Monoclonal antibody against human activated protein C and preparation and use thereof
The present disclosure belongs to the technical field of monoclonal antibodies, and relates to a monoclonal antibody against activated protein C (aPC). Amino acid sequences of a heavy chain and a light chain of the monoclonal antibody are shown in SEQ ID NOs: 5-26, and CDR sequences are shown in SEQ ID NOs: 27-92. The present disclosure further provides a biological material related to the monoclonal antibody, and the monoclonal antibody is capable of selectively binding to aPC rather than unactivated protein C. The present disclosure further provides use of the monoclonal antibody and the related biological material in preparation of a drug for treatment of coagulation deficiency or defect disorders and a related treatment method, which have broad application prospects.
1 . An anti-activated protein C (aPC) monoclonal antibody, wherein the anti-aPC monoclonal antibody is selected from one of the following:
an antibody comprising (a) heavy chain CDRs represented by SEQ ID NOs: 33, 34, and 35; and (b) light chain CDRs represented by SEQ ID NOs: 36, 37, and 38;
an antibody comprising (c) heavy chain CDRs represented by SEQ ID NOs: 39, 40, and 41; and (d) light chain CDRs represented by SEQ ID NOs: 42, 43, and 44;
an antibody comprising (e) heavy chain CDRs represented by SEQ ID NOs: 45, 46, and 47; and (f) light chain CDRs represented by SEQ ID NOs: 48, 49, and 50;
an antibody comprising (g) heavy chain CDRs represented by SEQ ID NOs: 51, 52, and 53; and (h) light chain CDRs represented by SEQ ID NOs: 54, 55, and 56;
an antibody comprising (i) heavy chain CDRs represented by SEQ ID NOs: 57, 58, and 59; and (i) light chain CDRs represented by SEQ ID NOs: 60, 61, and 62;
an antibody comprising (k) heavy chain CDRs represented by SEQ ID NOS: 63, 64, and 65; and (l) light chain CDRs represented by SEQ ID NOs: 66, 67, and 68;
an antibody comprising (m) heavy chain CDRs represented by SEQ ID NOs: 69, 70, and 71; and (n) light chain CDRs represented by SEQ ID NOs: 72, 73, and 74;
an antibody comprising (o) heavy chain CDRs represented by SEQ ID NOs: 75, 76, and 77; and (p) light chain CDRs represented by SEQ ID NOs: 78, 79, and 80;
an antibody comprising (q) heavy chain CDRs represented by SEQ ID NOs: 81, 82, and 83; and (r) light chain CDRs represented by SEQ ID NOs: 84, 85, and 86; and
an antibody comprising (s) heavy chain CDRs represented by SEQ ID NOs: 87, 88, and 89; and (t) light chain CDRs represented by SEQ ID NOs: 90, 91, and 92.
2 . The anti-aPC monoclonal antibody according to claim 1 , wherein the anti-aPC monoclonal antibody is selected from the following:
an antibody comprising a heavy chain as shown in SEQ ID NO: 7 and a light chain as shown in SEQ ID NO: 8;
an antibody comprising a heavy chain as shown in SEQ ID NO: 9 and a light chain as shown in SEQ ID NO: 10;
an antibody comprising a heavy chain as shown in SEQ ID NO: 11 and a light chain as shown in SEQ ID NO: 12;
an antibody comprising a heavy chain as shown in SEQ ID NO: 13 and a light chain as shown in SEQ ID NO: 14;
an antibody comprising a heavy chain as shown in SEQ ID NO: 15 and a light chain as shown in SEQ ID NO: 16;
an antibody comprising a heavy chain as shown in SEQ ID NO: 17 and a light chain as shown in SEQ ID NO: 18;
an antibody comprising a heavy chain as shown in SEQ ID NO: 19 and a light chain as shown in SEQ ID NO: 20;
an antibody comprising a heavy chain as shown in SEQ ID NO: 21 and a light chain as shown in SEQ ID NO: 22;
an antibody comprising a heavy chain as shown in SEQ ID NO: 23 and a light chain as shown in SEQ ID NO: 24; and
an antibody comprising a heavy chain as shown in SEQ ID NO: 25 and a light chain as shown in SEQ ID NO: 26.
3 . The anti-aPC monoclonal antibody according to claim 1 , wherein the anti-aPC monoclonal antibody is a complete antibody or an antibody fragment thereof; wherein the antibody fragment is Fab′, Fab, F(ab′)2, Fv or scFv.
4 . A biological material related to the anti-aPC monoclonal antibody according to claim 1 , wherein the biological material is any one of 1) to 3) as follows:
1) A nucleic acid molecule encoding the anti-aPC monoclonal antibody according to claim 1 ;
2) A construct containing the nucleic acid molecule as described in 1); and
3) An expression system containing the nucleic acid molecule as described in 1).
5 . A preparation product, wherein the preparation product is a pharmaceutical composition or a detection kit;
the preparation product comprises the anti-aPC monoclonal antibody according to claim 1 ; and
when being the pharmaceutical composition, the preparation product further comprises a pharmaceutically acceptable carrier.
6 . A method for treating coagulation related disorders, comprising administering to an individual in need of treatment an effective amount of the anti-aPC monoclonal antibody according to claim 1 ; wherein the individual suffers from coagulation deficiency or defect disorders, or the individual is in need of blood coagulation treatment, or the individual suffers from sepsis or hemophilia, or the individual is in need of regulation of hemostasis.
7 . The method according to claim 6 , wherein the coagulation deficiency or defect disorders comprise disorders causing coagulopathy due to deficiency of coagulation factors and thus causing bleeding, and coagulation disturbances caused by trauma or surgery.
8 . The method according to claim 7 , wherein the coagulation deficiency or defect disorders comprise hemophilia, sepsis and traumatic hemorrhage.
9 . A preparation product, wherein the preparation product is a pharmaceutical composition or a detection kit;
the preparation product comprises any one or more of the biological materials according to claim 4 ; and
when being the pharmaceutical composition, the preparation product further comprises a pharmaceutically acceptable carrier.
10 . A method for treating coagulation related disorders, comprising administering to an individual in need of treatment an effective amount of any one or more of the biological materials according to claim 4 ; wherein the individual suffers from coagulation deficiency or defect disorders, or the individual is in need of blood coagulation treatment, or the individual suffers from sepsis or hemophilia, or the individual is in need of regulation of hemostasis.
11 . A method for promoting the ability of activated protein C (aPC) in an individual to cleave histones H3 and H4, comprising administering to the individual in need an effective amount of the anti-aPC monoclonal antibody of claim 1 .
12 . A method of inhibiting the anticoagulant activity of activated protein C (aPC) in an individual, comprising administering to the individual in need an effective amount of the anti-aPC monoclonal antibody of claim 1 .
13 . A kit for detecting activated protein C (aPC) in a sample, comprising the anti-aPC monoclonal antibody of claim 1 .