;
l) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
98 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
101 and a conservative modification thereof;
m) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82 and a conservative modification thereof;
n) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
107 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
112 and a conservative modification thereof;
o) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
116 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
118 and a conservative modification thereof;
p) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125 and a conservative modification thereof;
q) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
56 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
130 and a conservative modification thereof;
r) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
137 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
140 and a conservative modification thereof;
s) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
145 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
125 and a conservative modification thereof;
t) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
152 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
82 and a conservative modification thereof;
u) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
123 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
59 and a conservative modification thereof;
v) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
161 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
162 and a conservative modification thereof;
w) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
168 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
171 and a conservative modification thereof;
x) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
177 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
179 and a conservative modification thereof;
y) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
186 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
189 and a conservative modification thereof;
z) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
195 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
196 and a conservative modification thereof;
and
aa) a heavy chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
203 and a conservative modification thereof;
and a light chain variable region CDR3 comprising the amino acid sequence set forth in SEQ ID NO:
204 and a conservative modification thereof.

107 more elements

Facts

Application

18/589,649Filed 28 Feb 2024

Priority

2 Sep 2021

Published

4 Jul 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification12 codes

A61K 51/1096
Conjugates with carriers being antibodies: radioimmunotoxins, i.e. conjugates being structurally as defined in A61K51/1093, and including a…
C07K 16/28
Against material from animals or humans: against receptors, cell surface antigens or cell surface determinants
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…
A61K 47/6897
Pre-targeting systems involving an antibody for targeting specific cells: pre-targeting systems with two or three steps using antibody conjugates;…