US2020055935A1PendingUtilityA1
Anti-TIM-3 Antibodies
Est. expiryOct 27, 2034(~8.2 yrs left)· nominal 20-yr term from priority
A61P 35/00A61P 31/00A61P 37/00A61P 37/04A61K 2039/505G01N 2333/70503C07K 2317/31C07K 2317/622G01N 2800/26G01N 2333/7051C07K 16/2803A61K 39/395G01N 33/6893C07K 16/2809C07K 16/28C07K 2317/73
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Claims
Abstract
Anti-TIM-3 antibodies are disclosed. Also disclosed are pharmaceutical compositions comprising such antibodies, and uses and methods using the same.
Claims
exact text as granted — not AI-modified1 - 57 . (canceled)
58 . A method of treating cancer in a patient suffering from a cancer, comprising administering an effective amount of an antibody that binds to TIM-3, or antigen binding fragment thereof, to the patient, wherein the antibody or antigen binding fragment comprises:
(i) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 12)
EAWDYYVAAGY;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 32)
GYVAGSDA;
OR
(ii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 13)
DSWDSADASGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 33)
GYVAGFDD;
OR
(iii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 14)
DSWDYDYAAGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 34)
GYVAGFDS;
OR
(iv) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 15)
DSWDSYLAAGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 35)
GYVAGYDY;
OR
(v) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 16)
ESWDYDYASGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 36)
GYVAGSDA;
OR
(vi) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 17)
DSWDSSDSSGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 37)
GYVAGFDS;
OR
(vii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 18)
EAWDSAYAAGS;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 38)
GYYAGDDY;
OR
(viii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 19)
DSWDAALSAGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 39)
GYVAGYDY;
OR
(ix) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 20)
ESWDAAAAAGY;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 40)
GYVAGSDA.
59 . The method according to claim 58 , wherein the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of one of SEQ ID NOs: 21 to 29 ( FIG. 2 ), and the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of one of: SEQ ID NO:1 to 9 ( FIG. 1 ).
60 . The method according to claim 58 , wherein:
(i) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:21, and the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:1;
OR
(ii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:22, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:2;
OR
(iii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:23, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:3;
OR
(iv) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:24, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:4;
OR
(v) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:25, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:5;
OR
(vi) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:26, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:6;
OR
(vii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:27, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:7;
OR
(viii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:28, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:8;
OR
(ix) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:29, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:9.
61 . The method according to claim 58 , wherein the antibody or the antigen binding fragment is a bispecific antibody or a bispecific antigen binding fragment of the antibody, further comprising an antigen binding domain which binds to a target protein other than TIM-3.
62 . The method according to claim 61 , wherein the antigen binding domain which binds to a target protein other than TIM-3 binds to CD3 or a CD3 polypeptide.
63 . The method according to claim 58 , wherein the antigen binding fragment is a Fab fragment or scFv fragment.
64 . The method according to claim 58 , wherein the antibody comprises a human constant region selected from IgG1, IgG2, IgG3 and IgG4.
65 . The method according to claim 58 , wherein the cancer is a cancer of a tissue selected from the group consisting of: lung, kidney, bladder, liver, stomach, cervix, naso pharynx, oral cavity, oesophagus, larynx, salivary gland, tongue, tonsil, trachea, skin, bloo d, colon and breast.
66 . The method according to claim 58 , wherein the cancer is selected from the gr oup consisting of lung cancer, non-small cell lung cancer (NSCLC), renal cancer, renal c ell carcinoma, bladder cancer, bladder carcinoma, liver cancer, hepatoma, stomach cancer, cervical cancer, nasopharyngeal cancer, oral cavity cancer, oesophageal cancer, laryngeal cancer, salivary gland cancer, tongue cancer, tonsil cancer, tracheal cancer, skin cancer, m elanoma, metastatic melanoma, haematologic cancer, lymphoma, Hodgkin's lymphoma, col on cancer, colon carcinoma and breast cancer.
67 . A method of treating an infectious disease in a patient suffering from an infectious disease, comprising administering an effective amount of an antibody that binds to TIM-3, or antigen binding fragment thereof, to the patient, wherein the antibody or antigen binding fragment comprises:
(i) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 12)
EAWDYYVAAGY;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 32)
GYVAGSDA;
OR
(ii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 13)
DSWDSADASGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 33)
GYVAGFDD;
OR
(iii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO:14)
DSWDYDYAAGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 34)
GYVAGFDS;
OR
(iv) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 15)
DSWDSYLAAGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 35)
GYVAGYDY;
OR
(v) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO:16)
ESWDYDYASGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 36)
GYVAGSDA;
OR
(vi) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 17)
DSWDSSDSSGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 37)
GYVAGFDS;
OR
(vii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 18)
EAWDSAYAAGS;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 38)
GYYAGDDY;
OR
(viii) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 19)
DSWDAALSAGV;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 39)
GYVAGYDY;
OR
(ix) at least one light chain variable region incorporating the following CDRs:
LC-CDR1:
(SEQ ID NO: 10)
SGSSSNIGNNYVS
LC-CDR2:
(SEQ ID NO: 11)
GNNWRPS
LC-CDR3:
(SEQ ID NO: 20)
ESWDAAAAAGY;
and
at least one heavy chain variable region incorporating the following CDRs:
HC-CDR1:
(SEQ ID NO: 61)
GYYWS,
or
(SEQ ID NO: 30)
GGSFSGYYWS
HC-CDR2:
(SEQ ID NO: 31)
EINHSGSTNYNPSLKS
HC-CDR3:
(SEQ ID NO: 40)
GYVAGSDA.
68 . The method according to claim 67 , wherein the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of one of SEQ ID NOs: 21 to 29 ( FIG. 2 ), and the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of one of: SEQ ID NO:1 to 9 ( FIG. 1 ).
69 . The method according to claim 67 , wherein:
(i) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:21, and the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:1;
OR
(ii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:22, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:2;
OR
(iii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:23, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:3;
OR
(iv) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:24, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:4;
OR
(v) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:25, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:5;
OR
(vi) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:26, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:6;
OR
(vii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:27, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:7;
OR
(viii) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:28, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:8;
OR
(ix) the heavy chain variable region has at least 85% sequence identity to the heavy chain variable region sequence of SEQ ID NO:29, and
the light chain variable region has at least 85% sequence identity to the light chain variable region sequence of SEQ ID NO:9.
70 . The method according to claim 67 , wherein the antibody or the antigen binding fragment is a bispecific antibody or a bispecific antigen binding fragment of the antibody, further comprising an antigen binding domain which binds to a target protein other than TIM-3.
71 . The method according to claim 70 , wherein the antigen binding domain which binds to a target protein other than TIM-3 binds to CD3 or a CD3 polypeptide.
72 . The method according to claim 67 , wherein the antigen binding fragment is a Fab fragment or scFv fragment.
73 . The method according to claim 67 , wherein the antibody comprises a human constant region selected from IgG1, IgG2, IgG3 and IgG4.Join the waitlist — get patent alerts
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