Inhibition of platelet aggregation using anti- human gpvi antibodies

1 . A method for treating a cardiovascular disease or event associated with inflammation and/or thrombosis in a subject in need thereof, comprising administering to the subject an isolated humanized antibody or antibody fragment capable of binding to human Glycoprotein VI (hGPVI), and administering to the subject a thrombolytic agent,

wherein said isolated humanized antibody or antibody fragment comprises:

a heavy chain variable region comprising the following complementarity determining regions (CDRs):

variable heavy chain (VH)-CDR1:

(SEQ ID NO: 1)

GYTFTSYNMH;

VH-CDR2:

(SEQ ID NO: 2)

GIYPGNGDTSYNQKFQG;

and

VH-CDR3:

(SEQ ID NO: 3)

GTVVGDWYFDV;

and

a light chain variable region comprising the following CDRs:

variable light chain (VL)-CDR1:

(SEQ ID NO: 4)

RSSQSLENSNGNTYLN;

VL-CDR2:

(SEQ ID NO: 5)

RVSNRFS;

and

VL-CDR3:

(SEQ ID NO: 6)

LQLTHVPWT.

thereby treating the cardiovascular disease or event associated with inflammation and/or thrombosis in the subject.

2 . The method according to claim 1 , wherein said isolated humanized antibody or antibody fragment is selected from the group consisting of a whole antibody, a single chain antibody, a Fv, a Fab, and a unibody.

3 . The method according to claim 1 , wherein said isolated humanized antibody or antibody fragment is monovalent.

4 . The method according to claim 1 , wherein the amino acid sequence of the heavy chain variable region is SEQ ID NO: 7 and the amino acid sequence of the light variable region is SEQ ID NO: 8, or any sequence having an amino acid sequence that shares at least 60% of identity with said SEQ ID NO: 7 or 8.

5 . The method according to claim 1 , wherein the thrombolytic agent is tissue-type plasminogen activator (t-PA).

6 . The method according to claim 5 , wherein the t-PA is a native, a recombinant, or a modified form of t-PA.

7 . The method according to claim 1 , wherein the thrombolytic agent is administered before, concomitantly or after the administration of the isolated humanized antibody or antibody fragment.

8 . The method according to claim 1 , wherein said cardiovascular disease or event associated with inflammation and/or thrombosis is selected from the group consisting of arterial and venous thrombosis, restenosis, acute coronary syndrome, cerebrovascular accidents due to atherosclerosis, critical limb ischemia, cerebral vascular diseases including ischemic stroke, venous thromboembolism diseases, thrombotic microangiopathies, vascular purpura, coronary artery and cerebral artery diseases, atherothrombosis, ischemic events, myocardial infarction, stroke, percutaneous coronary intervention, stenting thrombosis, ischemic restenosis, acute ischemia, chronic ischemia, diseases of the aorta and its branches, peripheral artery disease, acute phlebitis, pulmonary embolism, cancer-associated thrombosis, inflammatory thrombosis and thrombosis associated to infection.

9 . The method according to claim 1 , wherein said subject was previously treated or is to be treated by endovascular treatment and/or thrombectomy.

10 . A kit of parts comprising, in a first part, at least one isolated humanized antibody or antibody fragment capable of binding to human Glycoprotein VI (hGPVI) and, in a second part, at least one tissue-type plasminogen activator (t-PA),

wherein the humanized antibody or antibody fragment comprises:

a heavy chain variable region comprising the following complementarity determining regions (CDRs):

variable heavy chain(VH)-CDR1:

(SEQ ID NO: 1)

GYTFTSYNMH;

VH-CDR2:

(SEQ ID NO: 2)

GIYPGNGDTSYNQKFQG;

and

VH-CDR3:

(SEQ ID NO: 3)

GTVVGDWYFDV;

a light chain variable region comprising the following CDRs:

variable light chain(VL)-CDR1:

(SEQ ID NO: 4)

RSSQSLENSNGNTYLN;

VL-CDR2:

(SEQ ID NO: 5)

RVSNRFS;

and

VL-CDR3:

(SEQ ID NO: 6)

LQLTHVPWT.

11 . The kit of parts according to claim 10 , wherein said t-PA is a native, a recombinant, or a modified form of t-PA.

12 . The kit of parts according to claim 10 , wherein the amino acid sequence of the heavy chain variable region is SEQ ID NO: 7 and the amino acid sequence of the light chain variable region is SEQ ID NO: 8, or any sequence having an amino acid sequence that shares at least 60% of identity with said SEQ ID NO: 7 or 8.