WO2023103789A1

WO2023103789A1 - Antibody specifically recognizing masp2 and use thereof

Info

Publication number: WO2023103789A1
Application number: PCT/CN2022/133888
Authority: WO
Inventors: 付文艳; 张超; 李忠
Original assignee: 舒泰神（北京）生物制药股份有限公司
Priority date: 2021-12-10
Filing date: 2022-11-24
Publication date: 2023-06-15
Also published as: CN116615544A

Abstract

Provided are an antibody or antigen-binding fragment that specifically recognizes MASP2, and a preparation method therefor and the use thereof.

Description

Antibody specifically recognizing MASP2 and its application

Cross References to Related Applications

This application claims the priority of the Chinese patent application with the application number 202111502635.8, the application date is 2021.12.10, and the invention title is "Antibody that specifically recognizes MASP2 and its application", and the entire content of this application is incorporated herein by reference .

References to Electronic Sequence Listings

The content of the electronic sequence listing (text name: CN_202112093252_SEQLIST.xml, record date: 2022.08.04, size: 80KB) is incorporated herein by reference in its entirety.

technical field

The present application relates to an antibody or an antigen-binding fragment specifically recognizing MASP2, its preparation method and use.

Background technique

The complement system is a major branch of the immune response, interacting with a variety of immune mechanisms in innate and adaptive immunity. It is mainly activated through cascades of three different pathways: the classical pathway (CP), the lectin pathway (LP) or the alternative pathway (AP). Although each pathway has different initiating factors as well as unique, specific factors, all involve the activation of C3 and C5 and lead to a common pathway, the formation of the membrane attack complex (MAC, C5b-9), which Binds to target cell membranes, causing cell lysis. Unique factors associated with LP activation include collagen lectins (mannose-binding lectin, collagen lectin-10, collagen lectin-11), ficolins (ficolin 1, ficolin 2, ficolin lectin 3) and proteins of the mannose-binding lectin-associated serine protease (MASP) family (MASP-1, MASP-2, MASP-3, MAp19, MAp44). Mannose-binding lectins, collagen lectin proteins, ficolins are all pattern recognition molecules (PRMs) that react with pathogen-associated pattern molecules (PAMPs) or damage-associated pattern molecules (DAMPs). DAMPs include endogenous ligands, eg, aberrantly glycosylated host cell surface structures. Although complement activation relies on the direct lysis of pathogens/abnormal self cells, these factors can act as opsonins, thereby facilitating phagocytosis (Cedzyński, Maciej, and Anna S

Cancers vol.12,7 1792.4Jul.2020).

Dimers, trimers and/or higher oligomers of these trimeric structural subunits of PRMs form complexes with homodimers of MASPs, which initially form as enzyme precursors (zymogen) form (Kjaer,Troels R et al. Molecular immunology vol.56,4(2013):413-22). When PRMs bind to their targets, MASPs are cleaved and activated (Dahl, M R et al. Immunity vol.15,1(2001):127-35.; Degn,

E et al. Journal of immunology (Baltimore, Md.: 1950) vol.183, 11 (2009): 7371-8.; Héja, Dávid et al. Proceedings of the National Academy of Sciences of the United States of America vol. 109, 26(2012):10498-503.). Although MASP-2 can be self-activated, it has long been considered a central activator of the lectin pathway (Ambrus, Géza et al. Journal of immunology (Baltimore, Md.: 1950) vol. 170, 3(2003): 1374- 82.; Gál, Péter et al. The Journal of biological chemistry vol.280,39(2005):33435-44.; Matsushita, M et al.Journal of immunology (Baltimore, Md.:1950) vol. 165,5 (2000):2637-42), but recent evidence from different authors suggests that MASP-1 is also self-activating and plays an important role in activating MASP-2 (Degn,

E et al. Journal of immunology (Baltimore, Md.:1950) vol.189,8(2012):3957-69.; Héja, Dávid et al. Proceedings of the National Academy of Sciences of the United States of America vol. 109, 26(2012): 10498-503.; Kjaer, Troels R et al. Molecular immunology vol. 56, 4(2013): 413-22.).

Activated MASP-2 cleaves complement components C4 and C2 to generate the C3 convertase C4bC2a. MASP-1 can also cleave C2. C3 convertase cleaves C3 to C3b, which amplifies the cascade and mediates phagocytosis, as well as the adaptive immune response. Addition of an additional C3b molecule to the C3 convertase forms a C5 convertase (C4bC2aC3b). C3b serves as the binding site for C5, which initiates the assembly of the membrane attack complex (MAC) by cleaving C5 into C5a and C5b. C5a is a potent anaphylatoxin, while C5b forms a complex with C6 and C7 and inserts into the cell membrane. Thereafter, C8 and 10-18 C9 molecules associate with this complex to form a fully functional MAC (C5b-9), which eventually leads to cell lysis and death (Beltrame, Marcia H et al. Molecular immunology vol.67,1( 2015):85-100). In addition, it can activate prothrombin, thereby participating in the activation of the coagulation system (Garred, Peter et al. Immunological reviews vol.274,1(2016):74-97.)

The results of several seminal studies have shown that MASP2 is not only important in the activation of the lectin pathway but also in the generation of fibrin clots in the coagulation cascade. MASP-2 levels are also associated with many diseases, including schizophrenia (Mayilyan,Karine R et al.Neuroscience letters vol.404,3(2006):336-41), septic shock (Charchaflieh,Jean et al.Clinical&developmental immunology vol.2012(2012):407324.), acute lymphoblastic leukemia, non-Hodgkin's lymphoma, central nervous system tumors (Fisch, Urs P et al. Swiss medical weekly vol.141w13191.29Apr.2011.), colorectal Cancer (Ytting, Henriette et al.Clinical cancer research: an official journal of the American Association for Cancer Research vol.11,4(2005):1441-6.; Ytting, Henriette et al.Human immunology vol.69,7( 2008): 414-20.), thrombotic microangiopathy (Elhadad, S et al. Clinical and experimental immunology vol.203,1(2021): 96-104), systemic lupus erythematosus (Xu, Wang-Dong et al .Journal of cellular and molecular medicine vol.24,18(2020):10432-10443), IgA nephropathy (Lafayette,Richard A et al.Kidney international reports vol.5,11 2032-2041.13Aug.2020), COVID-19 (Rambaldi, Alessandro et al. Immunobiology vol. 225, 6(2020): 152001) and so on. Therefore, it is crucial to develop inhibitors against MASP2.

At present, there have been reports on antibodies against MASP2. For example, Chinese patent CN103687620B discloses the anti-MASP2 antibody OMS721 (as a control antibody in the Examples of this application) and its application. Anti-MASP2 antibodies with high affinity and high biological activity are still needed in the existing therapeutic field.

The disclosures in all publications, patents, patent applications, and published patent applications mentioned herein are hereby incorporated by reference in their entirety.

Application overview

In some embodiments, there is provided an isolated anti-MASP2 antibody comprising: a heavy chain _variable domain ( _VH ) comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SDYAWN( SEQ ID NO:1); HC-CDR2, which comprises YISYSGRTSYNPSLKS (SEQ ID NO:5); and HC-CDR3, which comprises HYGX ₁ X ₂ (SEQ ID NO:38), wherein X ₁ is D or S, X ₂ is H or _Y ; and a light chain variable domain (V _L ) comprising: light chain complementarity determining region (LC-CDR) 1 comprising KASQNVGTNVA (SEQ ID NO: 19); LC-CDR2 , which comprises SASYRYS (SEQ ID NO:26); and LC-CDR3, which comprises X ₁ QYNSX ₂ X ₃ X ₄ (SEQ ID NO:39), wherein X ₁ is H or Q, X ₂ is N or Y, X ₃ is L or P, X ₄ is L or T.

In some embodiments, an isolated anti-MASP2 antibody is provided, comprising: _VH comprising: HC- _CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1; HC-CDR2 comprising the amino acid sequence shown in SEQ ID NO: 5; and HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 13-14 or a variant thereof comprising a substitution of up to about 3 amino acids and V _L , said V _L comprising: LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:19; LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:26; and LC-CDR3, It comprises the amino acid sequence shown in any one of SEQ ID NOs: 30-31 or a variant thereof comprising a substitution of up to about 3 amino acids.

In some embodiments, an isolated anti-MASP2 antibody is provided, comprising: _VH , said _VH comprising HC-CDR1 comprised by _VH as shown in any one of the amino acid sequences of SEQ ID NOs: 40 or 44, HC-CDR2 and HC-CDR3, and _VL , said _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in any one of the amino acid sequences of SEQ ID NOs:62 or 65.

In some embodiments, an isolated anti-MASP2 antibody is provided, comprising: (i) _VH comprising HC-CDR1, HC-CDR2 and HC comprised by _VH as shown in the amino acid sequence of SEQ ID NO:40 -CDR3; and V _L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 contained in V _L as shown in the amino acid sequence SEQ ID NO:62; or (ii) V _H , which comprises the amino acid sequence SEQ ID HC-CDR1, HC-CDR2 and HC-CDR3 contained in V _H shown in NO:44; and V _L , which comprises LC-CDR1 and LC-CDR2 contained in V _L shown in amino acid sequence SEQ ID NO:65 and LC-CDR3.

In some embodiments, there is provided an isolated anti-MASP2 antibody comprising: (i) _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 13, or variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and _VL , The _VL comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or A variant of said V _L comprising a substitution of up to about 5 amino acids in its LC-CDRs; or (ii) V _H comprising: HC- _CDR1 comprising the amino acid sequence SEQ ID NO: 1, HC - CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14, or a variant of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs and V _L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26 _, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant of said _VL comprising up to about 5 amino acid substitutions in its LC-CDRs.

In some embodiments, any of the isolated anti-MASP2 antibodies as described above, comprising: V _H comprising the amino acid sequence shown in any one of SEQ ID NOs: 40-47 or a variant thereof, said variant Having at least about 80% sequence identity with the amino acid sequence shown in any of SEQ ID NOs: 40-47; and V _L comprising the amino acid sequence shown in any of SEQ ID NOs: 62-68 or a variant thereof , the variant has at least about 80% sequence identity to the amino acid sequence shown in any one of SEQ ID NOs: 62-68.

In some embodiments, there is provided an isolated anti-MASP2 antibody comprising: (i) V _H comprising the amino acid sequence of SEQ ID NO: 40 or a variant thereof having at least the same length as the amino acid sequence of SEQ ID NO: 40 about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 62; (ii) V _H comprising the amino acid sequence of SEQ ID NO:41 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:41; and V _L comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63; (iii) V _H comprising the amino acid sequence of SEQ ID NO:41 or a variant thereof, said variant Having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:41; and V _L comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence identity; (iv) _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 42; and _VL , which comprises the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63; (v) V _H , which comprises the amino acid sequence of SEQ ID NO: 42 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 42; and V _L comprising the amino acid sequence SEQ ID NO: 64 or a variant thereof which is identical to The amino acid sequence of SEQ ID NO:64 has at least about 80% sequence identity; (vi) V _H comprising the amino acid sequence of SEQ ID NO:43 or a variant thereof having at least about 80% identity to the amino acid sequence of SEQ ID NO:43 about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63; (vii) V _H comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 43; and V _L comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:64; (viii) V _H comprising the amino acid sequence of SEQ ID NO:44 or a variant thereof, said variant Having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:44; and V _L comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence identity; (ix) _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 45; and _VL , which comprises the amino acid sequence of SEQ ID NO: 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 66; (x) V _H , which comprises the amino acid sequence of SEQ ID NO: 46 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 46; and V _L comprising the amino acid sequence SEQ ID NO: 66 or a variant thereof which is identical to The amino acid sequence of SEQ ID NO:66 has at least about 80% sequence identity; (xi) V _H comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof having at least about 80% identity to the amino acid sequence of SEQ ID NO:47 about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 66; (xii) V _H comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 45; and V _L comprising the amino acid sequence of SEQ ID NO: 67 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67; (xiii) V _H comprising the amino acid sequence of SEQ ID NO:46 or a variant thereof, said variant Having at least about 80% sequence identity with the amino acid sequence of SEQ ID NO:46; and V _L comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence identity; (xiv) _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 47; and _VL , which comprises the amino acid sequence of SEQ ID NO: 67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 67; (xv) V _H , which comprises the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 45; and V _L comprising the amino acid sequence SEQ ID NO: 68 or a variant thereof which is identical to The amino acid sequence of SEQ ID NO:68 has at least about 80% sequence identity; (xvi) V _H comprising the amino acid sequence of SEQ ID NO:46 or a variant thereof having at least about 80% identity to the amino acid sequence of SEQ ID NO:46 about 80% sequence identity; and _VL comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 68; or (xvii) _VH comprising the amino acid sequence of SEQ ID NO:47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:47; and _VL comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68.

In some embodiments, an isolated anti-MASP2 antibody is provided, comprising: (i) _VH comprising HC-CDR1, HC-CDR2 and HC comprised by _VH as shown in the amino acid sequence of SEQ ID NO:48 -CDR3; and V _L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 contained in V _L as shown in the amino acid sequence SEQ ID NO:69; (ii) V _H , which comprises the amino acid sequence SEQ ID NO HC-CDR1, HC- _CDR2 and HC-CDR3 contained in the V _H shown in: 49; and V _L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3; (iii) V _H , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 contained in V _H as shown in the amino acid sequence SEQ ID NO:50; and V _L , which comprises the amino acid sequence SEQ ID LC-CDR1, LC-CDR2 and LC-CDR3 contained in V _L shown in NO:71; (iv) V _H , it comprises HC-CDR1, HC contained in V _H shown in amino acid sequence SEQ ID NO:51 - CDR2 and HC-CDR3; and V _L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 contained in V _L as shown in the amino acid sequence SEQ ID NO:72; (v) V _H , which comprises amino acids such as HC-CDR1, _HC -CDR2 and HC-CDR3 contained in the V _H shown in sequence SEQ ID NO:52; and V _L , which comprises LC-CDR1, LC-CDR2 and LC-CDR3; (vi) V _H , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 contained in V _H as shown in the amino acid sequence SEQ ID NO:53; and V _L , which comprises such as LC-CDR1, LC-CDR2 and LC-CDR3 contained in the V _L shown in the amino acid sequence SEQ ID NO:72; (vii) V _H comprising the HC contained in the V _H shown in the amino acid sequence SEQ ID NO:54 -CDR1, HC-CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in V _L as shown in the amino acid sequence SEQ ID NO:74; or (viii) V _H , which comprises HC-CDR1, HC-CDR2, and HC-CDR3 contained in V _H as shown in the amino acid sequence of SEQ ID NO:55; and V _L , which comprises the V _L contained in the amino acid sequence of SEQ ID NO:75 LC-CDR1, LC-CDR2 and LC-CDR3.

In some embodiments, there is provided an isolated anti-MASP2 antibody comprising: (i) _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 15, or variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and _VL , The _VL comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:20, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:27, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:32, or A variant of said V _L , comprising a substitution of up to about 5 amino acids in its LC-CDRs; (ii) V _H , said V _H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC- CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant of said _VH comprising a substitution of up to about 5 amino acids in the HC-CDRs; and V _L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:27 _, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO : 33, or a variant of said V _L comprising a substitution of up to about 5 amino acids in its LC-CDRs; (iii) V _H comprising: HC- _CDR1 comprising the amino acid sequence SEQ ID NO: 1. HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or a variant of said _VH comprising at most about 5 of its HC-CDRs amino acid substitutions; and _a _VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence Sequence SEQ ID NO: 31, or variants of said _VL comprising up to about 5 amino acid substitutions in its LC-CDRs; (iv) _VH comprising: HC- _CDR1 comprising the amino acid sequence SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or a variant of said _VH comprising in its HC-CDRs A substitution of up to about 5 amino acids; and a _VL comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO:22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:28, and LC-CDR3 , which comprises the amino acid sequence of SEQ ID NO: 34, or a variant of said V _L comprising a substitution of up to about 5 amino acids in its LC-CDRs; (v) V _H , said V _H comprising: HC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 9, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 18, or a variant of said _VH , its HC -CDRs comprising up to about 5 amino acid substitutions; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO:23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 35, or variants of said _VL comprising a substitution of up to about 5 amino acids in its LC-CDRs; (vi) _VH , said _VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or a variant of said _VH A body comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:34, or variants of said V _L , comprising a substitution of up to about 5 amino acids in its LC-CDRs; (vii) V _H , said The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or the A variant of _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and _VL comprising: LC-CDR1 comprising the amino acid sequence of _SEQ ID NO: 24, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or variants of said _VL comprising up to about 5 amino acid substitutions in the LC-CDRs; or (viii) V _H , said V _H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a _VL comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 23, LC - CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant of said V _L comprising a substitution of up to about 5 amino acids in its LC-CDRs .

In some embodiments, any of the isolated anti-MASP2 antibodies as described above, comprising: (i) V _H comprising the amino acid sequence shown in SEQ ID NO: 48 or a variant thereof, said variant being identical to SEQ ID NO: 48 The amino acid sequence set forth in ID NO:48 has at least about 80% sequence identity; and V _L , which comprises the amino acid sequence set forth in SEQ ID NO:69 or a variant thereof that is identical to that set forth in SEQ ID NO:69 The amino acid sequence shown has at least about 80% sequence identity; (ii) V _H , which comprises the amino acid sequence shown in SEQ ID NO:49 or a variant thereof that is identical to the amino acid sequence shown in SEQ ID NO:49 The sequence has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence set forth in SEQ ID NO:70 or a variant thereof having at least about 80% identity to the amino acid sequence set forth in SEQ ID NO:70 % sequence identity; (iii) _VH comprising the amino acid sequence shown in SEQ ID NO:50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO:50 and V _L comprising the amino acid sequence shown in SEQ ID NO:71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO:71; (iv) _VH comprising the amino acid sequence set forth in SEQ ID NO:51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:51; and _VL comprising The amino acid sequence shown in SEQ ID NO: 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 72; (v) V _H comprising SEQ ID NO : the amino acid sequence set forth in SEQ ID NO:52 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:52; and V _L comprising the amino acid sequence set forth in SEQ ID NO:73 an amino acid sequence or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:73; (vi) _VH comprising the amino acid sequence set forth in SEQ ID NO:53 or A variant thereof, which has at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:53; and V _L , which comprises the amino acid sequence set forth in SEQ ID NO:72 or a variant thereof, wherein said variant has at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:72; (vii) V _H comprising the amino acid sequence set forth in SEQ ID NO:54 or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:54; and V _L comprising the amino acid sequence set forth in SEQ ID NO:74 or a variant thereof that is identical to SEQ ID NO: The amino acid sequence shown in 74 has at least about 80% sequence identity; or (viii) _VH , it comprises the amino acid sequence shown in SEQ ID NO:55 or its variant, and described variant is identical with SEQ ID NO:55 The amino acid sequence shown has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence shown in SEQ ID NO:75 or its variant, and said variant has the amino acid sequence shown in SEQ ID NO:75 At least about 80% sequence identity.

In some embodiments, an isolated anti-MASP2 antibody is provided, comprising: _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence of SEQ ID NO:56; And _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence of SEQ ID NO:76.

In some embodiments, there is provided an isolated anti-MASP2 antibody comprising: _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:3 ID NO: 10, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 18, or variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and _VL , said V _L comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:25, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:37, or the V A variant of _L comprising up to about 5 amino acid substitutions in the LC-CDRs.

In some embodiments, any of the isolated anti-MASP2 antibodies described above, comprising: (i) _VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence of SEQ ID NO:56 has at least about 80% sequence identity; and _VL , it comprises amino acid sequence SEQ ID NO:76 or its variant, and said variant has at least about 80% sequence identity with amino acid sequence SEQ ID NO:76 (ii) V _H comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 57; and V _L comprising the amino acid sequence SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77; (iii) _VH comprising the amino acid sequence of SEQ ID NO:58 or a variant thereof , the variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 58; and V _L , comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof, said variant having the amino acid sequence of SEQ ID NO :77 has at least about 80% sequence identity; (iv) _VH comprising the amino acid sequence SEQ ID NO:59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:59 and V _L , which comprises the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; (v) V _H , which comprises the amino acid Sequence SEQ ID NO: 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 60; and V _L comprising the amino acid sequence SEQ ID NO: 77 or a variant thereof, The variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77; (vi) V _H comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof, said variant having the amino acid sequence of SEQ ID NO:61 has at least about 80% sequence identity; and _VL , it comprises amino acid sequence SEQ ID NO:77 or its variant, and said variant has at least about 80% sequence identity with amino acid sequence SEQ ID NO:77 (vii) V _H , which comprises the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 57; and V _L , which comprises the amino acid sequence SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; (viii) V _H comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof , the variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:58; and V _L comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof, said variant having the amino acid sequence of SEQ ID NO 78 has at least about 80% sequence identity; (ix) V _H , which comprises the amino acid sequence SEQ ID NO: 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 59 and V _L , which comprises the amino acid sequence of SEQ ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78; (x) V _H , which comprises the amino acid Sequence SEQ ID NO: 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 60; and _VL comprising the amino acid sequence SEQ ID NO: 78 or a variant thereof, The variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78; (xi) V _H comprising the amino acid sequence of SEQ ID NO:61 or a variant thereof which is identical to the amino acid sequence of SEQ ID NO:61 has at least about 80% sequence identity; and _VL , it comprises amino acid sequence SEQ ID NO:78 or its variant, and said variant has at least about 80% sequence identity with amino acid sequence SEQ ID NO:78 (xii) V _H comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 57; and V _L comprising the amino acid sequence SEQ ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; (xiii) V _H comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof , the variant having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:58; and V _L comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof, said variant having the amino acid sequence of SEQ ID NO :79 has at least about 80% sequence identity; (xiv) V _H comprising the amino acid sequence SEQ ID NO:59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:59 and V _L , which comprises the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; (xv) V _H , which comprises the amino acid Sequence SEQ ID NO: 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO: 60; and _VL comprising the amino acid sequence SEQ ID NO: 79 or a variant thereof, Said variant has at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; or (xvi) V _H comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof which is identical to the amino acid sequence of SEQ ID NO: 79 ID NO:61 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79 sex.

In some embodiments, the isolated anti-MASP2 antibody binds human MASP2 with a Kd value of 1 pM to 10 nM.

In some embodiments, an isolated anti-MASP2 antibody is provided that competes with any of the isolated anti-MASP2 antibodies described above for specific binding to MASP2. In some embodiments, an isolated anti-MASP2 antibody is provided that specifically binds to the same epitope as any of the isolated anti-MASP2 antibodies described above.

In some embodiments, any of the isolated anti-MASP2 antibodies described above, the isolated anti-MASP2 antibody comprising an Fc fragment. In some embodiments, the isolated anti-MASP2 antibody is a full length IgG antibody. In some embodiments, the isolated anti-MASP2 antibody is a full length IgGl or IgG4 antibody. In some embodiments, the isolated anti-MASP2 antibody is a chimeric, fully human or humanized antibody. In some embodiments, the isolated anti-MASP2 antibody is an antigen-binding fragment selected from the group consisting of Fab, Fab', F(ab)' ₂ , Fab'-SH, single chain Fv (scFv), Fv In the group consisting of fragment, dAb, Fd, nanobody (nanobody), double-chain antibody (diabody) and linear antibody.

In some embodiments, an isolated nucleic acid molecule encoding any of the anti-MASP2 antibodies described above is provided. In some embodiments, there is provided a vector comprising any one of the nucleic acid molecules described above. In some embodiments, there is provided a host cell comprising any of the above-mentioned anti-MASP2 antibodies, any of the above-mentioned nucleic acid molecules, or any of the above-mentioned vectors. In some embodiments, there is provided a method for preparing an anti-MASP2 antibody, comprising: a) cultivating any one of the above-mentioned host cells under conditions capable of effectively expressing an anti-MASP2 antibody; and b) obtaining the expressed anti-MASP2 antibody from the host cell MASP2 antibody.

In some embodiments, there is provided a method of treating a disease or condition in an individual in need thereof, comprising administering to said individual an effective amount of any one of the anti-MASP2 antibodies described above. In some embodiments, there is provided use of any one of the anti-MASP2 antibodies described above for the manufacture of a pharmaceutical composition for treating a disease or condition in an individual in need thereof. In some embodiments, use of any anti-MASP2 antibody or a pharmaceutical composition comprising an anti-MASP2 antibody as described above in the preparation of a medicament for treating a disease or disorder is provided. In some embodiments, the disease or disorder is associated with MASP2-dependent complement activation, including autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and/or viral infectious disease disease or disease. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation (TA-TMA), Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), disseminated intravascular coagulation (DIC), angiogenesis-dependent cancers, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neogenesis Vascular, retinopathy of prematurity, and respiratory distress syndrome or pneumonia caused by coronavirus infection, etc.

Also provided are pharmaceutical compositions, kits, and articles of manufacture comprising any of the anti-MASP2 antibodies described above.

Description of drawings

The results shown in Figure 1 are the activity of anti-MASP2 antibodies humM2mc51-1 and humM2mc67-9 in inhibiting C4b deposition in monkey serum.

The results shown in Fig. 2 are the trends of plasma drug concentration of anti-MASP2 antibodies humM2mc12-1, humM2mc51-1, humM2mc67-9 over time.

The results shown in Figures 3A-3C show that the anti-MASP2 antibodies humM2mc67 and humM2mc51-1 inhibited the formation of C4b (Figure 3A), C3b (Figure 3B) and MAC (Figure 3C) in cynomolgus monkeys.

Detailed description of the application

In one aspect the application provides anti-MASP2 antibody molecules. Through a combination of scFv phage library screening, appropriately designed biochemical and biological experiments, and antibody humanization, highly potent antibody molecules capable of binding human MASP2 and inhibiting activation of the MASP2-dependent complement lectin pathway have been identified. The results presented herein demonstrate that the antibodies of the present application are more effective at inhibiting complement lectin pathway activation than known anti-MASP2 antibodies.

Anti-MASP2 antibodies provided by the application include, for example, full-length anti-MASP2 antibodies, anti-MASP2 single-chain antibodies (scFvs), anti-MASP2 Fc fusion proteins, multispecific (such as bispecific) anti-MASP2 antibodies, anti-MASP2 immunoconjugates joints and whatnot.

In another aspect, the application provides an anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), the V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SDYAWN (SEQ ID NO:1); HC-CDR2, it comprises YISYSGRTSYNPSLKS (SEQ ID NO:5); And HC-CDR3, it comprises HYGX ₁ X ₂ (SEQ ID NO:38), wherein X ₁ is D or S, X ₂ is H or Y; and a light chain variable domain (V _L ), said V _L comprising: a light chain complementarity determining region (LC-CDR) 1 comprising KASQNVGTNVA (SEQ ID NO: 19); LC- CDR2 comprising SASYRYS (SEQ ID NO:26); and LC-CDR3 comprising X ₁ QYNSX ₂ X ₃ X ₄ (SEQ ID NO:39), wherein X ₁ is H or Q, X ₂ is N or Y , X ₃ is L or P, X ₄ is L or T.

In another aspect, the application provides an anti-MASP2 antibody, the anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), the V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SFWMH (SEQ ID NO:2); HC-CDR2 comprising YINPGTGYTDYNQKFKD (SEQ ID NO:6); and HC-CDR3 comprising FYGRRGY (SEQ ID NO:15); and light chain variable domain (V _L ) , the V _L comprises: light chain complementarity determining region (LC-CDR) 1, which comprises SASSSVSYMH (SEQ ID NO: 20); LC-CDR2, which comprises STSNLAS (SEQ ID NO: 27); and LC-CDR3, It comprises QQRSSYPFT (SEQ ID NO: 32).

In another aspect, the application provides an anti-MASP2 antibody, the anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), the V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SFWMH (SEQ ID NO:2); HC-CDR2, which comprises YINPSTGYTDYNQQFKD (SEQ ID NO:7); and HC-CDR3, which comprises FYGRRDY (SEQ ID NO:16); and a light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising SASSSVSSMH (SEQ ID NO:21); LC-CDR2 comprising STSNLAS (SEQ ID NO:27); and LC-CDR3, It comprises QQRSNYPFT (SEQ ID NO: 33).

In another aspect, the application provides an anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), the V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SDYAWN (SEQ ID NO:1); HC-CDR2, which comprises YISYSGRTSYNPSLKS (SEQ ID NO:5); and HC-CDR3, which comprises IGTLGY (SEQ ID NO:17); and a light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising KASQNVGTNVA (SEQ ID NO: 19); LC-CDR2 comprising SASYRYS (SEQ ID NO: 26); and LC-CDR3, It comprises HQYNSNPLT (SEQ ID NO:31).

In another aspect, the application provides an anti-MASP2 antibody, said anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), said V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising RFGMH (SEQ ID NO:3); HC-CDR2, which comprises YISSGGSAIFYADTVKG (SEQ ID NO:8); and HC-CDR3, which comprises GDRALDY (SEQ ID NO:18); and a light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising RASQSVSSSSYSYIH (SEQ ID NO:22); LC-CDR2 comprising HASNLES (SEQ ID NO:28); and LC-CDR3, It comprises QHSWESPWT (SEQ ID NO:34).

In another aspect, the application provides an anti-MASP2 antibody, said anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), said V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising RFGMH (SEQ ID NO:3); HC-CDR2, which comprises YISSGGSSIFYADTVKG (SEQ ID NO:9); and HC-CDR3, which comprises GDRALDY (SEQ ID NO:18); and light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising RASKSVSTSGYSYIH (SEQ ID NO:23); LC-CDR2 comprising YASNLES (SEQ ID NO:29); and LC-CDR3, It comprises QHSWEAPWT (SEQ ID NO: 35).

In another aspect, the application provides an anti-MASP2 antibody, said anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), said V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising RFGMH (SEQ ID NO:3); HC-CDR2, which comprises YISSGSSAVFYADTVKG (SEQ ID NO:10); and HC-CDR3, which comprises GDRALDY (SEQ ID NO:18); and light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising RASQSVSSSSYSYIH (SEQ ID NO:22); LC-CDR2 comprising HASNLES (SEQ ID NO:28); and LC-CDR3, It comprises QHSWESPWT (SEQ ID NO:34).

In another aspect, the application provides an anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), the V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SFGMH (SEQ ID NO:4); HC-CDR2, which comprises YISSGSRSVFYADTVKG (SEQ ID NO:11); and HC-CDR3, which comprises GDRALDY (SEQ ID NO:18); and a light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising RASQSVSSSSYGYIH (SEQ ID NO:24); LC-CDR2 comprising HASNLES (SEQ ID NO:28); and LC-CDR3, It comprises QHSWESPWT (SEQ ID NO:34).

In another aspect, the application provides an anti-MASP2 antibody, said anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), said V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising RFGMH (SEQ ID NO:3); HC-CDR2, which comprises YISSGSSSIFYADTVKG (SEQ ID NO:12); and HC-CDR3, which comprises GDRALDY (SEQ ID NO:18); and light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising RASKSVSTSGYSYIH (SEQ ID NO:23); LC-CDR2 comprising HASNLES (SEQ ID NO:28); and LC-CDR3, It comprises LHSWESPWT (SEQ ID NO:36).

In another aspect, the application provides an anti-MASP2 antibody, said anti-MASP2 antibody comprising: a heavy chain variable domain (V _H ), said V _H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising RFGMH (SEQ ID NO:3); HC-CDR2, which comprises YISSGSSAVFYADTVKG (SEQ ID NO:10); and HC-CDR3, which comprises GDRALDY (SEQ ID NO:18); and light chain variable domain (V _L ) , the _VL comprising: light chain complementarity determining region (LC-CDR) 1 comprising RASQSVSSSRYSYIH (SEQ ID NO:25); LC-CDR2 comprising HASNLES (SEQ ID NO:28); and LC-CDR3, It comprises QHSWDTPWT (SEQ ID NO: 37).

Also provided are nucleic acids encoding anti-MASP2 antibodies, compositions comprising anti-MASP2 antibodies, and methods for preparing and using anti-MASP2 antibodies.

definition

As used herein, "treatment" or "treating" is a method of obtaining a beneficial or desired result, including a clinical result. For the purposes of this application, the beneficial or desired clinical result, Including, but not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, reducing the extent of the disease, stabilizing the disease (for example, preventing or delaying disease progression), preventing or delaying the spread of the disease (for example, metastasis) , preventing or delaying disease recurrence, delaying or slowing disease progression, improving disease state, remission of disease (partial or total), reducing dose of one or more other drugs needed to treat disease, delaying disease progression, improving or enhancing quality of life , increase body weight, and/or prolong survival. Meanwhile, "treatment" also includes the reduction of disease pathological outcome (for example, immune complex deposition reduces, inhibits thrombus formation). The method of the present application considers any one or more of these treatments aspect.

The term "antibody" includes full-length antibodies and antigen-binding fragments thereof. Full-length antibodies include two heavy chains and two light chains. The variable regions of the light and heavy chains are responsible for antigen binding. The variable regions in both chains usually include 3 hypervariable loops called complementarity determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2 and LC-CDR3, heavy chain (HC ) CDRs include HC-CDR1, HC-CDR2 and HC-CDR3). The CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified by the Kabat, Chothia or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). The three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more conserved than the CDR regions and form a scaffold to support the hypervariable loops. The constant regions of the heavy and light chains are not involved in antigen binding, but exhibit various effector functions. Antibodies are classified based on the amino acid sequence of the constant region of their heavy chains. The five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG and IgM, characterized by heavy chains of the alpha, delta, epsilon, gamma and mu types, respectively. Several major antibody classes are divided into subclasses such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain) or IgA2 ( α2 heavy chain).

As used herein, the term "antigen-binding fragment" includes antibody fragments, for example, diabodies, Fab, Fab', F(ab') ₂ , Fv fragments, disulfide bond-stabilized Fv fragments (dsFv), (dsFv) ₂ , bispecific dsFv (dsFv-dsFv'), disulfide bond stabilized diabody (ds diabody), single chain Fv (scFv), scFv dimer (divalent diabody), Multispecific antibodies, single domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragments that are capable of binding to an antigen but do not contain the complete antibody structure, consisting of antibody fragments containing one or more CDRs . An antigen-binding fragment is capable of binding the same antigen as a parent antibody or a fragment of a parent antibody (eg, a parent scFv). Antigen-binding fragments also include fusion proteins comprising the antibody fragments described above. In some embodiments, an antigen-binding fragment may comprise one or more CDRs from a particular human antibody grafted into framework regions from one or more different human antibodies.

As used herein, the term "epitope" refers to a specific atom or group of amino acids on an antigen to which an antibody or antibody portion binds. If two antibodies or antibody portions appear to compete for binding to an antigen, they likely bind the same epitope on the antigen.

As used herein, when the first antibody inhibits the binding of the second antibody to the MASP2 target by at least 50% (eg, at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%) at an equimolar concentration , 95%, 98%, or 99%), the primary antibody "competes" with the secondary antibody for binding to the MASP2 target, and vice versa. PCT publication WO 03/48731 describes a cross-competition-based high-throughput antibody "epitope-sorting" method.

As used herein, the term "specifically binds", "specifically recognizes" or "is specific for" refers to a measurable and reproducible interaction, for example binding of an antibody to a target can The presence of the target is determined in a heterogeneous population of molecules, including biomolecules. For example, the ability of an antibody to specifically recognize a certain target (which may be an epitope) means that the antibody binds to the target with higher affinity, avidity, easier and/or longer duration than other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more epitopes of the antigen with a binding affinity at least 10 times greater than its binding affinity for other targets.

As used herein, an "isolated" anti-MASP2 antibody refers to an anti-MASP2 antibody that is (1) not related to the naturally occurring protein, (2) free of other proteins of the same origin, (3) produced from a different species expressed by cells of the genus, or (4) does not exist in nature.

As used herein, the term "isolated nucleic acid" refers to nucleic acid of genomic, cDNA or synthetic origin or combinations thereof. According to its source, the "isolated nucleic acid" refers to (1) not related to all or part of the polynucleotide in the "isolated nucleic acid" found in nature, (2) may be associated with polynucleotides that are not associated with it in nature. The nucleotides are operably linked, or (3) do not occur in nature as part of a longer sequence.

As used herein, the term "CDR" or "complementarity determining region" means the non-contiguous antigen binding sites found within the variable domains of heavy and light chain polypeptides. In the literature Kabat et al., J.Biol.Chem.252:6609-6616 (1977); Kabat et al., U.S. Dept. of Health and Human Services, "Sequences of proteins of immunological interest" (1991); Chothia et al. al., J. Mol. Biol. 196:901-917 (1987); Al-Lazikani B. et al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J. Mol.Biol.262:732-745 (1996); Abhinandan and Martin, Mol.Immunol., 45:3832-3839 (2008); Lefranc M.P.et al., Dev.Comp.Immunol., 27:55-77( 2003); and Honegger and Plückthun, J.Mol.Biol., 309:657-670 (2001), where these definitions include overlaps or subunits of amino acid residues when compared to each other. set. However, any definition used to indicate the CDR of an antibody or grafted antibody or variant thereof is included within the scope of the terms defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the above cited references for comparison. Algorithms and binding interfaces for CDR prediction are known in the art, including, for example, Abhinandan and Martin, Mol. Immunol., 45:3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38: D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43:D432-D438 (2015). The contents of the references cited in this paragraph are hereby incorporated by reference in their entireties for this application and any claim(s) that may be incorporated herein.

Table 1: CDR Definitions

the	Kabat ¹ Kabat ¹	Chothia ² Chothia ²	MacCallum ³ MacCallum ³	IMGT ⁴ IMGT ⁴	AHo ⁵ AHo ⁵
V _H CDR1 V _H CDR1	31-3531-35	26-3226-32	30-3530-35	27-3827-38	25-4025-40
V _H CDR2 V _H CDR2	50-6550-65	53-5553-55	47-5847-58	56-6556-65	58-7758-77
V _H CDR3 V _H CDR3	95-10295-102	96-10196-101	93-10193-101	105-117105-117	109-137109-137
V _L CDR1 V _L CDR1	24-3424-34	26-3226-32	30-3630-36	27-3827-38	25-4025-40
V _L CDR2 V _L CDR2	50-5650-56	50-5250-52	46-5546-55	56-6556-65	58-7758-77
V _L CDR3 V _L CDR3	89-9789-97	91-9691-96	89-9689-96	105-117105-117	109-137109-137

¹ The numbering of amino acid residues refers to the naming method in Kabat et al.

² The numbering of amino acid residues refers to the naming method in Chothia et al.

³ The numbering of amino acid residues refers to the nomenclature in MacCallum et al.

⁴ The numbering of amino acid residues refers to the nomenclature in the above-mentioned Lefranc et al.

⁵ The numbering of amino acid residues refers to the nomenclature in Honegger and Plückthun mentioned above

The term "chimeric antibody" means that a part of the heavy chain and/or light chain is identical or homologous to the corresponding sequence in an antibody from a specific species or belonging to a specific antibody class or subclass, and this (s) chain The remaining part is identical or homologous to the corresponding sequence in antibodies from another genus or belonging to other antibody classes or subclasses, and fragments of such antibodies, as long as they have the biological activity in this application ( See U.S. Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).

"Fv" is the smallest antibody fragment that contains the complete antigen recognition and binding site. This fragment is a dimer formed by tight non-covalent linkage of one heavy chain variable domain and one light chain variable domain. Six hypervariable loops (3 loops each in the light and heavy chains) are derived from the folding of these two domains, which provide the antibody with amino acid residues for binding to the antigen and endow the antibody with the antigen binding specificity. However, even a single variable domain (or half of an Fv fragment, which contains only the 3 CDRs specific for an antigen) has the ability to recognize and bind antigen, albeit with a lower affinity than the full binding site.

"Single-chain Fv", also abbreviated "sFv" or "scFv", is an antibody fragment comprising the _VH and _VL antibody domains linked into a single polypeptide chain. In some embodiments, the scFv polypeptide further includes a linking polypeptide between the _VH and VL _domains , which allows the scFv to form a desired structure for antigen binding. For an overview of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

The term "diabody" is a small antibody fragment prepared by constructing a scFv fragment (see the above paragraph) using a short linker (for example, 5-10 residues) between the _VH and _VL domains. This allows for interchain rather than intrachain pairing of the variable domains, resulting in a bivalent fragment, ie, a fragment with two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" scFv fragments in which the _VH and _VL domains of the two antibodies are located on different polypeptide chains. Diabodies are fully described in EP 404,097; WO 93/11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

"Humanized" forms of non-human (eg, rodent) antibodies are chimeric antibodies, which include minimal sequence derived from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (recipient antibodies) in which the hypervariable region (HVR) residues of the recipient antibody are derived from non-human species such as mouse, rat, rabbit or Non-human mammalian hypervariable region residues with desired antibody specificity, affinity and performance are substituted (donor antibody). In some instances, residues in the framework regions of the human immunoglobulin are replaced by corresponding non-human residues. Additionally, humanized antibodies can include residues that are found neither in the recipient antibody nor in the donor antibody. These modifications can further improve antibody performance. Typically, a humanized antibody will comprise substantially all, at least one, and usually two variable domains in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin, and all or Essentially all framework regions are human immunoglobulin sequences. The human antibody optionally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For details, refer to Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992).

"Percent amino acid sequence identity (%)" or "homology" of the polypeptide and antibody sequences identified herein is defined: a sequence comparison is made where conservative substitutions are considered to be part of the sequence identity, and the candidate sequence is Compare the percentage of identical amino acid residues in polypeptide sequences. Percent amino acid sequence identity can be determined by various alignment methods that are within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. However, for the purposes herein, percent amino acid sequence identity values are calculated using the sequence alignment computer program MUSCLE (Edgar, R.C., Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, R.C., BMC Bioinformatics 5(1) :113,2004) generated.

The term "Fc receptor" or "FcR" is used to describe a receptor that binds the Fc region of an antibody. In some embodiments, the FcR described herein is an FcR that binds an IgG antibody (a gamma receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants of these receptors and available into spliced form. FcyRII receptors include FcyRIIA ("activating receptor") and FcyRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in the cytoplasmic domain. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine inhibition motif (ITIM) (see M.in

Annu. Rev. Immunol. 15:203-234 (1997)). The term also includes allotypes, eg FcyRIIIA allotypes: FcyRIIIA-Phe158, FcyRIIIA-Val158, FcyRIIA-R131 and/or FcyRIIA-H131. In Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J.Lab.Clin.Med.126 FcRs are described in: 330-41 (1995). The term FcR in this application encompasses other types of FcRs, including FcRs identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the neonate (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994 )).

The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC) and consists of an alpha chain non-covalently bound to beta2 microglobulin. The diverse functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from mother to neonate and in the regulation of serum IgG levels. FcRn acts as a salvage receptor that binds and transports endocytosed IgG in intact form within and between cells and saves them from undergoing the default degradation pathway.

The "CH1 domain" of the human IgG heavy chain constant region typically extends from amino acid 118 to amino acid 215 (EU numbering system).

A "hinge region" is generally defined as extending from Glu 216 to Pro 230 of human IgGl (Burton, Molec. Immunol. 22:161-206 (1985)). Hinge regions of other IgG isotypes can be aligned with the IgGl sequence by placing the first and last cysteine residues that form inter-heavy chain disulfide bonds in the same position as IgGl.

The "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340. The CH2 domain is unique in that it is not tightly paired with another region, but instead has two N-terminally linked branched sugar chains inserted between the two CH2 domains of the intact native IgG molecule. It has been speculated that sugars may act as a surrogate for domain-to-domain pairing, helping to keep the CH2 domain stable. Burton, Molec. Immunol. 22:161-206 (1985).

A "CH3" domain includes a stretch within the Fc region from the C-terminal residue to the CH2 domain (from amino acid 341 to the C-terminus of the antibody sequence, usually amino acid residue 446 or 447 of IgG).

A "functional Fc fragment" has the "effector function" that a native Fc region sequence has. Exemplary "effector functions" include Clq binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; Such as B cell receptor; BCR) and so on. Such effector functions typically require binding of the Fc region to a binding domain (eg, antibody variable region) and can be assessed using a variety of assays well known in the art.

Antibodies of IgG Fc variants having "altered" FcR binding affinity or ADCC activity have increased or decreased FcR binding activity and/or ADCC activity compared to a parent polypeptide or a polypeptide comprising a native Fc sequence. An Fc variant exhibiting "enhanced binding" to an FcR has a higher binding affinity for at least one FcR (e.g., a lower apparent Kd or _IC50 value) than the parental polypeptide or a polypeptide comprising a native IgG Fc sequence. ). In some embodiments, the binding ability is increased by 3 times, such as 5, 10, 25, 50, 60, 100, 150, 200, even up to 500 times or the binding ability is increased by 25% to 1000% compared with the parental polypeptide. An Fc variant that exhibits "reduced binding" to an FcR has a lower affinity for at least one FcR (eg, a higher apparent Kd or _IC50 value) than a parental polypeptide. The binding ability is reduced by 40% or more compared to the parental polypeptide.

"Antibody-dependent cell-mediated cytotoxicity" or "ADCC" is a form of cytotoxicity in which secreted Ig interacts with cells present in certain cytotoxic cells such as natural killer cells (NK), neutrophils, Binding to Fc receptors (FcRs) on macrophages enables these cytotoxic effector cells to specifically bind to target cells bearing antigens and subsequently kill target cells with cytotoxins. Antibodies "arm" the cytotoxic cells and are required for this killing. Among the main cell types that mediate ADCC, NK cells only express FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). To assess the ADCC activity of a molecule of interest, an in vitro ADCC assay can be performed, as described in US Patent No. 5,500,362 or 5,821,337. Suitable effector cells for such experiments include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK). Alternatively, or in addition, the ADCC activity of a molecule of interest can also be assessed in vivo, for example as described in animal models as disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).

A polypeptide comprising an Fc region variant that exhibits "enhanced ADCC activity" or is capable of mediating ADCC effects more efficiently in the presence of human effector cells compared to a wild-type IgG Fc polypeptide or a parental polypeptide comprising a variant Fc region When the polypeptide of the antibody is substantially the same in number as the wild-type IgG Fc polypeptide (or parental polypeptide) in the experiment, it can mediate ADCC more effectively in vitro or in vivo. Such variants are typically identified using any in vitro ADCC assay known in the art, eg, assays or methods for identifying ADCC activity, eg, in animal models and the like. In some embodiments, such variants mediate ADCC 5 to 100 fold more efficiently, eg 25 to 50 fold, compared to wild type Fc (or parental polypeptide).

"Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (Clq) to antibodies (subclasses of appropriate structure) that bind cognate antigens. To assess complement activation, a CDC assay can be performed as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996). Polypeptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding ability are described in US Patent No. 6,194,551B1 and WO99/51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).

Unless otherwise stated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are mutually degenerate forms and encode the same amino acid sequence. A nucleotide sequence encoding a protein or RNA may also include introns, eg, a nucleotide sequence encoding a protein may, in some forms, include introns.

The term "operably linked" refers to a functional linkage between a regulatory sequence and a heterologous nucleotide sequence such that the latter is expressed. For example, a first nucleotide sequence is operably linked to a second nucleotide sequence when the first nucleotide sequence is in a functional relationship with the second nucleotide sequence. For example, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Typically, operably linked DNA sequences are contiguous and, when necessary, join two protein coding regions in the same reading frame.

"Homologous" refers to sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same position in the two compared sequences is the same base or amino acid monomer subunit, for example, the same position in the two DNA molecules is adenine, then the two DNA molecules are homologous at this position. The percent homology between two sequences is a function of the ratio of the number of matching or homologous positions shared by the two sequences to the total number of positions multiplied by 100. For example, if 6 out of 10 positions in two sequences are matched or homologous, then the homology of the two sequences is 60%. For example, the DNA sequences ATTGCC and TATGGC share 50% homology. Generally speaking, when comparing two sequences, the comparison is performed with the aim of obtaining the maximum homology.

An "effective amount" of an anti-MASP2 antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose. An "effective amount" can be determined empirically and by methods known in relation to the purpose.

The term "therapeutically effective amount" refers to the amount of the anti-MASP2 antibody or composition thereof disclosed herein that can effectively treat the individual's disease or symptom. That is, an amount sufficient to reduce or improve the severity and/or duration of the disease or one or more symptoms thereof; prevent the development of the disease, cause the disease to regress, and prevent the recurrence, development, or onset of one or more symptoms associated with the disease or progression, detection of a disease, or an amount that enhances/improves the preventive or therapeutic effect of another therapy (eg, a prophylactic or therapeutic agent).

As used herein, "pharmaceutically acceptable" or "pharmacologically compatible" refers to a material that has no biological activity or other undesired properties, for example, the material can be added to a pharmaceutical composition administered to a patient, and Does not cause significant adverse biological reactions, or interact in a deleterious manner with any other components contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required criteria for toxicology or manufacturing testing and/or are included in the inactive ingredient guidelines prepared by the US Food and Drug Administration.

Embodiments of the application described herein are to be understood to include "consisting of" and/or "consisting essentially of" embodiments.

Reference herein to "about" as a value or parameter includes (and describes) variations to that value or parameter itself. For example, description referring to "about X" includes description of "X".

As used herein, reference to "not" a value or parameter generally means and describes "other than" a value or parameter. For example, the method cannot be used to treat type X cancer, meaning that the method is usually used to treat other types of cancer than type X cancer.

As used herein and in the appended claims, the singular forms "a", "an" and "the" include plural referents unless the context clearly dictates otherwise.

anti-MASP2 antibody

In one aspect, the application provides anti-MASP2 antibodies that specifically bind human, cynomolgus monkey and/or mouse MASP2. The anti-MASP2 antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy and/or light chain CDRs described herein. In one aspect, the application provides isolated antibodies that bind MASP2. Contemplated anti-MASP2 antibodies include, for example, full-length anti-MASP2 antibodies (e.g., full-length IgG1 or IgG4), anti-MASP2 single-chain antibodies, anti-MASP2 Fc fusion proteins, multispecific (e.g., bispecific) anti-MASP2 antibodies, anti-MASP2 Immunoconjugates, and whatnot. In some embodiments, the anti-MASP2 antibody is a full-length antibody (eg, full-length IgGl or IgG4) or an antigen-binding fragment thereof that specifically binds MASP2. In some embodiments, the anti-MASP2 antibody is Fab, Fab', F(ab)' ₂ , Fab'-SH, single chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody (diabody) or linear antibody. In some embodiments, an antibody that specifically binds to MASP2 refers to that the binding affinity of the antibody to MASP2 is at least 10 times that of the non-target binding affinity (including, for example, 10, 10 ² , 10 ³ , 10 ⁴ , 10 ⁵ , 10 ⁶ , or 10 ⁷ times). In some embodiments, non-target refers to an antigen other than MASP2. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis or radioimmunoprecipitation analysis (RIA). Kd values can be determined by methods known in the art, such as surface plasmon resonance (SPR) techniques or biolayer interferometry (BLI).

Although anti-MASP2 antibodies comprising human sequences (eg, human heavy and light chain variable domains comprising human CDR sequences) are broadly discussed herein, non-human anti-MASP2 antibodies are also contemplated. In some embodiments, the non-human anti-MASP2 antibody comprises the human CDR sequences and non-human framework region sequences of the anti-MASP2 antibodies described herein, and in some embodiments, the non-human framework region sequences comprise any of the human CDR sequences for use as described herein. One or more of the human CDR sequences described above generate heavy and/or light chain variable domain sequences, including, for example, mammalian, e.g., mouse, rat, rabbit, pig, bovine (e.g., cow, bull, buffalo ), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (eg, lesser apes, macaques), etc. In some embodiments, non-human anti-MASP2 antibodies include anti-MASP2 antibodies produced by grafting one or more human CDR sequences described herein into non-human framework regions (eg, murine or chicken framework region sequences).

The complete amino acid sequence of an exemplary human MASP2 comprises or consists of the amino acid sequence shown in SEQ ID NO: 84. Wherein the CCP1-CCP2-SP domain of human MASP2 comprises the amino acid sequence shown in SEQ ID NO: 85 or consists of the amino acid sequence shown in SEQ ID NO: 85. .

In some embodiments, an anti-MASP2 antibody described herein specifically recognizes an epitope in human MASP2. In some embodiments, the anti-MASP2 antibody cross-reacts with MASP2 from a species other than human. In other embodiments, the anti-MASP2 antibodies are fully specific for human MASP2 and do not cross-react with other non-human species.

In some embodiments, the anti-MASP2 antibody cross-reacts with at least one allelic variant of the MASP2 protein (or fragment thereof). In some embodiments, the allelic variant has at most 30 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10) compared to a naturally occurring MASP2 protein (or fragment thereof). , 15, 20, 25 or 30) amino acid substitutions (eg conservative substitutions). In some embodiments, the anti-MASP2 antibody does not cross-react with any allelic variant of the MASP2 protein (or fragment thereof).

In some embodiments, the anti-MASP2 antibody cross-reacts with at least one interspecies variant of the MASP2 protein. In some embodiments, for example, the MASP2 protein (or fragment thereof) is human MASP2, and the interspecies variant of the MASP2 protein (or fragment thereof) is a variant in cynomolgus monkeys. In some embodiments, the anti-MASP2 antibody does not cross-react with any interspecies variants of the MASP2 protein.

In some embodiments, any anti-MASP2 antibody described herein, said anti-MASP2 antibody comprising an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-MASP2 antibody comprises an IgG1 heavy chain constant region. In some embodiments, the anti-MASP2 antibody comprises an IgG2 heavy chain constant region. In some embodiments, the anti-MASP2 antibody comprises an IgG3 heavy chain constant region. In some embodiments, the anti-MASP2 antibody comprises an IgG4 heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 80. In some embodiments, the heavy chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 81. In some embodiments, the anti-MASP2 antibody comprises a kappa light chain constant region. In some embodiments, the light chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 82. In some embodiments, the anti-MASP2 antibody comprises a lambda light chain constant region. In some embodiments, the light chain constant region comprises (including consists of or consists essentially of) the amino acid sequence of SEQ ID NO: 83. In some embodiments, the anti-MASP2 antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.

In some embodiments, the anti-MASP2 antibody comprises a heavy chain variable domain ( _VH ), and the _VH comprises: a heavy chain complementarity determining region (HC-CDR) 1 comprising SDYAWN (SEQ ID NO: 1); HC-CDR2, which comprises YISYSGRTSYNPSLKS (SEQ ID NO:5); and HC-CDR3, which comprises HYGX ₁ X ₂ (SEQ ID NO: 38), wherein X ₁ is D or S, and X ₂ is H or Y; and a light chain variable domain (V _L ) comprising: light chain complementarity determining region (LC-CDR) 1 comprising KASQNVGTNVA (SEQ ID NO: 19 ₎ ; LC-CDR2 comprising SASYRYS (SEQ ID NO:26); and LC-CDR3, it comprises X ₁ QYNSX ₂ X ₃ X ₄ (SEQ ID NO:39), wherein X ₁ is H or Q, X ₂ is N or Y, X ₃ is L Or P, X ₄ is L or T.

In some embodiments, the anti-MASP2 antibody comprises _VH , and the _VH comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:1; HC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:5 and HC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 13-14 or a variant thereof comprising at most about 3 (eg 1, 2 or 3) Amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises _VH , and the _VH comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:5 The amino acid sequence shown, HC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:13-14.

In some embodiments, the anti-MASP2 antibody comprises a V _L comprising: LC- _CDR1 comprising the amino acid sequence shown in SEQ ID NO: 19; LC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 the amino acid sequence shown; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:30-31 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) Amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a V _L comprising: LC- _CDR1 comprising the amino acid sequence shown in SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 26 The amino acid sequence shown, LC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:30-31.

In some embodiments, the anti-MASP2 antibody comprises _VH , and the _VH comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:1; HC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:5 and HC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 13-14 or a variant thereof comprising at most about 3 (eg 1, 2 or 3) Amino acid substitution; and _VL , said _VL comprising: LC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:19; LC-CDR2 comprising the amino acid sequence shown in SEQ ID NO:26; and LC - a CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 30-31 or a variant thereof comprising a substitution of up to about 3 (eg 1 , 2 or 3) amino acids.

In some embodiments, the anti-MASP2 antibody comprises _VH , and the _VH comprises: HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence set forth in SEQ ID NO:5 The amino acid sequence shown, and HC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:13-14; And V _L , said V _L comprises: LC-CDR1, it comprises SEQ ID NO:19 The amino acid sequence shown in LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 26, and LC-CDR3, which includes the amino acid sequence shown in any of SEQ ID NOs: 30-31.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 13, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 26, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 30, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 13; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:30.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 14, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 26, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:31.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC- _CDR2 contained in the _VH as shown in the amino acid sequence shown in any one of SEQ ID NOs: 40 or 44 and HC-CDR3; and _VL , said _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence shown in any one of SEQ ID NOs:62 or 65.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 40; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:62.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 44; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:65.

In some embodiments, the anti-MASP2 antibody comprises: V _H , said V _H comprising the amino acid sequence shown in any one of SEQ ID NOs:40-47 or a variant thereof, said variant being identical to SEQ ID NOs: The amino acid sequences shown in any of 40-47 have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity; and _VL , the V _L comprises the amino acid sequence shown in any of SEQ ID NOs: 62-68 or a variant thereof, and the variant has at least about 80 amino acid sequences shown in any of SEQ ID NOs: 62-68 % (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In _some embodiments, the anti-MASP2 antibody comprises a _VH comprising the amino acid sequence shown in any one of SEQ ID NOs:40-47, and _a _VL comprising SEQ ID NOs:62 The amino acid sequence shown in any one of -68.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 40, or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO: 40 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 62 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:62. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:40, and _a _VL comprising the amino acid sequence of SEQ ID NO:62.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 41 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:63. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:41, and _a _VL comprising the amino acid sequence of SEQ ID NO:63.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 41 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:64. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:41, and _a _VL comprising the amino acid sequence of SEQ ID NO:64.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 42 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:63. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:42, and _a _VL comprising the amino acid sequence of SEQ ID NO:63.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 42 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:64. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:42, and _a _VL comprising the amino acid sequence of SEQ ID NO:64.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 43 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:63. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:43, and _a _VL comprising the amino acid sequence of SEQ ID NO:63.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 43 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:64. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:43, and _a _VL comprising the amino acid sequence of SEQ ID NO:64.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 44 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 44 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 65 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:65. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:44, and _a _VL comprising the amino acid sequence of SEQ ID NO:65.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45, or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 45 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:45, and _a _VL comprising the amino acid sequence of SEQ ID NO:66.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 46 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:46, and _a _VL comprising the amino acid sequence of SEQ ID NO:66.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 47 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 66 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:47, and _a _VL comprising the amino acid sequence of SEQ ID NO:66.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45, or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 45 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 67 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:45, and _a _VL comprising the amino acid sequence of SEQ ID NO:67.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 46 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 67 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:46, and _a _VL comprising the amino acid sequence of SEQ ID NO:67.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 47 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 67 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:47, and _a _VL comprising the amino acid sequence of SEQ ID NO:67.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45, or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 45 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:45, and _a _VL comprising the amino acid sequence of SEQ ID NO:68.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 46 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:46, and _a _VL comprising the amino acid sequence of SEQ ID NO:68.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 47 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 68 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:47, and _a _VL comprising the amino acid sequence of SEQ ID NO:68.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:6, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 15, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 27, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 32, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 15; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 20, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:32.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 48; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:69.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 48 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 69 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:69. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:48, and _a _VL comprising the amino acid sequence of SEQ ID NO:69.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:7, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 16, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 27, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 33, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 16; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:33.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 49; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:70.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 49 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:70. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:49, and _a _VL comprising the amino acid sequence of SEQ ID NO:70.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 17, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 26, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 17; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:31.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO:50; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:71.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof having at least about 80% identity with the amino acid sequence _of SEQ ID NO: 50 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 71 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:71. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:50, and _a _VL comprising the amino acid sequence of SEQ ID NO:71.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:34.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 51; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:72.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:51 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO:51 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:51, and _a _VL comprising the amino acid sequence of SEQ ID NO:72.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:9, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 29, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 35, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:35.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO:52; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:73.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 52 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 73 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:73. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:52, and _a _VL comprising the amino acid sequence of SEQ ID NO:73.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 22, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:34.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 53; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:72.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 53 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 72 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:72. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:53, and _a _VL comprising the amino acid sequence of SEQ ID NO:72.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 24, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:34.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO:54; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:74.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:54 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO:54 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 74 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:74. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:54, and _a _VL comprising the amino acid sequence of SEQ ID NO:74.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 36, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 23, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:36.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO: 55; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:75.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 55 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 75 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:75. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:55, and _a _VL comprising the amino acid sequence of SEQ ID NO:75.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, HC -CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant _of said _VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and _VL comprising: LC-CDR1, It comprises the amino acid sequence of SEQ ID NO: 25, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 37, or a variant of said V _L , whose LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising: HC- _CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18; and V _L comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:37.

In some embodiments, the anti-MASP2 antibody comprises a _VH comprising HC-CDR1, HC-CDR2, and HC-CDR3 comprised by the _VH as shown in the amino acid sequence of SEQ ID NO:56; and a _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the _VL as shown in the amino acid sequence of SEQ ID NO:76.

In some embodiments, the anti-MASP2 antibody comprises: V _H , the V _H comprising the amino acid sequence shown in any one of SEQ ID NOs: 56-61 or a variant thereof, and the variant is identical to SEQ ID NOs: The amino acid sequences shown in any of 56-61 have at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity; and _VL , the V _L comprises the amino acid sequence shown in any one of SEQ ID NOs:76-79 or a variant thereof, and the variant has at least about 80 of the amino acid sequence shown in any one of SEQ ID NOs:76-79 % (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity. In _some embodiments, the anti-MASP2 antibody comprises a _VH comprising the amino acid sequence shown in any one of SEQ ID NOs:56-61, and _a _VL comprising SEQ ID NOs:76 The amino acid sequence shown in any one of -79.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:56 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO:56 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 76 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:76. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:56, and _a _VL comprising the amino acid sequence of SEQ ID NO:76.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 57 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:57, and _a _VL comprising the amino acid sequence of SEQ ID NO:77.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:58 or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO:58 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:58, and _a _VL comprising the amino acid sequence of SEQ ID NO:77.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:59 or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO:59 (e.g. at least 80%, 85%, 90%, 95%, 96% _, 97%, 98% or 99%) sequence identity; and a V _L comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:59, and _a _VL comprising the amino acid sequence of SEQ ID NO:77.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO: 60 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:60, and _a _VL comprising the amino acid sequence of SEQ ID NO:77.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 61 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:61, and _a _VL comprising the amino acid sequence of SEQ ID NO:77.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% identity with the amino acid sequence _of SEQ ID NO: 57 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:57, and _a _VL comprising the amino acid sequence of SEQ ID NO:78.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:58 or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO:58 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:58, and _a _VL comprising the amino acid sequence of SEQ ID NO:78.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:59 or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO:59 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:59, and _a _VL comprising the amino acid sequence of SEQ ID NO:78.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO: 60 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:60, and _a _VL comprising the amino acid sequence of SEQ ID NO:78.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 61 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 78 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:61, and _a _VL comprising the amino acid sequence of SEQ ID NO:78.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 57 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:57, and _a _VL comprising the amino acid sequence of SEQ ID NO:79.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:58 or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO:58 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:58, and _a _VL comprising the amino acid sequence of SEQ ID NO:79.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO:59 or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO:59 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:59, and _a _VL comprising the amino acid sequence of SEQ ID NO:79.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant _thereof having at least about 80% the amino acid sequence of SEQ ID NO: 60 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:60, and _a _VL comprising the amino acid sequence of SEQ ID NO:79.

In some embodiments, the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant _thereof having at least about 80% identity with the amino acid sequence of SEQ ID NO: 61 (e.g. at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof A variant having at least about 80% (eg, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibody comprises _a _VH comprising the amino acid sequence of SEQ ID NO:61, and _a _VL comprising the amino acid sequence of SEQ ID NO:79.

In some embodiments, the amino acid substitutions described above are limited to the "exemplary substitutions" shown in Table 4 herein. In some embodiments, amino acid substitutions are limited to the "preferred substitutions" shown in Table 4 herein.

In some embodiments, functional epitopes can be resolved by combined alanine scanning methods. In the process, combinatorial alanine scanning techniques can be used to identify amino acids in MASP2 proteins that are essential for interaction with anti-MASP2 antibodies. In some embodiments, the epitope is conformational, and the crystal structure of an anti-MASP2 antibody bound to a MASP2 protein can be used to identify the epitope.

In some embodiments, the application provides antibodies that compete for binding to MASP2 with any of the anti-MASP2 antibodies described herein. In some embodiments, antibodies are provided that compete with any of the anti-MASP2 antibodies described herein for binding to an epitope on MASP2. In some embodiments, anti-MASP2 antibodies are provided that bind to the same epitope as an anti-MASP2 antibody molecule comprising a _VH and a _VL , wherein the _VH comprises amino acids set forth in any one of SEQ ID NOs: 40-61 sequence, and the V _L comprises the amino acid sequence shown in any of SEQ ID NOs:62-79. In some embodiments, an anti-MASP2 antibody is provided that competes for binding to MASP2 with an anti-MASP2 antibody comprising a _VH and a _VL , wherein the _VH comprises the amino acid sequence set forth in any one of SEQ ID NOs: 40-61 , and the V _L comprises the amino acid sequence shown in any one of SEQ ID NOs:62-79.

In some embodiments, competition assays can be used to identify monoclonal antibodies that compete with the anti-MASP2 antibodies described herein for binding to MASP2. Competition experiments can determine whether two antibodies bind to the same epitope by recognizing identical or spatially overlapping epitopes or by one antibody competitively inhibiting binding of the other antibody to the antigen. In certain embodiments, such competing antibodies bind to the same epitope as the antibodies described herein. Some exemplary competition assays include, but are not limited to, conventional assays as mentioned in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.). A detailed exemplary method for resolving the epitope bound by an antibody is described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, N.J.). In some embodiments, each antibody is said to bind the same epitope if it blocks 50% or more of the binding of the other antibody. In some embodiments, antibodies that compete with the anti-MASP2 antibodies described herein are chimeric, humanized, or fully human antibodies.

Exemplary anti-MASP2 antibody sequences are shown in Table 2 and Table 3, wherein the CDRs are numbered according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms for predicting the position of the CDRs and defining the antibody light and heavy chain variable regions, comprising the CDRs, _VH and/or _VL sequences of antibodies as described herein, but based on the predicted Algorithms other than the antibodies exemplified in the table below are also within the scope of this application.

Table 2 Exemplary anti-MASP2 antibody CDR sequences

Table 3 Exemplary Sequences

Lectin

Collagen lectins (mannose-binding lectin (MBL), collagen lectin-10 (CL-10), collagen lectin-11 (CL-11)), ficolin (ficolin 1 (Ficolin-1) ), ficolin 2 (Ficolin-1), ficolin 3 (Ficolin-1)) are collectively referred to as lectins.

Mannose-binding lectin (MBL), also known as mannan-binding lectin and mannose/mannan-binding protein (MBP), is a multimer of basic triplet subunits composed of identical polypeptide chains composition. Its molecule has four domains: a cysteine-rich domain at the N-terminus, a collagen-like domain, an α-helical neck region, and a carbohydrate recognition domain at the C-terminus (Thiel, Steffen, and Mihaela Gadjeva. Advances in experimental medicine and biology vol.653(2009):58-73).

MBL binds Ca2 ⁺ cations and recognizes residues of carbohydrates such as D-mannose (D-Man), N-acetyl-D-glucosamine (D-GlcNAc), or L-fucose (L-Fuc). This enables it to interact with many microbial polysaccharides or glycoconjugates, such as capsular polysaccharides, lipopolysaccharides, fungal mannan, etc. In addition, it binds phospholipids and nucleic acids. It should be emphasized that MBL can not only recognize a variety of pathogens, but also recognize aging fibroblasts (Tomaiuolo, Rossella et al. Aging cell vol.11,3(2012):394-400), late apoptotic and necrotic cells (Nauta, Alma J et al. "European journal of immunology vol.33,10(2003): 2853-63) and some cancer cells with abnormal glycosylated surface structure (Fujita, T et al. Japanese journal of cancer research : Gann vol. 86, 2 (1995): 187-92).

Collagen lectin-10 (CL-10, also known as human liver collagen lectin-1, CL-L1) and collagen lectin-11 (CL-11 or human kidney collagen lectin-1, CL-K1) are two other A collagen lectin capable of activating complement through the lectin pathway, they form hetero-oligomers and termed CL-LK (Henriksen, Maiken L et al. Journal of immunological methods vol.413(2014):25-31 ). Hansen et al. reported that CL-10 and CL-11 are widely distributed in tissues and highly expressed in endocrine/exocrine tissues and mucosa (Hansen, Soren W K et al. Frontiers in immunology vol.9 1757.31Jul.2018). In the presence of calcium ions, collagen lectin-11 can recognize carbohydrates such as D-mannose (D-Man), L-fucose (L-Fuc) and N-acetyl-D glucosamine (D-GlcNAc) compound ligand. Except for some Gram-negative and Gram-positive bacteria, fungi and influenza A virus (Hansen, Soren W K et al. Immunobiology vol.221,10(2016):1058-67.Ma, Ying Jie et al. Journal of innate immunity vol.5,3(2013):242-50) In addition to the ability to interact with the surface structure, it is also found that it can bind to DNA from various sources, and it is speculated that it helps to bind to apoptotic cells, Granulocyte extracellular traps and biofilm responses (Henriksen, Maiken L et al. Molecular immunology vol.56,4(2013):757-67). In addition, CL-11 is considered to be involved in complement-mediated ischemic injury by interacting with L-fucose at the site of ischemic stress (Farrar, Conrad A et al. The Journal of clinical investigation vol.126,5(2016) :1911-25; Nauser, Christopher L et al. Frontiers in immunology vol.9 2023.6Sep.2018).

CL-10 can recognize D-mannose (D-Man), N-acetyl-D-glucosamine (D-GlcNAc), D-galactose (D-Gal), D-fucose (D-Fuc) and L-fucose (L-Fuc). Although the microbe/abnormal self-structure targeted by this collagen lectin protein has not been determined, as a component of CL-LK hetero-oligomers, it may expand the range of their interactions and/or modify their affinities ( Hansen, Soren W K et al. "Frontiers in immunology vol.9 1757.31 Jul.2018).

Ficolins, like collagen lectin proteins, are oligomeric, collagen-associated pattern recognition molecules. Although their structure and activity are generally similar to collagen lectin proteins, they do not have the typical lectin (carbohydrate binding) domain, but instead have a fibrinogen-like domain at the C-terminus responsible for the interaction with the target structure. Ficolin binds acetyl (not hydroxyl, as typical for lectins) groups, but not necessarily in sugar residues (Thiel, Steffen. Molecular immunology vol. 44, 16(2007): 3875-88; Matsushita , Misao et al.Archivum immunologiae et therapyae experimentalis vol.61,4(2013):273-83).

Ficolin-1, also known as M-ficolin, can recognize N-acetyl-D-glucosamine (D-GlcNAc), N-acetyl-D-mannosamine (D-ManNAc), N-acetyl- Ligands such as D-galactosamine (D-GalNAc) and sialic acid. In addition to microbial surface structures (such as bacterial envelope polysaccharides), it also binds to mitochondria of damaged host cells and (by forming a complex with penetrin-3) apoptotic/necrotic cells, which is important for homeostasis. It should be emphasized that sialic acid-rich glycoproteins are frequently overexpressed on the surface of metastatic cancer cells (Brinkmann, Christel R et al. The Journal of biological chemistry vol. 288, 12(2013): 8016-8027; Ma, Ying Jie et al. Journal of immunology (Baltimore, Md.: 1950) vol. 191, 3 (2013): 1324-33).

In contrast to other ficolins, ficolin-2 (or L-ficolin) has four binding sites in its fibrinogen (FBG) domain, enabling it to recognize a wide range of ligands ( N-acetyl-D-glucosamine (D-GlcNAc), N-acetyl-D-galactosamine (D-GalNAc), N-acetyl-D-D-mannosamine (D-ManNAc), D-galactose (D -Gal) and non-sugar compounds such as N-acetylated cysteine or acetylcholine) (Garlatti, Virginie et al. The EMBO journal vol.26,2(2007):623-33). Among the microbial structures targeted by ficolin-2 are bacterial capsular polysaccharides, lipoteichoic acid, and fungal-derived 1,3-β-glucan. In addition, it recognizes elastin and DNA. Similar to ficolin-1, ficolin-2 may contribute to the clearance of late apoptotic cells (Kuraya, Mikio et al. Immunobiology vol.209,9(2005):689-97; Jensen, Maria Lund et al.Molecular immunology vol.44,5(2007):856-65), thereby maintaining tissue homeostasis.

Ficolin-3 (also known as H-ficolin or Hakata antigen), like other ficolins, can recognize acetylated sugars, as well as D-fucose, L-fucose and D-semi Lactose (Garlatti, Virginie et al. The EMBO journal vol.26,2(2007):623-33). Although it has the highest serum concentration (median of nearly 20 μg/mL in adults) among pattern recognition molecules involved in the lectin pathway, no microbial ligand has been identified. However, it has been shown to aid in the clearance of apoptotic cells and can interact with ovarian cancer cells. Recently, it has been shown that ficolin-3 and ficolin-2 may form heterogeneous complexes in blood: they may have additional biological relevance compared to their parental molecules (Jarlhelt, Ida et al. Journal of immunology (Baltimore, Md.: 1950) vol. 204, 7 (2020): 1919-1928).

MASPs

It was originally discovered that MASP family proteins can form complexes with mannose-binding lectin (MBL), hence the name MBL-associated serine proteases, but they were later found to interact with ficolin and also with collagen lectin-10 and Collagen lectin-11 interaction. In addition to proteolytic enzymes (MASP-1, MASP-2, MASP-3), this family also includes factors with no enzymatic activity (MAp19, MAp44) (Cedzynski, Maciej et al. Journal of biomedicine & biotechnology vol. 2012 (2012): 363246; Matsushita, Misao et al. Archivum immunologiae et therapyae experimentalis vol.61,4(2013):273-83).

In general, the MASP zymogen is a single polypeptide chain protein (such as the specific C1r and C1s proteins of the classical pathway), which consists of 6 domains: CUB1 (C1r/C1, sea urchin epidermis, bone morphogenic protein), EGF (epidermal growth factor), CUB2, CCP1 (complement control protein), CCP-2 and SP (serine protease, catalytic). Upon activation, the peptide bond between the CCP2 and SP domains is cleaved, resulting in a heavy and light chain linked by a disulfide bond. Among them, the CUB1-EGF-CUB2 fragment can dimerize the MASP molecule and form a complex with collagen lectin or ficolin (Kjaer,Troels R et al.Structure(London,England:1993)vol.23,2(2015 ):342-51).

MASP-1, MASP-3, and the enzymatically inactive MAp44 (MBL-associated protein, 44kDA, also known as MAP-1) are products of the MASP1/3 genes. MASP-1 can cleave C2, and the cleavage product binds to C4b (less efficiently), so it was originally thought to upregulate the activation of the lectin pathway. However, it has now been shown to play a key role in MASP-2 activation. Furthermore, it may contribute to coagulation cascade activation: fibrinogen, factor XIII, and thrombin-activated fibrinolysis inhibitor (TAFI) are its substrates. In addition, its thrombin-like activity cleaves protease-activated receptor-4, a mediator of inflammation and platelet activation. Dobo et al. demonstrated that high molecular weight kininogen is another substrate of MASP-1 (Dobó, József et al. PloS one vol.6,5(2011):e20036). This activity (similar to kinins) is able to activate the release of bradykinin, a highly pro-inflammatory mediator of the contact system. In addition, studies have found that MASP-1 contributes to pro-inflammatory activation of endothelial cells and increases endothelial cell permeability (Jani, Péter K et al. PloS one vol.9, 1e87104.29 Jan.2014; Debreczeni, Márta L et al. Frontiers in immunology vol.10 991.3 May.2019). It was recently reported that MASP-1 affects the transcription of alternative pathway factor D (Holers, V Michael et al. Frontiers in immunology vol.11 201.21 Feb.2020).

The first described physiological substrate of MASP-3 was insulin-like growth factor binding protein-5 (IGFPB-5). IGFPB-5 is a regulator of the activity of IGFs (factors affecting cell proliferation, differentiation, motility and survival). MASP-3 is thought to downregulate activation of the lectin pathway due to competition with MASP-2 for binding pattern recognition lectins. However, later reports indicated that the natural substrate of MASP-3 is the factor D precursor and thus it is directly involved in the activation of the alternative pathway (Pihl, Rasmus et al. Journal of immunology (Baltimore, Md.: 1950), ji1700518. 9 Aug. 2017; Hayashi, Manabu et al. Journal of immunology (Baltimore, Md.: 1950) vol. 203, 6(2019): 1411-1416).

MAp44 (or MAP-1)) has four common domains (CUB1, EGF, CUB2, CCP1) with MASP-1 and MASP-3. A specific exon of this protein encodes an additional 17 amino acid residues at the C-terminus. Its biological role is uncertain, but it has been suggested that it downregulates the activity of the lectin pathway by competing with MASPs for MBL binding. It has also been shown to contribute to the regulation of cardiac development (Mortensen, Simon A et al. "Journal of immunology (Baltimore, Md.: 1950) vol. 198, 8(2017): 3118-3126).

Both MASP-2 and the enzymatically inactive MAp19 (MBL-associated protein, 19 kDa or sMAP, small MBL-associated protein) are encoded by the MASP2 gene. MASP-2 is able to efficiently cleave C4 and C2 and is therefore a key enzyme for the activation of the lectin pathway. In addition, it can activate prothrombin and participate in the activation of coagulation system (Garred, Peter et al. Immunological reviews vol.274,1(2016):74-97). Although another substrate of MASP-2 is kininogen, its cleavage does not lead to the production of bradykinin (Dobó, József et al. PloS one vol.6,5(2011):e20036).

Like MASP-1, MASP-2 was recently reported to be involved in D factor transcriptional regulation. MAp19 consists of two MASP-2 first domains and an additional four amino acid residues at the C-terminus (encoded by map19-specific exons) (Garred, Peter et al. Immunological reviews vol.274,1(2016) :74-97).

Full-length anti-MASP2 antibody

In some embodiments, the anti-MASP2 antibody is a full length anti-MASP2 antibody. In some embodiments, the full length anti-MASP2 antibody is IgA, IgD, IgE, IgG or IgM. In some embodiments, the full-length anti-MASP2 antibody comprises an IgG constant region, such as the constant region of IgGl, IgG2, IgG3, IgG4, or variants thereof. In some embodiments, the full length anti-MASP2 antibody comprises a lambda light chain constant region. In some embodiments, the full length anti-MASP2 antibody comprises a kappa light chain constant region. In some embodiments, the full-length anti-MASP2 antibody is a full-length human anti-MASP2 antibody. In some embodiments, the full length anti-MASP2 antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-MASP2 antibody comprises an Fc sequence that has been altered or otherwise altered such that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity The effector function of action (CDC).

Thus, for example, in some embodiments, a full length anti-MASP2 antibody comprising an IgG1 constant region that specifically binds MASP2 is provided. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG2 constant region that specifically binds MASP2 is provided. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG3 constant region that specifically binds MASP2 is provided. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG4 constant region that specifically binds MASP2 is provided. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any one of SEQ ID NOs: 1-4 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; HC-CDR2, which Comprising the amino acid sequence shown in any one of SEQ ID NOs: 5-12 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising The amino acid sequence shown in any one of SEQ ID NOs: 13-18, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and b) light chain variable structure Domain, the light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any one of SEQ ID NOs:19-25 or its variant, and described variant comprises up to about 3 (such as 1 , 2 or 3) amino acid substitutions, LC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 26-29 or a variant thereof comprising up to about 3 (for example 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 30-37 or a variant thereof comprising at most about 3 (for example 1, 2 or 3) Amino acid substitutions. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG2 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any one of SEQ ID NOs: 1-4 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; HC-CDR2, which Comprising the amino acid sequence shown in any one of SEQ ID NOs: 5-12 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising The amino acid sequence shown in any one of SEQ ID NOs: 13-18, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and b) light chain variable structure Domain, the light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any one of SEQ ID NOs:19-25 or its variant, and described variant comprises up to about 3 (such as 1 , 2 or 3) amino acid substitutions; LC-CDR2 comprising the amino acid sequence shown in any of SEQ ID NOs: 26-29 or a variant thereof comprising up to about 3 (eg 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 30-37 or a variant thereof comprising at most about 3 (for example 1, 2 or 3) Amino acid substitutions. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG3 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any one of SEQ ID NOs: 1-4 or a variant thereof comprising a substitution of at most about 3 (eg 1, 2 or 3) amino acids, HC-CDR2, which Comprising the amino acid sequence shown in any one of SEQ ID NOs: 5-12 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising The amino acid sequence shown in any one of SEQ ID NOs: 13-18, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and b) light chain variable structure Domain, the light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any one of SEQ ID NOs:19-25 or its variant, and described variant comprises up to about 3 (such as 1 , 2 or 3) amino acid substitutions; LC-CDR2 comprising the amino acid sequence shown in any of SEQ ID NOs: 26-29 or a variant thereof comprising up to about 3 (eg 1, 2 or 3) amino acid substitutions; and LC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 30-37 or a variant thereof comprising at most about 3 (for example 1, 2 or 3) Amino acid substitutions. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any one of SEQ ID NOs: 1-4 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; HC-CDR2, which Comprising the amino acid sequence shown in any one of SEQ ID NOs: 5-12 or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and HC-CDR3 comprising The amino acid sequence shown in any one of SEQ ID NOs: 13-18, or a variant thereof, said variant comprising at most about 3 (eg 1, 2 or 3) amino acid substitutions; and b) light chain variable structure Domain, the light chain variable domain comprises: LC-CDR1, it comprises the aminoacid sequence shown in any one of SEQ ID NOs:19-25 or its variant, and described variant comprises up to about 3 (such as 1 , 2 or 3) amino acid substitutions, LC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 26-29 or a variant thereof comprising up to about 3 (for example 1, 2 or 3) amino acid substitutions, and LC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 30-37 or a variant thereof comprising up to about 3 (eg 1, 2 or 3) Amino acid substitutions. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any of SEQ ID NOs:1-4, HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:5-12, and HC-CDR3, which comprises SEQ ID The amino acid sequence shown in any of NOs: 13-18, or a variant of the heavy chain variable domain, comprising at most about 5 (eg 1, 2, 3, 4 or 5) in its HC-CDR sequence ) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any of SEQ ID NOs: 19-25, LC-CDR2 , which comprises the amino acid sequence shown in any of SEQ ID NOs:26-29, and LC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:30-37, or the light chain variable structure A variant of a domain comprising up to about 5 (eg 1 , 2, 3, 4 or 5) amino acid substitutions in the LC-CDR sequence. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises a) a heavy chain variable domain comprising: HC-CDR1, It comprises the amino acid sequence shown in any one of SEQ ID NOs:1-4, HC-CDR2, it comprises the amino acid sequence shown in any one of SEQ ID NOs:5-12, and HC-CDR3, it comprises SEQ ID NOs : the amino acid sequence shown in any one of 13-18, or a variant of said heavy chain variable domain comprising at most about 5 (

eg

1, 2, 3, 4 or 5) in its HC-CDR sequence Amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence shown in any of SEQ ID NOs: 19-25, LC-CDR2, Comprising the amino acid sequence shown in any of SEQ ID NOs:26-29, and LC-CDR3, which includes the amino acid sequence shown in any of SEQ ID NOs:30-37, or the light chain variable domain A variant comprising up to about 5 (

eg

1 , 2, 3, 4 or 5) amino acid substitutions in the LC-CDR sequence. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any one of SEQ ID NOs:1-4, HC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:5-12, and HC-CDR3, which comprises SEQ ID The amino acid sequence shown in any of NOs:13-18; and b) the light chain variable domain comprising: LC-CDR1 comprising any of SEQ ID NOs:19-25 The amino acid sequence shown, LC-CDR2, it comprises the amino acid sequence shown in any one of SEQ ID NOs:26-29, and LC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:30-37 . In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence shown in any of SEQ ID NOs:1-4, HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:5-12, and HC-CDR3, which comprises SEQ ID The amino acid sequence shown in any of NOs:13-18; and b) the light chain variable domain comprising: LC-CDR1 comprising any of SEQ ID NOs:19-25 The amino acid sequence shown, LC-CDR2, it comprises the amino acid sequence shown in any one of SEQ ID NOs:26-29, and LC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:30-37 . In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:13; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :30. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 14; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :31. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:2, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:15; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 27, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :32. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:2, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:7, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:16; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:27, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :33. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 17; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :31. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:8, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :34. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:9, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :35. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:10, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :34. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 4, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 11, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :34. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:12, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :36. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:10, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 25, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :37. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:13; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :30. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 14; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :31. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:2, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:6, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:15; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO: 20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 27, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :32. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:2, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:7, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:16; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:21, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:27, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :33. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:1, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:5, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:17; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO :31. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:8, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :34. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:9, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :35. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:10, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :34. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO: 4, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 11, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :34. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:12, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :36. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full length anti-MASP2 antibody comprising an IgG4 constant region, wherein said anti-MASP2 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 , which comprises the amino acid sequence of SEQ ID NO:3, HC-CDR2, which comprises the amino acid sequence of SEQ ID NO:10, and HC-CDR3, which comprises the amino acid sequence of SEQ ID NO:18; and b) a light chain variable domain, The light chain variable domain comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:25, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO :37. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a heavy chain variable domain ( _VH ), said _VH comprising SEQ ID NOs: 40-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 40-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), said V _L comprising the amino acid sequence shown in any of SEQ ID NOs:62-79 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-79 , 98% or 99%) sequence identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG2 constant region is provided, wherein the anti-MASP2 antibody comprises: a heavy chain variable domain ( _VH ), said _VH comprising SEQ ID NOs: 40-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 40-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), said V _L comprising the amino acid sequence shown in any of SEQ ID NOs:62-79 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-79 , 98% or 99%) sequence identity. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG3 constant region is provided, wherein the anti-MASP2 antibody comprises: a heavy chain variable domain ( _VH ), said _VH comprising SEQ ID NOs: 40-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 40-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), said V _L comprising the amino acid sequence shown in any of SEQ ID NOs:62-79 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-79 , 98% or 99%) sequence identity. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a heavy chain variable domain ( _VH ), said _VH comprising SEQ ID NOs: 40-61 Any of the amino acid sequences shown, or variants thereof, which have at least about 80% (e.g., at least 80%, 85%, 90%, 95%) of any of the amino acid sequences shown in SEQ ID NOs: 40-61 %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), said V _L comprising the amino acid sequence shown in any of SEQ ID NOs:62-79 or a variant thereof having at least about 80% (eg at least 80%, 85%, 90%, 95%, 96%, 97%) of the amino acid sequence shown in any of SEQ ID NOs: 62-79 , 98% or 99%) sequence identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a heavy chain variable domain (V _H ), said (V _H ) comprising SEQ ID NOs: 40- The amino acid sequence shown in any one of 61, and the light chain variable domain (V _L ), said (V _L ) comprising the amino acid sequence shown in any one of SEQ ID NOs:62-79. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG4 constant region is provided, wherein the anti-MASP2 antibody comprises: a heavy chain variable domain ( _VH ), said _VH comprising SEQ ID NOs: 40-61 Any of the amino acid sequences shown, and a light chain variable domain (V _L ), said V _L comprising any of the amino acid sequences shown in SEQ ID NOs: 62-79. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 40 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:40 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:62 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 41 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 63 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 41 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 64 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO:42 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:63 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO:42 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:64 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO:43 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:63 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO:43 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:64 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 44 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:44 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:65 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:45 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:66 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:46 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:47 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:66 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:45 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:67 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:46 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:67 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:47 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:67 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:45 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:68 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:46 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:47 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:68 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:48 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:69 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO:49 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:70 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:50 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:71 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:72 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:73 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:73 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:53 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:72 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:54 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:74 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:55 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:75 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:75 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:56 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:76 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:76 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG1 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof, said variant being identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 40 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:40 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:62 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:62 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:41 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:63 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 41 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 64 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:42 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:63 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:42 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:64 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:43 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:63 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:43 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:64 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 44 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:44 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:65 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:45 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:66 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:46 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:47 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:45 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:67 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:46 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:67 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:47 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:67 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:45 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:68 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:46 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:47 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:68 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 48 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:48 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:69 or a variant thereof having at least about 80% sequence to the amino acid sequence of SEQ ID NO:69 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 49 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 49 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 70 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 50 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:50 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:71 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 51 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:51 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:72 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 52 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:52 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:73 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:73 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 53 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:53 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:72 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:72 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 54 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:54 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:74 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 55 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:55 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:75 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:75 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:56 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:76 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:76 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 59 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 77 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG4 constant region is provided, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:77 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a full-length anti-MASP2 antibody comprising an IgG4 constant region is provided, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:61 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:57 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:58 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:59 has at least about 80% sequence identity; and V _L , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof that is identical to the amino acid sequence SEQ ID NO:60 has at least about 80% sequence identity; and _VL , it comprises the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence with the amino acid sequence of SEQ ID NO:79 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, there is provided a full-length anti-MASP2 antibody comprising an IgG4 constant region, wherein the anti-MASP2 antibody comprises: _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof that is identical to the amino acid sequence SEQ ID NO: 61 has at least about 80% sequence identity; and V _L comprising the amino acid sequence of SEQ ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79 identity. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

binding affinity

Binding affinity is expressed as Kd, Koff, Kon or Ka. As used herein, the term Koff refers to the rate constant for dissociation of an antibody from an antigen/antibody complex, as determined by a kinetic selective device. The term Kon refers to the association rate constant for the binding of an antibody to an antigen to form an antigen/antibody complex. The equilibrium dissociation constant Kd used herein refers to the dissociation constant when a specific antibody-antigen interacts, and refers to the antigen concentration required when the antigen occupies half of all antibody binding sites and reaches equilibrium in the antibody molecule solution, which is equal to Koff /Kon. The determination of Kd assumes that all bound molecules are in solution. Where the antibody is attached to the cell wall, such as in a yeast expression system, the corresponding equilibrium dissociation rate constant is expressed in terms of EC50, which is a good approximation of Kd. The affinity association constant Ka is the reciprocal of the dissociation constant Kd.

The dissociation constant (Kd) can be used as an indicator of the affinity of the antibody moiety for the antigen. For example, simple analysis can be performed by the Scatchard method using antibodies labeled with various markers, and a Biacore instrument (manufactured by Amersham Biosciences), and the interaction between biomolecules can be analyzed by surface plasmon resonance according to the user's manual or the attached kit . Kd values obtained using these methods are expressed in units of M. An antibody that specifically binds a target may have, for example, ≤10 ⁻⁷ M, ≤10 ⁻⁸ M, ≤10 ⁻⁹ M, ≤10 ⁻¹⁰ M, ≤10 ⁻¹¹ M, ≤10 ⁻¹² M, or ≤10 ⁻ Kd value of ^13M .

The binding specificity of an antibody can be determined experimentally by methods known in the art. These methods include, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore tests, and peptide scans, among others.

In some embodiments, the anti-MASP2 antibody specifically binds a MASP2 target with a Kd value of 10 ⁻⁷ M to 10 ⁻¹³ M (e.g., 10 ⁻⁷ M to 10 ⁻¹³ M, 10 ⁻⁸ M to 10 ⁻¹³ M, 10 ^-9 M to 10 ^-13 M or 10 ^-10 M to 10 ^-12 M). Therefore, in some embodiments, the Kd value of the binding between the anti-MASP2 antibody and MASP2 is 10 ⁻⁷ M to 10 ⁻¹³ M, 1×10 ⁻⁷ M to 5× ^{10 −13} ^M , 10 ⁻⁷ M to 10 ^-12 M, 10 ^-7 M to 10 ^-11 M, 10 ^-7 M to 10 ^-10 M, 10 ^-7 M to 10 ^-9 M, 10 ^{-8 M to 10 -13} ^M , 1×10 ^-8 M to 5×10 ^-13 M, 10 ^-8 M to 10 ^-12 M, 10 ^-8 M to 10 ^-11 M, 10 ^-8 M to 10 ^-10 M, 10 ^-8 M to 10 ^-9 M, 5× ^10-9 M to 1× ^10-13 M, 5× ^10-9 M ^to 1× ^10-12 M, 5× ^10-9 M to 1×10-11 M, 5× ^10-9 M to 1×10 ^-10 M, 10 ^- ⁹ M to 10 ^-13 M, 10 ^-9 M to 10 ^-12 M, 10 ^-9 M to 10 ^-11 M, 10 ^-9 M to 10 ^-10 M, 5×10 ^-10 M to 1× ^10-13 M, 5× ^10-10 M to 1× ^10-12 M, 5× ^10-10 M to 1× ^10-11 M, ^10-10 M to ^10-13 M, 1× ^{10- 10} M to 5× ^10-13 M, 1× ^10-10 ^M to 1× ^10-12 M, 1× ^10-10 M to 5× ^10-12 M, 1× ^10-10 M to 1× ^10-11 M, 10 ^-11 M to 10 ^-13 M, 1×10 ^-11 M to 5×10 ^-13 M, 10 ^-11 M to 10 ^-12 M, 10 ^-12 M to 10 ^-13 M. In some embodiments, the Kd value of the binding between the anti-MASP2 antibody and MASP2 is 10 ⁻⁷ M to 10 ⁻¹³ M.

In some embodiments, the Kd value for the binding of the anti-MASP2 antibody to a non-target is higher than the Kd value for the binding of the anti-MASP2 antibody to the target, and in some embodiments cited herein, the Kd value for the binding of the anti-MASP2 antibody to the target (e.g., MASP2) The binding affinity is higher than the binding affinity of the anti-MASP2 antibody to non-targets. In some embodiments, non-target refers to an antigen other than MASP2. In some embodiments, the anti-MASP2 antibody (for MASP2) binds a non-MASP2 target with a Kd value that differs by at least 10-fold, for example, 10-100-fold, 100-1000-fold, ^103-104 ^- fold, ^104-105 ^-fold times, 10 ⁵ -10 ⁶ times, 10 ⁶ -10 ⁷ times, 10 ^{7 -10 8 times, 10 8} ^-10 ⁹ ^times , 10 ⁹ -10 ¹⁰ times, 10 ¹⁰ -10 ¹¹ times, 10 ¹¹ -10 ¹² times .

In some embodiments, the non-target binding Kd value of the anti-MASP2 antibody is 10 ⁻¹ M to 10 ⁻⁶ M (for example, 10 ⁻¹ M to 10 ⁻⁶ M, 10 ⁻¹ M to 10 ⁻⁵ M, 10 ^-2 M to 10 ^-4 M). In some embodiments, the non-target refers to an antigen other than MASP2. Thus, in some embodiments, the Kd value for binding between an anti-MASP2 antibody and a non-MASP2 target is 10 ⁻¹ M to 10 ⁻⁶ M, 1×10 ⁻¹ M to 5×10 ⁻⁶ M, 10 ⁻¹ M to 10 ^-5 M, 1×10 ^-1 M to 5×10 ^-5 M, 10 ^-1 M to 10 ^-4 M, 1×10 -1 M to 5× ^{10 -4} ^M , 10 ^-1 M to 10 ^-3 M, 1×10 ^-1 M to 5×10 ^-3 M, 10 ^-1 M to 10 ^-2 M, 10 ^-2 M to 10 ^-6 M, 1×10 ^-2 M to 5×10 ^-6 M, 10 ^-2 M to 10 ^-5 M, 1×10 ^-2 M to 5×10 ^-5 M, 10 ^-2 M to 10 ^-4 M, 1×10 ^-2 M to 5×10 ^-4 M, 10 ^- ² M to 10 ^-3 M, 10 ^-3 M to 10 ^-6 M, 1×10 ^-3 M to 5×10 ^-6 M, 10 ^-3 M to 10 ^-5 M, 1×10 ^-3 M to 5×10 ^-5 M, 10 ^-3 M to 10 ^-4 M, 10 ^-4 M to 10 ^-6 M, 1×10 -4 M to 5×10 ^-6 M, ^{10 -4} ^M to 10 ^-5 M, 10 ^-5 M to 10 ^-6 M.

In some embodiments, when referring to an anti-MASP2 antibody that specifically recognizes a MASP2 target with high binding affinity and binds a non-target with low binding affinity, the anti-MASP2 antibody binds to a MASP2 target with a Kd value of 10 ⁻⁷ M to 10 ^-13 M (eg 10 ^-7 M to 10 ^-13 M, 10 ^-8 M to 10 ^-13 M, 10 ^-9 M to 10 -13 M, 10 ^-10 ^M to 10 ^-12 M), and with The Kd value for non-target binding is 10 ⁻¹ M to 10 ⁻⁶ M (eg, 10 ⁻¹ M to 10 ⁻⁶ M, 10 ⁻¹ M to 10 ⁻⁵ M, 10 ⁻² M to 10 ⁻⁴ M).

In some embodiments, where the anti-MASP2 antibody specifically recognizes MASP2, the binding affinity of the anti-MASP2 antibody is compared to the binding affinity of a control anti-MASP2 antibody (eg, OMS721). In some embodiments, the Kd value of the binding between the control anti-MASP2 antibody and MASP2 may be at least 2 times, such as 2 times, 3 times, 4 times, the Kd value of the binding between the anti-MASP2 antibody described herein and MASP2 , 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 10-100 times, 100-1000 times, 10 ³ -10 ⁴ times.

nucleic acid

Nucleic acid molecules encoding anti-MASP2 antibodies are also contemplated. In some embodiments, a nucleic acid (or set) encoding a full-length anti-MASP2 antibody is provided, including any one of the full-length anti-MASP2 antibodies described herein. In some embodiments, the nucleic acid (or a set of nucleic acids) of the anti-MASP2 antibody described herein may also include a nucleic acid sequence encoding a polypeptide tag (eg, protein purification tag, His tag, HA tag).

Also contemplated herein is an isolated host cell comprising an anti-MASP2 antibody, an isolated nucleic acid encoding an anti-MASP2 antibody polypeptide component, or a vector comprising a nucleic acid encoding an anti-MASP2 antibody polypeptide component described herein.

The present application also includes variants of these nucleic acid sequences. For example, a variant includes a nucleotide sequence that hybridizes to a nucleic acid sequence encoding an anti-MASP2 antibody of the present application at least under moderately stringent hybridization conditions.

The present application also provides a vector into which the nucleic acid sequence of the present application can be inserted.

Briefly, a natural or synthetic nucleic acid encoding an anti-MASP2 antibody is inserted into a suitable expression vector such that the nucleic acid is operably linked to 5' and 3' regulatory elements, including, for example, promoters (e.g., lymphocyte-specific promoter) and 3' untranslated region (UTR), can express anti-MASP2 antibody (such as full-length anti-MASP2 antibody). The vectors are suitable for replication and integration in eukaryotic host cells. Typical cloning and expression vectors contain transcriptional and translational terminators, initiation sequences and promoters to regulate the expression of the nucleic acid sequence of interest.

The nucleic acids described herein can also be used in nucleic acid immunization and gene therapy by using standard gene delivery protocols. Methods of nucleic acid delivery are known in the art. See, eg, U.S. Pat. Nos. 5,399,346, 5,580,859, 5,589,466, the entire contents of which are incorporated herein by reference. In some embodiments, the present application also provides gene therapy vectors.

Nucleic acids can be cloned into many types of vectors. For example, nucleic acids can be cloned into vectors including, but not limited to, plasmids, phagemids, phage derivatives, animal viruses, and cosmids. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors and sequencing vectors.

In addition, expression vectors can be provided to cells in the form of viral vectors. Viral vector technology is well known in the art and described, for example, in Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York), among other virology or molecular biology manuals. Viruses that can be used as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses. Generally, suitable vectors include an origin of replication functional in at least one organism, a promoter sequence, convenient restriction enzyme sites, and one or more selectable markers (see, e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No. 6,326,193).

A number of virus-based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. The selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus is then isolated and delivered to cells of the subject either in vivo or in vitro. Many retroviral systems are known in the art. In some embodiments, adenoviral vectors are used. Many adenoviral vectors are known in the art. In some embodiments, lentiviral vectors are used. Vectors derived from retroviruses, such as lentiviruses, are suitable tools for long-term gene transfer because they allow long-term stable integration of the transgene and propagation in progeny cells. Lentiviral vectors have an additional advantage over tumor-derived retroviruses such as murine leukemia virus in that they can transduce non-dividing cells such as hepatocytes. At the same time, it has the added advantage of low immunogenicity.

Other promoter elements, such as enhancers, regulate transcription initiation frequency. Typically they are located 30-110 bp upstream of the initiation site, although it has recently been discovered that many promoters also contain functional elements downstream of the initiation site. The spacing between promoter elements is usually flexible so that promoter function is maintained when elements are swapped or moved relative to each other. In the thymidine kinase (tk) promoter, activity begins to decline when the spacing between promoter elements increases to 50 bp.

One example of a suitable promoter is the immediate early cytomegalovirus (CMV) promoter sequence. The promoter sequence is a strong constitutive promoter sequence, which can drive high-level expression of any polynucleotide sequence operably linked to it. Another example of a suitable promoter is the elongation factor 1 alpha (EF-1 alpha) promoter. However, other constitutive promoters can also be used, including but not limited to Simian virus 40 (SV40) early promoter, mouse mammary tumor virus (MMTV), human immunodeficiency virus long terminal repeat (HIV-LTR) promoter , MoMuLV promoter, avian leukemia virus promoter, Epstein-Barr virus immediate early promoter, Rous sarcoma virus promoter and human gene promoters, for example including but not limited to actin promoter, myosin promoter, Hemoglobin promoter and creatine kinase promoter. Furthermore, the application should not be limited to the use of only constitutive promoters, inducible promoters are also considered part of the application. The use of an inducible promoter provides a molecular switch that turns on expression of a polynucleotide sequence to which it is operably linked when such expression is desired and turns off expression when it is not. Inducible promoters include, but are not limited to, the metallothionein promoter, the glucocorticoid promoter, the progesterone promoter, and the tetracycline promoter.

In some embodiments, the expression of anti-MASP2 antibodies is inducible. In some embodiments, the nucleic acid sequence encoding the anti-MASP2 antibody is operably linked to an inducible promoter, including any of the inducible promoters described herein.

inducible promoter

The use of an inducible promoter provides a molecular switch that turns on expression of a polynucleotide sequence to which it is operably linked when expression is desired and turns off expression when expression is not desired. Exemplary inducible promoters suitable for use in eukaryotic cells include, but are not limited to, hormone regulatory elements (see, e.g., Mader, S. and White, J.H. (1993) Proc. Natl. Acad. Sci. USA 90:5603-5607) , synthetic ligand regulatory elements (seeing Spencer, D.M.et al (1993) Science 262:1019-1024) and ionizing radiation regulatory elements (seeing Manome, Y.et al. (1993) Biochemistry 32:10607-10613; Datta, R . et al. (1992) Proc. Natl. Acad. Sci. USA 89:1014-10153). See Gingrich et al. (1998) Annual Rev. Neurosci 21:377-405 for other exemplary inducible promoters suitable for use in mammalian systems in vivo or in vitro. In some embodiments, the inducible promoter system used to express the anti-MASP2 antibody is the Tet system. In some embodiments, the inducible promoter system used to express the anti-MASP2 antibody is the E. coli lac repression system.

An exemplary inducible promoter system employed herein is the Tet system. The system is based on the Tet system described by Gossen et al. (1993). In an exemplary embodiment, the polynucleotide of interest is controlled by a promoter comprising one or more Tet operator (TetO) sites. In the inactive state, the Tet repressor (TetR) binds to the TetO site and represses transcription from the promoter. In the activated state, e.g., in the presence of inducers such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox) or their active analogs, the inducer releases TetR from TetO, resulting in transcription . Doxycycline is a member of the tetracycline antibiotic family with the chemical name 1-dimethylamino-2,4a,5,7-pentahydroxy-11-methyl-4,6-dioxy-1,4a , 11,11a,12,12a-Hexahydrotetraene-3-carboxamide.

In one embodiment, TetR is codon optimized for expression in mammalian cells, such as mouse or human cells. Due to the degeneracy of the genetic code, most amino acids are encoded by more than one codon, resulting in a large number of variants in the sequence of a given nucleic acid without any change in the amino acid sequence it encodes. However, many organisms differ in their codon usage, also known as "codon bias" (ie, the preference for a given amino acid to use a particular codon). Codon bias is often associated with the presence of dominant tRNA species for specific codons, which in turn increases the efficiency of mRNA translation. A coding sequence derived from a particular species (e.g., prokaryotes) can thus be tailored by codon optimization to enhance its expression in a different species (e.g., eukaryotes).

Other specific variations of the Tet system include the "Tet-Off" and "Tet-On" systems below. In the Tet-off system, transcription is inactivated in the presence of Tc or Dox. In this system, a tetracycline-regulated transcriptional activator (tTA), consisting of TetR fused to the strong transcriptional activation domain of herpes simplex virus VP16, regulates the expression of target nucleic acids under the transcriptional control of a tetracycline-responsive promoter element (TRE). The TRE element consists of a TetO sequence fused in tandem to a promoter (usually a minimal promoter sequence derived from the human cytomegalovirus immediate early promoter). In the absence of Tc or Dox, tTA binds TRE and activates transcription of target genes. In the presence of Tc or Dox, tTA cannot bind TRE and target genes cannot be expressed.

In contrast, in the Tet-On system, transcription is activated in the presence of Tc or Dox. The Tet-On system is based on the reverse tetracycline-regulated transcriptional activator rtTA. Like tTA, rtTA is a fusion protein consisting of the TetR repressor and the VP16 transcriptional activation domain. However, a change of 4 amino acids in the DNA-binding region of TetR altered the binding properties of rtTA so that it could only recognize the tetO sequence on the target transgenic TRE in the presence of Dox. Therefore, in the Tet-On system, rtTA can activate the transcription of TRE-regulated target genes only in the presence of Dox.

Another inducible promoter system is the lac repressor system of E. coli (see Brown et al., Cell 49:603-612 (1987)). The Lac repressor system functions by regulating the transcription of a polynucleotide of interest operably linked to a promoter comprising the lac operator (lacO). The Lac repressor (lacR) binds to LacO, thereby preventing the transcription of the target polynucleotide. Expression of the polynucleotide of interest is induced by a suitable inducer, for example, isopropyl-β-Dthiogalactopyranoside (IPTG).

In order to assess the expression of the polypeptide or a portion thereof, the expression vector to be introduced into the cells may also contain a selectable marker gene or a reporter gene or both to facilitate the identification and selection of expressing cells from a population of cells transfected or infected with the viral vector. In other aspects, selectable markers can be carried on separate DNA fragments and used in co-transfection experiments. Either a selectable marker gene or a reporter gene can be flanked by appropriate regulatory sequences to enable its expression in the host cell. Useful selectable markers include, for example, antibiotic resistance genes such as neo and the like.

Reporter genes can be used to identify potentially transfected cells and evaluate the function of regulatory sequences. Typically, a reporter gene is a gene not present in or expressed by a recipient organism or tissue that encodes a polypeptide whose expression is manifested by some readily detectable property, such as enzymatic activity. After the DNA is introduced into the recipient cells, the expression of the reporter gene is detected at an appropriate time. Suitable reporter genes may include genes encoding luciferase, β-galactosidase, chloramphenicol acetyltransferase, secreted alkaline phosphatase, or green fluorescent protein (see, Ui-Tel et al., 2000 FEBS Letters 479: 79-82). Suitable expression systems are known and can be prepared by known techniques or obtained commercially. In general, the construct with the smallest 5' flanking region that exhibits the highest expression level of the reporter gene is considered a promoter. Such a promoter region can be linked to a reporter gene and used to assess the ability of certain substances to regulate transcription driven by the promoter.

In some embodiments, a nucleic acid encoding any of the full-length anti-MASP2 antibodies described herein is provided. In some embodiments, the nucleic acid includes one or more nucleic acid sequences encoding full-length anti-MASP2 antibody heavy and light chains. In some embodiments, each of the one or more nucleic acid sequences is contained in a separate vector. In some embodiments, at least some of the nucleic acid sequences are contained within the same vector. In some embodiments, all nucleic acid sequences are contained within the same vector. Vectors can be selected, for example, from mammalian expression vectors and viral vectors (such as vectors derived from retroviruses, adenoviruses, adeno-associated viruses, herpesviruses, and lentiviruses).

Methods for introducing and expressing genes into cells are known in the art. In the context of expression vectors, the vectors can be readily introduced into host cells, such as mammalian, bacterial, yeast or insect cells, by any method in the art. For example, expression vectors can be introduced into host cells by physical, chemical or biological methods.

Physical methods for introducing polynucleotides into host cells include calcium phosphate precipitation, lipofection, biolistics, microinjection, electroporation, and the like. Methods for preparing cells comprising vectors and/or exogenous nucleic acids are well known in the art. See, eg, Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). In some embodiments, polynucleotides are introduced into host cells by calcium phosphate transfection.

Biological methods for introducing polynucleotides of interest into host cells include the use of DNA and RNA vectors. Viral vectors, especially retroviral vectors, have become the most widely used method for inserting genes into mammalian cells, such as human cells. Other viral vectors can be derived from lentiviruses, poxviruses, herpes simplex virus type 1, adenoviruses, and adeno-associated viruses, among others. See, eg, U.S. Pat. Nos. 5,350,674 and 5,585,362.

Chemical methods for introducing polynucleotides into host cells include colloidal dispersion systems such as polymer complexes, nanocapsules, microspheres, magnetic beads and lipid-based systems including oil-in-water emulsions, micelles, mixed gels clumps and liposomes. An exemplary colloidal system used as a delivery vehicle in vivo and in vitro is a liposome (eg, an artificial membrane vesicle).

Where a non-viral delivery system is used, an exemplary delivery vehicle is a liposome. Consider using lipid formulations to introduce nucleic acids into host cells (in vitro, ex vivo, or in vivo). In another aspect, the nucleic acid can be bound to a lipid. Lipid-bound nucleic acids can be encapsulated into the aqueous interior of liposomes, dispersed within the lipid bilayer of liposomes, attached to liposomes via linker molecules that bind liposomes and oligonucleotides, and include Buried in liposomes, complexed with liposomes, dispersed in lipid-containing solutions, mixed with lipids, associated with lipids, suspended in lipids, contained in or mixed with micelles , or otherwise bind to lipids. Lipid, lipid/DNA or lipid/expression vector-related compositions are not limited to any particular structure in solution. For example, they may exist in bilayer structures, in micelles or in "collapsed" structures. They can also simply disperse in solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances, either naturally occurring or synthetic. For example, lipids include fat droplets naturally present in the cytoplasm, as well as a class of compounds containing long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, aminoalcohols, and aldehydes.

Regardless of the method used to introduce exogenous nucleic acid into the host cell or otherwise expose the cell to the inhibitors of the present application, a variety of experiments can be performed to confirm the presence of the recombinant DNA sequence in the host cell. Such experiments include, for example, "molecular biology" experiments well known to those skilled in the art. Examples include Southern and Northern blotting, RT-PCR, and PCR; "biochemical" assays, such as detection of the presence or absence of a specific polypeptide, e.g. identified by immunological methods (ELISAs and Western blots) or by assays described herein All fall within the scope of this application.

Preparation of anti-MASP2 antibody

In some embodiments, the anti-MASP2 antibody is or is derived from a monoclonal antibody. In some embodiments, the anti-MASP2 antibody comprises _VH and _VL from a monoclonal antibody, or a variant thereof. In some embodiments, the anti-MASP2 antibody further comprises CH1 and CL regions from a monoclonal antibody, or a variant thereof. Monoclonal antibodies can be prepared using, for example, methods known in the art, including hybridoma cell methods, phage display methods, or using recombinant DNA methods. Additionally, exemplary phage display methods are described herein and in the Examples below.

In the hybridoma cell method, hamsters, mice or other suitable host animals are usually immunized with an immunizing agent to induce lymphocytes that produce or are capable of producing antibodies that specifically bind to the immunizing agent. Alternatively, lymphocytes can be immunized in vitro. Immunizing agents may include polypeptides or fusion proteins of the protein of interest. Typically, peripheral blood lymphocytes (PBLs) are used if cells of human origin are desired, whereas splenocytes or lymph node cells are used if cells of non-human mammalian origin are desired. Lymphocytes are fused with an immortal cell line using an appropriate fusion agent, such as polyethylene glycol, to form hybridoma cells. Immortal cell lines are usually transformed mammalian cells, especially myeloma cells of rodent, bovine and human origin. Typically rat or mouse myeloma cell lines are used. Hybridoma cells can be cultured in a suitable medium, which preferably contains one or more substances that inhibit the growth or survival of unfused immortalized cells. For example, if the parental cells lack hypoxanthine-guanine phosphoribosyltransferase (HGPRT or HPRT), the hybridoma cell culture medium usually includes hypoxanthine, aminopterin, and thymidine (HAT medium), which can Prevents the growth of HGPRT-deficient cells.

In some embodiments, the immortalized cell line fuses efficiently, ensures high level and stable expression of antibody by the selected antibody-producing cells, and is sensitive to certain medium, such as HAT medium. In some embodiments, the immortal cell line is a mouse myeloma cell line available from, eg, the Salk Cell Collection, San Diego, California, and the American Type Culture Collection, Manassas, Virginia. Human myeloma and mouse-human hybrid myeloma cell lines are also described for the production of human monoclonal antibodies.

The medium in which the hybridoma cells are grown can then be assayed for the presence of monoclonal antibodies directed against the polypeptide. The binding specificity of monoclonal antibodies produced by hybridoma cells can be determined by immunoprecipitation or in vitro binding assays, such as radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA). Such techniques or analytical methods are known in the art. The binding affinity of monoclonal antibodies can be determined by Scatchard analysis as described, for example, in Munson and Pollard, Anal. Biochem., 107:220 (1980).

After the desired hybridoma cells have been identified, the clones of interest can be subcloned by limiting dilution and cultured by standard methods. Suitable media for this purpose include, for example, Modified Eagle's Medium (DMEM) and RPMI-1640 medium. Alternatively, hybridoma cells can be grown in ascites in mammals.

Monoclonal antibodies secreted by subclones can be isolated or purified from culture medium or ascitic fluid by conventional immunoglobulin purification methods, such as protein A-Sepharose, hydroxyapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.

In some embodiments, according to any anti-MASP2 antibody described herein, the anti-MASP2 antibody comprises a sequence selected from a clone of an antibody library (eg, a phage library displaying scFv or Fab fragments). Such clones can be identified by screening a combinatorial library of antibody fragments having the desired activity. For example, various methods are known in the art for generating phage display libraries and screening these libraries for antibodies with desired binding properties. These methods are reviewed in, for example, Hoogenboom et al., Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press, Totowa, N.J., 2001), and in, for example, McCafferty et al. , Nature 348:552-554; Clackson et al., Nature 352:624-628 (1991); Marks et al., J.Mol.Biol.222:581-597 (1992); Marks and Bradbury, Methods in Molecular Biology 248:161-175 (Lo, ed., Human Press, Totowa, N.J., 2003); Sidhu et al., J. Mol. Biol. 338(2):299-310 (2004); Lee et al., J.Mol.Biol.340(5):1073-1093(2004); Fellouse, Proc.Natl.Acad.Sci.USA 101(34):12467-12472(2004); and Lee et al., J.Immunol Further described in Methods 284(1-2):119-132 (2004).

In some phage display methods, the repertoires of the _VH and _VL genes are cloned separately by polymerase chain reaction (PCR), randomly recombined in a phage library, and then screened for antigen-binding phage, as in Winter et al. ., Ann. Rev. Immunol., 12:433-455 (1994). Phage typically display antibody fragments as scFv fragments or as Fab fragments. Immune-derived library phages provide high-affinity antibodies against the immunogen without the need to construct hybridoma cells. Alternatively, natural repertoires (e.g. from humans) can be cloned to provide a single source of antibodies against multiple non-self and self-antigens without any immunization, as in Griffiths et al., EMBO J, 12:725-734 (1993 ) described in . Finally, natural libraries can also be prepared by cloning non-rearranged V-gene fragments from stem cells, using PCR primers containing random sequences encoding CDR3 hypervariable regions, and completing rearrangement in vitro, such as Hoogenboom and Winter, J. Described in Mol. Biol., 227:381-388 (1992). Patent publications describing human antibody phage libraries include, for example, US Pat. No. 5,750,373 and US Patent Publication Nos. 7/0292936 and 2009/0002360.

The anti-MASP2 antibody is prepared by phage display screening the anti-MASP2 antibody part in the library that can specifically bind to the target MASP2. The library can be a human scFv phage display library with at least 1×10 ⁹ (e.g. at least 1×10 ⁹ , 2.5×10 ⁹ , 5×10 ⁹ , 7.5×10 ⁹ , 1×10 ¹⁰ , 2.5×10 ¹⁰ , 5 ×10 ¹⁰ , 7.5×10 ¹⁰ , or 1×10 ¹¹ ) diversity of unique human antibody fragments. In some embodiments, the library is a natural human library constructed from DNA extracted from PMBCs and spleens of healthy subjects, comprising all human heavy and light chain subfamilies. In some embodiments, the library is a human natural library constructed by DNA extracted from PMBCs isolated from patients with various diseases, such as patients with autoimmune diseases, cancer patients and patients with infectious diseases. In some embodiments, the library is a semi-synthetic human library in which the heavy chain CDR3s are completely randomized, with all amino acids (except cysteine) present at any given position with equal probability. (See eg, Hoet, RM et al., Nat. Biotechnol. 23(3):344-348, 2005). In some embodiments, the semi-synthetic human library has a heavy chain CDR3 length of 5 to 24 (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 , 19, 20, 21, 22, 23 or 24) amino acids. In some embodiments, the library is a fully synthetic phage display library. In some embodiments, the library is a non-human phage display library.

Phage clones with high affinity to target MASP2 can be screened by iterative binding of phage to target MASP2 bound to a solid support (e.g. beads for solution panning or mammalian cells for cell panning). ), followed by removal of unbound phage and elution of specifically bound phage. Subsequently, bound phage clones are eluted and used to infect suitable host cells, such as E.coli XL1-Blue, for expression and purification. Multiple rounds of panning (eg, 2, 3, 4, 5, 6 or more rounds), such as solution panning, cell panning, or a combination of both can be performed to enrich for phage clones that specifically bind to MASP2. Specific binding of the enriched phage clones to the target MASP2 can be detected by any method known in the art, including, for example, ELISA and FACS.

Another way to screen antibody libraries is to display proteins on the surface of yeast cells. Wittrup et al. (US Patents 6,699,658 and 6,696,251) developed a method for displaying libraries in yeast cells. In this yeast display system, one component includes the yeast lectin protein (Aga1) anchored on the yeast cell wall, and the other component includes the second subunit of the lectin protein Aga2, which can Combined with Aga1 protein and displayed on the surface of yeast cells. The Agal protein is expressed by integrating the Agal gene into the yeast chromosome. After transformation of a single-chain variable fragment (scFv) library fused to the Aga2 gene in a yeast display plasmid, the library is retained in yeast due to the presence of an additional nutritional marker. Both Aga1 and Aga2 proteins are expressed under the control of a galactose-inducible promoter.

Human antibody V gene repertoires ( _VH and _VK fragments) were obtained by the PCR method using a set of degenerate primers (Sblattero, D. and Bradbury, A. Immunotechnology 3, 271-278 1998). PCR templates were derived from commercially available RNA or cDNA, including PBMC, spleen, lymph node, bone marrow and tonsil. After combining independent _VH and _VK PCR libraries, they were assembled into scFv format by overlap extension PCR (Sheets, MD et al, Proc. Natl. Acad. Sci. USA 95, 6157-6162 1998). To construct a yeast scFv display library, the resulting scFv PCR product was cloned into a yeast display plasmid in yeast by homologous recombination. (Chao, G, et al, Nat Protoc. 2006; 1(2):755-68. Miller KD, et al. Current Protocols in Cytometry 4.7.1-4.7.30, 2008).

Anti-MASP2 antibodies can be screened using a mammalian cell display system, wherein antibody portions are displayed on the surface of cells and antibodies specifically targeting MASP2 are isolated by antigen-directed screening methods (as described in U.S. Patent No. 7,732,195 B2). A library of Chinese hamster ovary (CHO) cells displaying a large number of human IgG antibody genes can be created and used to discover clones expressing high-affinity antibody genes. An alternative display system has been developed that enables simultaneous cell surface display and secretion of the same protein through alternative splicing, where the displayed protein phenotype remains genotype-related, enabling simultaneous biophysical and cellular function-based analysis The secreted soluble antibody was characterized in . This method overcomes many of the limitations of previous mammalian cell displays and enables direct screening and maturation of antibodies in the form of full-length, glycosylated IgGs (Peter M. Bowers, et al, Methods 2014, 65: 44-56) . Transient expression systems are suitable for single rounds of antigen selection prior to antibody gene restoration and are therefore most useful for selecting antibodies from smaller libraries. Stable exosome vectors offer an attractive option. Exosome vectors can be efficiently transfected and stably maintained at low copy numbers, allowing multiple rounds of panning and resolution of more complex antibody repertoires.

The IgG library is constructed based on the ligation of germline sequence V gene segments isolated from a panel of human donors with rearranged (D)J regions. RNA collected from 2000 human blood samples was reverse transcribed into cDNA, V _H and V _K fragments were amplified using V _H and V _K specific primers, and purified by gel extraction. IgG libraries were prepared by subcloning _VH and _VK fragments into display vectors containing IgG1 or K constant regions, respectively, and then electroporating or transducing 293T into cells. To prepare scFv antibody display libraries, _VH and _VK were ligated to generate scFv, which was then subcloned into a display vector, which was then electroporated or transduced into 293T cells. As we all know, IgG libraries are constructed based on germline sequence V gene fragments and rearranged (D)J regions isolated from a group of donors, which can be mice, rats, rabbits or monkeys.

Monoclonal antibodies can also be prepared by recombinant DNA methods, such as described in U.S. Patent No. 4,816,567. DNA encoding the monoclonal antibodies described in this application can be easily isolated and sequenced by conventional methods (eg, by oligonucleotide probes that can specifically bind to genes encoding the light and heavy chains of murine antibodies). Hybridoma cells as described above or MASP2-specific phage clones of the present application can be used as a source of such DNA. After isolation, the DNA can be placed in an expression vector, which is then transfected into host cells, such as simian COS cells, Chinese hamster ovarian cancer (CHO) cells, or non-immunoglobulin-producing myeloma cells, to obtain Monoclonal antibodies synthesized in cells. The DNA can also be modified, for example by replacing human heavy and light chain constant regions with coding sequences and/or by replacing homologous non-human sequences with framework regions (U.S. Patent No. 4,816,567; Morrison et al., supra), or by A coding sequence of a non-immunoglobulin polypeptide covalently linked to all or part of a coding sequence of an immunoglobulin. This non-immunoglobulin polypeptide can replace the constant region of the antibody of the present application, or can replace an antigen-binding site in the variable domain of the antibody of the present application to form a chimeric bivalent antibody.

The antibody can be a monovalent antibody. Methods of making monovalent antibodies are known in the art. For example, one method involves recombinant expression of an immunoglobulin light chain and a modified heavy chain. Heavy chains are typically truncated anywhere in the Fc region to prevent cross-linking of the heavy chains to each other. Alternatively, the relevant cysteine residues are substituted with other amino acid residues or deleted to prevent cross-linking.

In vitro methods are also suitable for preparing monovalent antibodies. Digestion of antibodies to produce antibody fragments, particularly Fab fragments, can be accomplished using any method known in the art.

Antibody variable domains with the desired binding specificity (antibody-antigen combining site) can be fused to immunoglobulin constant regions. The fusion is preferably to an immunoglobulin heavy chain constant region, which includes at least part of the hinge, CH2 and CH3 regions. In some embodiments, the first heavy chain constant region (CH1) comprising the site necessary for light chain binding is present in at least one fusion. DNA encoding the fusion of the immunoglobulin heavy chain and, if desired, the DNA encoding the light chain of the immunoglobulin is inserted into a separate expression vector and co-transfected into a suitable host organism.

Fully Human and Humanized Antibodies

The anti-MASP2 antibody (such as a full-length anti-MASP2 antibody) can be a fully human antibody or a humanized antibody. Humanized forms of non-human (e.g., mouse) antibody portions are chimeric immunoglobulins, immunoglobulin chains, or fragments thereof (e.g., Fv, Fab, Fab', F(ab') ₂ , scFv, or other fragments of antibodies). Antigen-binding subsequences), which generally include minimal sequence derived from non-human immunoglobulins. Humanized antibodies include human immunoglobulins, immunoglobulin chains or fragments thereof (recipient antibodies) in which residues from the recipient CDRs are replaced by non-human (donor antibody) CDRs having the desired specificity, affinity and properties. Substitution of residues, such as mouse, rat or rabbit CDRs. In some embodiments, human immunoglobulin Fv framework region residues are substituted by corresponding non-human residues. Humanized antibodies may also comprise amino acid residues that are found neither in the recipient antibody nor in imported CDR or framework region sequences. Generally, humanized antibodies will comprise at least one, and usually two, variable domains in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and in which all or substantially all of the framework regions are common to human immunoglobulins. sequence.

Typically, humanized antibodies contain one or more amino acid residues that have been introduced from a non-human source. Those non-human amino acid residues are often referred to as "imported" residues, usually from an "imported" variable domain. According to some embodiments, humanization can basically be carried out according to the following method of Winter and its colleagues (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 ( 1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of human antibodies. Thus, such "humanized" antibody portions (U.S. Patent No. 4,816,567), which are substantially less than fully human antibodies, have variable domains replaced by corresponding sequences from non-human sources. In practice, a humanized antibody portion is that portion of a typically human antibody in which some CDR residues and possibly some framework region residues are substituted by residues from analogous sites in rodent antibodies.

Fully human antibodies are an alternative to humanization. For example, transgenic animals (eg, mice) that are capable of producing a fully human antibody library upon immunization but not endogenous immunoglobulins are currently produced. For example, it has been reported that homozygous deletion of the antibody heavy-chain joining region (JH) gene in chimeric and germline mutant mice completely suppresses endogenous antibody production. Transfer of human germline immunoglobulin gene arrays into such germline mutant mice produces human antibodies upon antigen stimulation, see, e.g., akobovits et al., PNAS USA, 90:2551 (1993); Jakobovits et al ., Nature, 362:255-258 (1993); Bruggemann et al., Year in Immunol., 7:33 (1993); U.S. Patent Nos. 5,545,806, 5,569,825, 5,591,669, 5,545,807; and WO 97/17852. Alternatively, fully human antibodies can be prepared by introducing human immunoglobulin loci into transgenic animals (eg, mice in which endogenous immunoglobulin genes have been partially or fully silenced). After antigen stimulation, it can be found that the production of fully human antibodies is very similar to that in humans in all aspects, including gene rearrangement, assembly and antibody library. This method is described, for example, in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 368: 856-859 (1994); Morrison, Nature, 368:812-813 (1994); Fishwild et al., Nature Biotechnology, 14:845-851 (1996); Neuberger, Nature Biotechnology, 14:826 (1996); Lonberg and Huszar, Intern. Rev. Immunol., 13:65-93 (1995).

Fully human antibodies can also be produced by in vitro activation of B cells (see U.S. Patents 5,567,610 and 5,229,275) or by using various techniques known in the art, including phage display libraries. Hoogenboom and Winter, J.Mol.Biol., 227:381 (1991); Marks et al., J.Mol.Biol., 222:581 (1991). Techniques of Cole et al. and Boerner et al. It can also be used to prepare fully human monoclonal antibodies. See Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985) and Boerner et al., J. Immunol., 147(1):86-95 (1991).

Anti-MASP2 Antibody Variants

In some embodiments, the amino acid sequences of anti-MASP2 antibody variants provided herein (eg, full-length anti-MASP2 antibodies) are also contemplated. For example, it may be desirable to improve the binding affinity and/or other biological activity of the antibody. The amino acid sequences of antibody variants can be prepared by introducing appropriate modifications into the antibody-encoding nucleotide sequence or by peptide synthesis. Such modifications include, for example, deletions and/or insertions and/or substitutions of residues in the antibody amino acid sequence. The final construction can be accomplished by any combination of amino acid residue deletions, insertions, and substitutions to impart the desired characteristics. For example, antigen binding.

In some embodiments, anti-MASP2 antibody variants having one or more amino acid substitutions are provided. Target sites for substitution mutations include hypervariable regions (HVRs) and framework regions (FRs). Amino acid substitutions can be introduced in the antibody of interest and the product screened for desired activity, for example, improved biological activity, retained/improved antigen binding ability, reduced immunogenicity, or improved ADCC or CDC.

Conservative substitutions are shown in Table 4 below.

Table 4 Conservative substitutions

原始残基original residue	示例性取代exemplary substitution	优选取代preferred substitution
Ala(A)Ala(A)	Val；Leu；IleVal; Leu; Ile	ValVal
Arg(R)Arg(R)	Lys；Gln；AsnLys; Gln; Asn	LysLys
Asn(N)Asn(N)	Gln；His；Asp,Lys；ArgGln; His; Asp, Lys; Arg	GlnGln
Asp(D)Asp(D)	Glu；AsnGlu;Asn	GluGlu
Cys(C)Cys(C)	Ser；AlaSer; Ala	SerSer
Gln(Q)Gln(Q)	Asn；GluAsn; Glu	AsnAsn
Glu(E)Glu(E)	Asp；GlnAsp; Gln	AspAsp
Gly(G)Gly(G)	AlaAla	AlaAla
His(H)His(H)	Asn；Gln；Lys；ArgAsn; Gln; Lys; Arg	ArgArg
Ile(I)Ile (I)	Leu；Val；Met；Ala；Phe；NorleucineLeu; Val; Met; Ala; Phe; Norleucine	LeuLeu
Leu(L)Leu(L)	Norleucine；Ile；Val；Met；Ala；PheNorleucine; Ile; Val; Met;	IleIle
Lys(K)Lys(K)	Arg；Gln；AsnArg; Gln; Asn	ArgArg
Met(M)Met(M)	Leu；Phe；IleLeu; Phe; Ile	LeuLeu
Phe(F)Phe(F)	Trp；Leu；Val；Ile；Ala；TyrTrp; Leu; Val; Ile; Ala; Tyr	TyrTyr
Pro(P)Pro(P)	AlaAla	AlaAla
Ser(S)Ser(S)	ThrThr	ThrThr
Thr(T)Thr(T)	Val；SerVal;	SerSer
Trp(W)Trp(W)	Tyr；PheTyr; Phe	TyrTyr
Tyr(Y)Tyr(Y)	Trp；Phe；Thr；SerTrp; Phe; Thr; Ser	PhePhe
Val(V)Val(V)	Ile；Leu；Met；Phe；Ala；NorleucineIle; Leu; Met; Phe; Ala; Norleucine	LeuLeu

Amino acids are divided into different classes according to their side chain properties:

a. Hydrophobic amino acids: norleucine Norleucine, methionine Met, alanine Ala, valine Val, leucine Leu, isoleucine Ile;

b. Neutral hydrophilic amino acids: cysteine Cys, serine Ser, threonine Thr, asparagine Asn, glutamine Gln;

c. Acidic amino acids: aspartic acid Asp, glutamic acid Glu;

d. Basic amino acids: histidine His, lysine Lys, arginine Arg;

e. Contain amino acids that affect the chain direction: glycine Gly, proline Pro;

f. Aromatic amino acids: tryptophan Trp, tyrosine Tyr, phenylalanine Phe.

Substitution of non-conservative amino acids involves substitution of one of the above classes for another class.

An exemplary substitution variant is an affinity matured antibody, which can be conveniently generated using, for example, phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated, the variant antibodies are partially displayed on phage, and screened for specific biological activities (e.g., activity to inhibit deposition of complement factors C4b, C3b, or MAC or increased antibody affinity) Variants. Alterations (eg, substitutions) in regions of the HVRs can be made to achieve improved activity or antibody affinity for complement factor C4b, C3b or MAC deposition. Alterations can be made in HVR "hotspot regions", i.e. residues encoded by codons that are highly mutated during somatic cell maturation (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008)), And/or at specific determinant residues (SDRs), the resulting variants _VH and _VL are tested for binding affinity. Methods for the construction and reselection of affinity maturation from secondary libraries have been described, for example, Hoogenboom et al. in Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press , Totowa, NJ, (2001)).

In some affinity maturation embodiments, diversity is introduced into the variable genes selected for affinity maturation by any of a variety of methods (e.g., error-prone PCR, strand shuffling, or oligonucleotide-directed mutagenesis) . Secondary libraries are then created. This library is screened to identify antibody variants with the desired affinity. Another method of introducing diversity involves an HVR-mediated approach, in which several HVR residues (eg, 4-6 residues at a time) are randomized. HVR residues involved in antigen binding are specifically identified, for example, using alanine scanning mutagenesis or modeling. Often the CDR-H3 and CDR-L3 regions in particular are key targets.

In some embodiments, substitutions, insertions, or deletions may occur within one or more of the HVRs, so long as such alterations do not substantially reduce the ability of the antibody to bind antigen. For example, conservative changes (eg, conservative substitutions provided herein) can be made in HVRs that do not substantially reduce binding affinity. These changes may occur outside of HVR "hot spots" or SDRs. In some embodiments of the variant _VH and _VL sequences provided above, each HVR is either unchanged or comprises no more than 1, 2 or 3 amino acid substitutions.

A useful method for identifying amino acid residues or regions of an antibody that can be targeted for mutation is called "alanine scanning mutagenesis" as described in Cunningham and Wells (1989) Science, 244:1081-1085 . In this method, one or a group of target residues (e.g., charged residues such as arginine, aspartic acid, histidine, lysine, and glutamic acid) are replaced by neutral or negatively charged amino acids (e.g., , alanine or glutamic acid) to determine whether the interaction between the antibody and the antigen is affected. Further substitutions can be introduced at the amino acid position to demonstrate that the position is functionally sensitive to the initial substitution. Alternatively, or additionally, the contact sites between the antibody and the antigen are identified by the crystal structure of the antigen-antibody complex. These contact residues and neighboring residues can be targeted or eliminated as candidates for substitution. Variants are screened to determine whether they possess the desired properties.

Amino acid sequence insertions, including amino-terminal and/or carboxy-terminal fusions, ranging in length from 1 residue to polypeptides containing 100 or more residues, also include intrasequence insertions of 1 or more amino acid residues base. Examples of terminal insertions include antibodies with a methionyl residue at the N-terminus. Other insertional variants of antibody molecules include fusions to the N-terminus or C-terminus of the antibody molecule of an enzyme (eg, ADEPT) or a polypeptide that increases the serum half-life of the antibody.

Fc region variants

In some embodiments, one or more amino acid modifications are introduced into the Fc region of an antibody described herein (eg, a full-length anti-MASP2 antibody or an anti-MASP2 antibody fusion protein), resulting in an Fc region variant. In some embodiments, Fc region variants have enhanced ADCC potency, typically associated with Fc-binding receptors (FcRs). In some embodiments, the Fc region variant has reduced ADCC potency. There are many examples of changes or mutations in the Fc sequence affecting its potency, for example, WO 00/42072 and Shields et al. J Biol. Chem. 9(2):6591-6604 (2001) describe enhanced binding to FcRs or Weakened antibody variants. The contents of these publications are incorporated herein by reference.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is the mechanism of action of therapeutic antibodies against tumor cells. ADCC is a cell-mediated immune defense. When the antigen on the surface of the target cell membrane is bound by a specific antibody (eg, anti-MASP2 antibody), the effector cells of the immune system actively lyse the target cell (eg, cancer cell). Usually the ADCC effect involves NK cells activated by antibodies. NK cells express the Fc receptor CD16. This receptor recognizes and binds the Fc portion of an antibody molecule bound to the surface of a target cell. The most common Fc receptors on the surface of NK cells are CD16 or FcγRIII. Binding of Fc receptors to the Fc region of an antibody results in activation of NK cells, release of cytolytic granules, and subsequent apoptosis of target cells. The killing effect of ADCC on tumor cells can be determined by the specific experiment of NK-92 cells transfected with high-affinity FcR. The results were compared with wild-type NK-92 not expressing FcR.

In some embodiments, the present application also provides anti-MASP2 antibody variants (eg, full-length anti-MASP2 antibody variants) comprising an Fc region with some but not all effector functions, such that they have an extended half-life in vivo, however specific For effector functions (such as CDC or ADCC) that are dispensable or deleterious, such anti-MASP2 antibodies are ideal candidates for this application. The reduction/elimination of CDC and/or ADCC activity is confirmed by in vitro and/or in vivo cytotoxicity assays. For example, an Fc receptor (FcR) binding assay is used to confirm that the antibody lacks FcγR binding (and thus likely lacks ADCC activity) but retains FcRn binding. Among the main cells that mediate ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. FcR expression on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet Annu. Rev. Immunol. 9:457-492 (1991). Non-limiting examples of in vitro assessment of ADCC activity of target molecules are described in US Pat. ) and Hellstrom, I et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); US Pat. No. 5,821,337 (see Bruggemann, M. et al., J. Exp. Med. 166 : 1351-1361 (1987)). Alternatively, nonradioactive detection methods can be used (see, for example, ACTI ^™ Flow Cytometry Nonradioactive Cytotoxicity Assay (Cell Technology, Inc. Mountain View, Calif.) and CYTOTOX 96 ^™ Nonradioactive Cellular Toxicity assays (Promega, Madison, Wis.). Effector cells used in such assays include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK). Alternatively, ADCC activity of the molecule of interest is performed in vivo Assay, e.g., in an animal model, as described in Clynes et al.Proc.Nat'l Acad.Sci.USA 95:652-656 (1998). A C1q binding assay can also be performed to confirm that the antibody cannot bind to C1q , thus lacking CDC activity. See, for example, C1q and C3c binding ELISA in WO 2006/029879 and WO 2005/100402. To assess complement activation, a CDC assay can be performed (see, for example, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, MS et al., Blood 101:1045-1052 (2003); and Cragg, MS and MJGlennie, Blood 103:2738-2743 (2004)).Use methods known in the art to determine FcRn binding and clearance/half-life in vivo (see, eg, Petkova, SB et al., Int'l. Immunol. 18(12):1759-1769 (2006)).

Antibodies with reduced effector function include substitutions of one or more residues at residues 238, 265, 269, 270, 297, 327, and 329 of the Fc region (U.S. Pat. No. 6,737,056). These Fc variants include Fc variants with substitutions of two or more residues at positions 265, 269, 270, 297, and 327, including Fc variants known as "DANA", which have residues at positions 265 and 297 The base is substituted with alanine (U.S. Pat. No. 7,332,581).

Such antibody variants with increased or decreased binding to FcRs have been described (see, e.g., U.S. Pat. No. 6,737,056; WO2004/056312, and Shields et al., J. Biol. Chem. 9(2):6591-6604 (2001)).

In some embodiments, a variant of an anti-MASP2 antibody (eg, a full-length anti-MASP2 antibody) comprising a variant Fc region with one or more amino acid substitutions capable of enhancing ADCC effect is provided. In some embodiments, the Fc region variant comprises one or more amino substitutions capable of enhancing the ADCC effect, and these substitutions are at positions 298, 333 and/or 334 (EU residue numbering) of the Fc region. In some embodiments, the anti-MASP2 antibody (eg, full-length anti-MASP2 antibody) variant comprises amino acid substitutions at positions S298A, E333A, and K334A in the Fc region.

In some embodiments, alterations in the Fc region result in alterations (i.e., enhancement or attenuation) of Clq binding and/or complement-dependent cytotoxicity (CDC), see U.S. Pat. No. 6,194,551, WO 99/51642, and Idusogie et al. al., J. Immunol. 164:4178-4184 (2000).

In some embodiments, there is provided a variant of an anti-MASP2 antibody (eg, a full-length anti-MASP2 antibody) comprising a variant of the Fc region with one or more amino acid substitutions capable of extending half-life or enhancing interaction with an Fc receptor (FcRn ) combination. Antibodies with extended half-life and improved FcRn binding are described in US 2005/0014934A1 (Hinton et al.). These antibody Fc regions contain one or more amino acid substitutions that enhance the binding of the Fc region to FcRn. These Fc variants comprise 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 or One or more substitutions in residue 434, eg, substitution of residue 434 in the Fc region (U.S. Pat. No. 7,371,826).

See also Duncan & Winter, Nature 322:738-40 (1988); U.S. Pat. No. 5,648,260; U.S. Pat. No. 5,624,821 and WO 94/29351 for other examples of Fc region variants.

The present application contemplates anti-MASP2 antibodies (eg, full-length anti-MASP2 antibodies) comprising any one or combination of the Fc variants described herein.

Glycosylation variant

In some embodiments, an anti-MASP2 antibody provided herein (eg, a full-length anti-MASP2 antibody) is altered to increase or decrease the degree of glycosylation of the anti-NGF antibody. Addition or deletion of glycosylation sites on an anti-MASP2 antibody can be conveniently accomplished by altering the amino acid sequence of the anti-NGF antibody or a polypeptide portion thereof to add or remove one or more glycosylation sites.

Where the anti-MASP2 antibody contains an Fc region, the sugar attached to it can be altered. Native antibodies produced by mammalian cells typically comprise branched biantennary oligosaccharides, usually N-linked to the Fc region CH2 domain Asn297, see e.g. Wright et al., TIBTECH 15:26-32 (1997) . The oligosaccharides may comprise a variety of sugars such as mannose, N-acetylglucosamine (GlcNAc), galactose and sialic acid, as well as trehalose linked to the GlcNAc in the "stem" of the biantennary oligosaccharide structure. In some embodiments, oligosaccharide modifications can be made to the anti-MASP2 antibodies of the present application to generate anti-MASP2 antibody variants with certain improved properties.

The N-glycans linked to the CH2 domain of the Fc region are heterogeneous. Antibodies or Fc fusion proteins produced in CHO cells are fucosylated by fucosyltransferase activity, see Shoji-Hosaka et al., J. Biochem. 2006, 140:777-83. Typically, a small fraction of naturally occurring non-fucosylated IgGs can be detected in human serum. N-glycosylation of the Fc region is important for its binding to FcγRs; non-fucosylated N-glycans enhance the binding ability of Fc to FcγRIIIa. Enhanced binding to FcRIIIa results in enhanced ADCC effect, which is advantageous in certain antibody therapeutic applications where cytotoxicity is required.

In some embodiments, enhanced effector functions may be detrimental when Fc-mediated cytotoxicity is not desired. In some embodiments, the Fc fragment or CH2 domain is aglycosylated. In some embodiments, glycosylation is prevented by mutating the N-glycosylation site in the CH2 domain.

In some embodiments, anti-MASP2 antibody (e.g., full-length anti-MASP2 antibody) variants are provided that comprise an Fc region, wherein the carbohydrate structure attached to the Fc region has reduced fucose or lacks fucose, which may ADCC function will be enhanced. Specifically, provided herein are anti-MASP2 antibodies that have reduced fucose relative to the same anti-MASP2 antibodies produced by wild-type CHO cells. That is, they are characterized by having a lower amount of fucose than antibodies produced by native CHO cells (eg, CHO cells producing native glycosylated forms, CHO cells containing the native FUT8 gene). In some embodiments, the N-linked glycans of the anti-MASP2 antibody have less than 50%, 40%, 30%, 20%, 10%, or 5% fucose. For example, the fucose content of the anti-MASP2 antibody may be 1%-80%, 1%-65%, 5%-65%, or 20%-40%. In some embodiments, the N-linked glycans of the anti-MASP2 antibody do not comprise fucose, ie, wherein the anti-MASP2 antibody is completely fucose-free, or fucose-free, or afucosylated. The content of fucose was calculated by calculating the average content of fucose in the sugar chain attached to Asn297 relative to the total of all sugar structures (such as complex, hybrid or mannose structures) attached to Asn297 measured by MALDI-TOF mass spectrometry. Quantities are determined as described in WO 2008/077546. Asn297 refers to the asparagine residue located at position 297 of the Fc region (EU Fc region residue numbering system). However, Asn297 can also be located ±3 amino acids upstream or downstream of position 297, ie between positions 294 and 300, due to minor sequence variations of the antibody. These fucosylated variants may have enhanced ADCC function. See, eg, US Patent Publication Nos. US 2003/0157108 (Presta, L.), US 2004/0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to "afucosylated" or "fucose-deficient" antibody variants include, US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002 /0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; 586; WO 2005/035778; WO 2005 /053742; WO 2002/031140; Okazaki et al. J. Mol. Biol. 336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004). Cell lines capable of producing afucosylated antibodies include Lec13CHO cells lacking protein fucosylation function (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003 /0157108A1, Presta, L; and WO 2004/056312A1, Adams et al., especially Example 11), and gene knockout cell lines, such as α-1,6-fucosyltransferase gene, FUT8 gene knockout Removed CHO cells (see Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94 (4): 680-688 (2006); and WO2003 /085107).

Anti-MASP2 antibody (eg, full-length anti-MASP2 antibody) variants further provide bisected oligosaccharides, eg, wherein the biantennary oligosaccharide attached to the Fc region of the anti-MASP2 antibody is bisected by GlcNAc. Such anti-MASP2 antibody (eg, full-length anti-MASP2 antibody) variants may have reduced fucosylation and/or enhanced ADCC function. Examples of such antibody variants are in WO 2003/011878 (Jean-Mairet et al.); U.S. Pat. No. 6,602,684 (Umana et al.); US 2005/0123546 (Umana et al.), and Ferrara et al. , Biotechnology and Bioengineering, 93(5):851-861 (2006) described. Also provided are anti-MASP2 antibody (eg, full-length anti-MASP2 antibody) variants that have at least one galactose residue in the oligosaccharide linked to the Fc region. Such anti-MASP2 antibody variants may have enhanced CDC function. Such variants are described, for example, in WO 1997/30087 (Patel et al.); WO 1998/58964 (Raju, S.); and WO 1999/22764 (Raju, S.).

In some embodiments, the anti-MASP2 antibody (eg, full-length anti-MASP2 antibody) variant comprises an Fc region that binds FcyRIII. In some embodiments, the anti-MASP2 antibody (e.g., full-length anti-MASP2 antibody) variant comprising an Fc region has ADCC activity in the presence of human effector cells (e.g., T cells), or in combination with other antibodies having a human wild-type IgG1 Fc region. Enhanced ADCC activity in the presence of human effector cells compared to the same anti-MASP2 antibody (eg, full-length anti-MASP2 antibody).

cysteine engineered variants

In some embodiments, it is desirable to produce cysteine engineered anti-MASP2 antibodies (eg, full-length anti-MASP2 antibodies) in which one or more amino acid residues are substituted with cysteine residues. In some embodiments, substituted residues occur at sites accessible to anti-MASP2 antibodies. By substituting cysteine for those residues, a reactive sulfhydryl group is located at an accessible site of the anti-MASP2 antibody and can be used to conjugate the anti-MASP2 antibody to other moieties, such as drug moieties or linker-drug moieties, to prepare anti-MASP2 immunoconjugates as further described herein. Cysteine-engineered anti-MASP2 antibodies (eg, full-length anti-MASP2 antibodies) can be prepared, eg, as described in U.S. Pat. No. 7,521,541.

derivative

In some embodiments, the anti-MASP2 antibodies provided herein (eg, full-length anti-MASP2 antibodies) can be further modified to include other non-protein moieties known in the art and readily available. Moieties suitable for derivatizing anti-MASP2 antibodies include, but are not limited to, water soluble polymers. Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), ethylene glycol/propylene glycol copolymers, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, poly-1 ,3-dioxolane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyamino acid (homopolymer or random copolymer), dextran or poly(n- vinylpyrrolidone) polyethylene glycol, propylene glycol homopolymer, propylene oxide/ethylene oxide copolymer, polyoxyethylated polyols (eg glycerol), polyvinyl alcohol and mixtures thereof. Polyethylene glycol propionaldehyde has advantages in manufacturing due to its stability in water. The polymers can be of any molecular weight and can be branched or unbranched. The number of polymers attached to the anti-MASP2 antibody can vary, and if more than one polymer is attached, they can be the same or different molecules. In general, the amount and/or type of polymers used for derivatization can be determined based on considerations including, but not limited to, the need to improve the properties or function of the anti-MASP2 antibody, whether an anti-MASP2 antibody derivative is useful for a particular condition treatment etc.

pharmaceutical composition

Also provided herein are compositions (e.g., pharmaceutical compositions) comprising any of an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a nucleic acid encoding an antibody, a vector comprising a nucleic acid encoding an antibody, or a host cell comprising a nucleic acid or vector described herein. substances, also referred to herein as preparations). In some embodiments, a pharmaceutical composition is provided, comprising any one of the anti-MASP2 antibodies described herein and a pharmaceutically acceptable carrier.

A suitable anti-MASP2 antibody can be obtained by mixing an anti-MASP2 antibody of desired purity with optionally a pharmaceutically acceptable carrier, excipient or stabilizer (Remington's Pharmaceutical Sciences 16th edition, Osol, A.Ed. (1980)). Antibody preparations are prepared in the form of freeze-dried preparations or liquid preparations. Acceptable carriers, excipients, or stabilizers that are nontoxic to recipients at the dosages and concentrations employed include buffers such as: phosphates, citric acid, and other organic acids; antioxidants, including ascorbic acid and methionine; preservatives such as Octadecyldimethylbenzylammonium chloride; Hexamethylammonium chloride; Benzalkonium chloride; Benzethonium chloride; Phenol; Butanol or benzyl alcohol; Alkylparabens such as p-hydroxybenzoate Methyl formate or propyl paraben; catechol; resorcinol; cyclohexanol; 3-pentanol and m-cresol); low molecular weight (less than 10 residues) polypeptides; proteins such as serum Albumin, gelatin, or immunoglobulin; hydrophilic polymers, such as polyvinylpyrrolidone; amino acids, such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides and other carbohydrates, including glucose, mannose or dextrin; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium; metal complexes such as zinc-protein complexes); and/or nonionic surfactants such as TWEEN ^™ , PLURONICS ^™ or polyethylene glycol (PEG); exemplary formulations are as described in WO98/56418, expressly incorporated herein by reference. Lyophilized formulations suitable for subcutaneous administration are described in WO97/04801. Such lyophilized formulations can be reconstituted with a suitable diluent into a high protein concentration formulation, and the reconstituted formulation can be administered subcutaneously to the individual to be treated herein. Cationic liposomes or liposomes can be used to deliver the anti-MASP2 antibodies of the present application to cells.

In addition to anti-MASP2 antibodies (such as full-length anti-MASP2 antibodies), the preparations described herein may also contain one or more other active substances necessary for the treatment of specific diseases, preferably substances with complementary activities and no adverse reactions to each other . For example, in addition to anti-MASP2 antibodies, it may be desirable to further include immunosuppressants, anti-inflammatory drugs, analgesics, other complement inhibitors, or vascular inhibitors. These molecules are present in combination in amounts effective for the intended purpose. Effective amounts of other substances depend on the amount of anti-MASP2 antibody in the formulation, the type of disease or disorder or treatment, and other factors as described above. These agents are generally used at the same doses and routes of administration as described herein, or at 1% to 99% of the currently employed doses.

The anti-MASP2 antibody (e.g., full-length anti-MASP2 antibody) can also be embedded in microcapsules prepared, e.g., by coacervation techniques and interfacial polymerization, e.g., in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, respectively). , microemulsions, nanoparticles and nanocapsules) or in macroemulsions of hydroxymethylcellulose or gelatin-microcapsules and poly(methyl methacrylate) microcapsules. Sustained release formulations can be prepared.

Sustained-release formulations of anti-MASP2 antibodies (eg, full-length anti-MASP2 antibodies) can be prepared. Suitable examples of sustained release formulations include semipermeable matrices of solid hydrophobic polymers containing the antibody (or fragment thereof) in the form of shaped articles, eg, films or microcapsules. Examples of sustained release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol)), polylactic acid (U.S. Pat. No. 3,773,919), L-glutamine Acid and ethyl L-glutamate copolymer, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymer such as LUPRON DEPOTTM (composed of lactic acid-glycolic acid copolymer and leuprolide acetate can injection microspheres) and poly-D(-)-3-hydroxybutyrate. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid can release molecules for more than 100 days, certain hydrogels can release proteins for a shorter period of time. When encapsulated antibodies stay in the body for a long time, they will denature or aggregate due to exposure to a humid environment at 37°C, which may lead to loss of biological activity or changes in immunogenicity. According to the corresponding mechanism, rational strategies can be designed to stabilize anti-MASP2 antibodies. For example, if the mechanism of aggregation is found to be the formation of intermolecular S-S bonds through thiodisulfide exchange, it may be possible to modify sulfhydryl residues, lyophilize in acidic solutions, control water content, use appropriate additives, and develop specific polymers. matrix composition for stabilization.

In some embodiments, the anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody) is formulated in the presence of citrate, sodium chloride, acetate, succinate, glycine, polysorbate 80 (Tween 80), or in any combination of the above buffers.

Preparations for in vivo administration must be sterile. This is readily accomplished, for example, by filtration using sterile filtration membranes.

Treatment using anti-MASP2 antibodies

Anti-MASP2 antibodies (e.g., full-length anti-MASP2 antibodies) and/or compositions described herein can be administered to individuals (e.g., mammals, such as humans) to treat diseases and/or conditions resulting from MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease, and/or viral infectious disease), including but not limited to ischemia-reperfusion injury, atherosclerosis, Mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemia glomerulonephritis, lupus nephritis, Henry Noch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis-induced acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune Thrombotic Thrombocytopenic Purpura (TTP), Hemolytic Uremic Syndrome (HUS), Atypical Hemolytic Uremic Syndrome (aHUS), Paroxysmal Nocturnal Hemoglobinuria (PNH), Transplant Secondary TMA, Upshaw -Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), disseminated intravascular coagulation (DIC), angiogenesis-dependent cancers, age-related macular degeneration, proliferative diabetic retinopathy , proliferative diabetic retinopathy secondary vitreous hemorrhage, neovascular glaucoma, corneal neovascularization, retinopathy of prematurity, and respiratory distress syndrome or pneumonia caused by coronavirus infection. Therefore, the present application, in some embodiments, provides a method for treating diseases and/or disorders caused by MASP2-dependent complement activation (for example, autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, angiogenesis-dependent diseases) and/or viral infectious diseases), comprising administering to an individual an effective amount of a composition (e.g., a pharmaceutical composition) comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), such as any of those described herein An anti-MASP2 antibody (eg, a full-length anti-MASP2 antibody), in some embodiments, the individual is a human.

In some embodiments, the coronavirus is SARS coronavirus (SARS-CoV) causing severe acute respiratory syndrome (SARS), MERS coronavirus (MERS-CoV) causing Middle East respiratory syndrome and/or causing 2019 Novel coronavirus SARS-CoV-2 of coronavirus disease (COVID-19).

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to the individual an effective amount of a pharmaceutical composition comprising a MASP2 antibody (e.g., a full-length anti-MASP2 antibody) that specifically binds to an epitope on human MASP2, wherein the The epitope comprises amino acid residues of human MASP2. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: heavy chain complementarity determining region (HC-CDR) 1 comprising SDYAWN (SEQ ID NO: 1); HC-CDR2 comprising YISYSGRTSYNPSLKS (SEQ ID NO: 5); and HC-CDR3 comprising Comprising HYGX ₁ X ₂ (SEQ ID NO: 38), wherein X ₁ is D or S, X ₂ is H or Y; and a light chain variable domain (V _L ), said V _L comprising: light chain complementarity determination Region (LC-CDR) 1, which comprises KASQNVGTNVA (SEQ ID NO: 19); LC-CDR2, which comprises SASYRYS (SEQ ID NO: 26); and LC-CDR3, which comprises X ₁ QYNSX ₂ X ₃ X ₄ ( SEQ ID NO:39), wherein X ₁ is H or Q, X ₂ is N or Y, X ₃ is L or P, X ₄ is L or T. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or virus infectious disease) individual method, comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises _a _VH comprising: HC-CDR1 comprising SEQ ID NO The amino acid sequence shown in: 1, HC-CDR2, it comprises the amino acid sequence shown in SEQ ID NO:5, and HC-CDR3, it comprises the amino acid sequence shown in any one of SEQ ID NOs:13-14, or the A variant of the V _H comprising up to about 5 amino acid substitutions in its HC-CDRs; and a V _L comprising: LC- _CDR1 comprising the amino acid sequence shown in SEQ ID NO: 19, LC- CDR2, which comprises the amino acid sequence shown in SEQ ID NO:26, and LC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:30-31, or the variant of the V _L , its LC- CDRs contain up to about 5 amino acid substitutions.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: V _H , the V _H comprising any of SEQ ID NOs: 40-47 A amino acid sequence as shown or a variant thereof, said variant having at least about 80% sequence identity to any of the amino acid sequences shown in SEQ ID NOs: 40-47; and V _L , said V _L comprising SEQ ID NOs: 40-47 The amino acid sequence set forth in any of ID NOs: 62-68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in any of SEQ ID NOs: 62-68.

In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises: _VH , said _VH comprising: HC-CDR1 comprising an amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:13, or a variant of said _VH comprising in its HC-CDRs A substitution of up to about 5 amino acids; and a _VL comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 , which comprises the amino acid sequence of SEQ ID NO: 30, or a variant of said _VL comprising up to about 5 amino acid substitutions in its LC-CDRs.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 40, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 40 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:62. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody described herein comprises _a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody described herein comprises _a _VH comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:64. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 42, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 42 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody described herein comprises _a _VH comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:64. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:64. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises: _VH , said _VH comprising: HC-CDR1 comprising an amino acid sequence SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 14, or a variant of said _VH comprising in its HC-CDRs A substitution of up to about 5 amino acids; and a _VL comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO: 19, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 , which comprises the amino acid sequence of SEQ ID NO: 31, or a variant of said _VL comprising up to about 5 amino acid substitutions in its LC-CDRs.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 44 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:65. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 46 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:66. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 46 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 46, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 46 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:15, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:20, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:27, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:32, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for individuals with viral infectious diseases), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:48 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:48; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:69 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:69.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:16, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO: 21, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 27, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 33, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for individuals with viral infectious diseases), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:49 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:49; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:70 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:70.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:17, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO: 19, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 26, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 31, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:50 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set _forth in SEQ ID NO:50; and a V _L comprising the amino acid sequence set forth in SEQ ID NO:71 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:71.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:34, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for individuals with viral infectious diseases), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:51 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:51; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:72 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:72.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:29, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:35, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:52 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:52; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:73 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:73.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:22, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:34, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or virus infectious disease) individual method, comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises: V _H , said V _H comprising the amino acid shown in SEQ ID NO:53 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:53; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:72 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:72.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO: 24, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO: 28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO: 34, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:54 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:54; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:74 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:74.

For example, in some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease and A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a pharmaceutical composition comprising an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), a heavy chain variable domain ( _VH ), The _VH comprises: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:18, or Variants of said _VH comprising up to about 5 amino acid substitutions in its HC-CDRs; and light chain variable domains ( _VL ), said _VL comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:23, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:28, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:36, or variants of said V _L , comprising at most about 5 amino acid substitutions. In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for individuals with viral infectious diseases), comprising administering to the individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein the antibody comprises: _VH , the _VH comprising the amino acid shown in SEQ ID NO:55 sequence or a variant thereof, said variant having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:55; and _a V _L comprising the amino acid sequence set forth in SEQ ID NO:75 or A variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:75.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or virus infectious disease) individual method, comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises _a _VH comprising: HC-CDR1 comprising SEQ ID NO The amino acid sequence shown in: 3, HC-CDR2, it comprises the amino acid sequence shown in SEQ ID NO:10, and HC-CDR3, it comprises the amino acid sequence shown in SEQ ID NO:18, or the variable of described _VH A body comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a V _L comprising: LC- _CDR1 comprising the amino acid sequence shown in SEQ ID NO: 25, LC-CDR2 comprising SEQ ID NO: 25 The amino acid sequence shown in ID NO: 28, and LC-CDR3, it comprises the amino acid sequence shown in SEQ ID NO: 37, or the variant of described V _L , its LC-CDRs comprise the substitution of up to about 5 amino acids . In some embodiments, the anti-MASP2 antibody is a full length antibody. In some embodiments, the full length anti-MASP2 antibody is an IgGl or IgG4 antibody. In some embodiments, the disease or condition is selected from, for example, ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous proliferative glomerulonephritis, Glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemic glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock, sepsis acute respiratory distress syndrome or systemic inflammatory response syndrome, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), atypical hemolytic Uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos disease (Degos disease), Disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal neovascularization, retina of prematurity Lesions and respiratory distress syndrome or pneumonia caused by coronavirus infection. In some embodiments, the individual is a human.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or virus infectious disease) individual method, comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises: V _H , said V _H comprising any of SEQ ID NOs: 56-61 A amino acid sequence as shown or a variant thereof, said variant having at least about 80% sequence identity to any of the amino acid sequences shown in SEQ ID NOs: 56-61; and V _L , said V _L comprising SEQ ID NOs: 56-61 The amino acid sequence set forth in any one of ID NOs: 76-79, or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in any one of SEQ ID NOs: 76-79.

In some embodiments, a method for treating a disease associated with MASP2-dependent complement activation (e.g., an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or A method for an individual with a viral infectious disease), comprising administering to said individual an effective amount of a composition comprising an anti-MASP2 antibody, wherein said antibody comprises: _VH , said _VH comprising: HC-CDR1 comprising an amino acid sequence SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant of said _VH comprising in its HC-CDRs A substitution of up to about 5 amino acids; and a _VL comprising: LC- _CDR1 comprising the amino acid sequence of SEQ ID NO:25, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:28, and LC-CDR3 , which comprises the amino acid sequence of SEQ ID NO: 37, or a variant of said _VL comprising up to about 5 amino acid substitutions in its LC-CDRs.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 56 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:76. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 57 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 58 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 59 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 60 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody described herein comprises _a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 57 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 58 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 59 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 60 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody described herein comprises _a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:78. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 57 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 58 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 59 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody _described herein comprises: a _VH comprising the amino acid sequence of SEQ ID NO: 60, or a variant thereof having at least about 80 degrees to the amino acid sequence of SEQ ID NO: 60 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, an anti-MASP2 antibody described herein comprises _a _VH comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80 % sequence identity; and _a _VL comprising the amino acid sequence of SEQ ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79. In some embodiments, the anti-MASP2 antibodies described herein are full-length anti-MASP2 antibodies comprising an IgGl or IgG4 constant region. In some embodiments, the IgG1 is human IgG1. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:80. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:81. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:82. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:83.

In some embodiments, the individual is a mammal (eg, a human, non-human primate, rat, mouse, cow, horse, pig, sheep, goat, dog, cat, etc.). In some embodiments, the individual is a human. In some embodiments, the individual is a clinical patient, a clinical trial volunteer, an experimental animal, or the like. In some embodiments, the individual is less than 60 years old (including, for example, less than 50, 40, 30, 25, 20, 15, or 10 years old). In some embodiments, the individual is greater than 60 years old (including, for example, greater than 70, 80, 90, or 100 years old). In some embodiments, the individual is diagnosed with or is genetically predisposed to one or more of the diseases or conditions described herein (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, Angiogenesis-dependent diseases and/or viral infectious diseases). In some embodiments, the individual has one or more risk factors associated with one or more diseases or conditions described herein.

In some embodiments, the application provides a method of delivering an anti-MASP2 antibody (e.g., any anti-MASP2 antibody described herein, e.g., an isolated anti-MASP2 antibody) to MASP2-dependent complement-activated cells in an individual, the The method comprises administering to the individual a composition comprising an anti-MASP2 antibody.

Many diagnostic methods for autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, angiogenesis-dependent diseases and/or viral infectious diseases or any other diseases showing association with MASP2-dependent complement activation and the methods of these diseases Clinical descriptions are known in the art. Such methods include, but are not limited to, eg, immunohistochemistry, ELISA, PCR, and fluorescence in situ hybridization (FISH).

In some embodiments, the anti-MASP2 antibodies described herein (e.g., full-length anti-MASP2 antibodies) and/or compositions are combined with a second, third, or fourth agent (including, for example, immunosuppressants, anti-inflammatory drugs, pain relievers, other complement inhibitors or vasopressors) to treat diseases associated with MASP2-dependent complement activation.

The therapeutic efficacy and appropriate dosage of a MASP-2 inhibitory composition of the invention for a particular subject can be determined according to complement assays well known to those skilled in the art. In the last decade, sensitive and accurate assays have been developed and most of these activation products are commercially available, including the small activation fragments C3a, C4a and C5a and the large activation fragments iC3b, C4d, Bb and MAC. Most of these assays rely on ELISA technology, although sometimes radioimmunoassays are still used for C3a and C5a. Radioimmunoassay measures the unprocessed fragment and its "des-Arg" fragment, which are the major forms present in circulation. Unprocessed fragments and C5a desArg are rapidly cleared by binding to cell surface receptors and are therefore present in very low concentrations. However, C3a de-Arg does not bind to cells and only accumulates in plasma. C3a provides a pathway-independent marker and is very sensitive to complement activation. Alternative pathway activation can be assessed by measuring the Bb fragment. Detection of MAC, the liquid-phase product of activation of the membrane attack pathway, provides evidence that complement is fully activated. The lectin pathway and the classical pathway will produce the same activation products C4a and C4d, but under specific experimental conditions, the activation of the lectin pathway or the classical pathway can still be detected.

Dosage and method of administration of anti-MASP2 antibody

Dosages of anti-MASP2 antibody (eg, isolated anti-MASP2 antibody) compositions administered to an individual (eg, a human) may vary depending on the particular composition, mode of administration, and type of disease being treated. In some embodiments, the amount of the composition (e.g., a composition comprising an anti-MASP2 antibody) can be adjusted in an autoimmune disease, an inflammatory disease, a blood disease, a coagulation disease, an angiogenesis-dependent disease, and/or a viral infectious disease. Effective in treating a disease to produce an objective response (eg, a partial response or a complete response). In some embodiments, the amount of anti-MASP2 antibody composition is sufficient to produce a complete response in an individual. In some embodiments, the amount of anti-MASP2 antibody composition is sufficient to produce a partial response in an individual. In some embodiments, the anti-MASP2 antibody composition is administered at a dose (e.g., when administered alone) sufficient to produce greater than 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85%, or 90% overall response rate. An individual's response to the treatment methods described herein can be determined, for example, by changes in components of the complement system.

In some embodiments, the amount of the composition (eg, a composition comprising an isolated anti-MASP2 antibody) is sufficient to prolong progression-free survival in the individual. In some embodiments, the amount of the composition is sufficient to prolong the overall survival of the subject. In some embodiments, the amount of the composition (eg, when administered alone) is sufficient to produce greater than 50%, 60%, 70%, or 77% clinical benefit in a population of individuals treated with an anti-MASP2 antibody composition.

In some embodiments, the amount of a composition (e.g., a composition comprising an isolated anti-MASP2 antibody), used alone or in combination with a second, third, and/or fourth agent, is that before treatment or with An amount sufficient to control symptoms and reduce the risk of exacerbations compared to corresponding activity in other subjects not receiving treatment. The magnitude of this therapeutic effect can be measured using standard methods, such as in vitro assays of purified enzymes, cell-based assays, animal models, or human trials.

In some embodiments, when the composition is administered to an individual, the amount of anti-MASP2 antibody (e.g., full-length anti-MASP2 antibody) in the composition is lower than that which causes a toxic effect (i.e., a level of toxicity above a clinically acceptable level). effect), or at a level at which potential side effects can be managed or tolerated.

In some embodiments, following the same dosing regimen, the amount of the composition approximates the maximum tolerated dose (MTD) of the composition. In some embodiments, the amount of the composition is greater than 80%, 90%, 95%, or 98% of the MTD.

In some embodiments, the amount of anti-MASP2 antibody (eg, full-length anti-MASP2 antibody) in the composition ranges from 0.001 μg to 1000 μg.

In any of the above embodiments, the effective amount of the anti-MASP2 antibody (eg full-length anti-MASP2 antibody) in the composition is in the range of 0.1 μg/kg to 100 mg/kg based on body weight.

Anti-MASP2 antibody compositions can be administered to an individual (e.g., a human) by a variety of routes, including, for example, intravenous injection, intraarterial administration, intraperitoneal injection, intrapulmonary administration, oral administration, inhalation administration, intravascular administration, Intramuscular, intratracheal, subcutaneous, intraocular, intrathecal, mucosal or transdermal. In some embodiments, sustained release formulations of the compositions are used. In some embodiments, the composition is administered intravenously. In some embodiments, the composition is administered arterially. In some embodiments, the composition is administered intraperitoneally. In some embodiments, the composition is administered intrahepatically. In some embodiments, the composition is administered by hepatic artery infusion. In some embodiments, the composition is administered at a site remote from the first lesion.

Products and kits

In some embodiments of the present application, there is provided an article of manufacture comprising a substance capable of being used in the treatment of diseases caused by MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis-dependent disease, and/or viral infectious disease), or for delivering an anti-MASP2 antibody (eg, a full-length anti-MASP2 antibody) to cells that are activated by MASP2-dependent complement. The article of manufacture may comprise a container and a label or package insert on or accompanying the container. Suitable containers include, for example, bottles, vials, syringes, and the like. Containers can be made of various materials such as glass or plastic. Typically, the container contains a composition effective to treat a disease or condition described herein and has a sterile port (eg, the container may be an IV bag or a vial with a hypodermic needle-pierceable cap). At least one active substance in the composition is the anti-MASP2 antibody described in this application. The label or package insert identifies the particular condition that the composition may be used to treat. The label or package insert further comprises instructions for administering the anti-MASP2 antibody composition to a patient. Articles of manufacture and kits comprising combination therapies are contemplated herein.

Package insert refers to the instructions commonly included in commercial packages of therapeutic products that contain indications, usage, dosage, administration, contraindications and/or warning information pertaining to the use of such therapeutic products. In some embodiments, the package insert indicates that the composition can be used to treat diseases caused by MASP2-dependent complement activation (such as autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, angiogenesis-dependent diseases, and/or viral infectious diseases). In some embodiments, the package insert indicates that the composition can be used to treat the following diseases, including ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis , membranous proliferative glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemia glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, Septic shock, acute respiratory distress syndrome or systemic inflammatory response syndrome caused by sepsis, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS ), atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation, Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), Degos Degos disease, disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma, corneal Neovascularization, retinopathy of prematurity, and respiratory distress syndrome or pneumonia due to coronavirus infection.

In addition, the article of manufacture may further comprise a second container comprising a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate buffered saline, Greene's solution, or dextrose solution. Other commercially and user-desired materials may also be included, including other buffers, diluents, filters, needles, and syringes.

It also relates to kits that can be used for various purposes, such as for the treatment of diseases associated with MASP2-dependent complement activation (such as autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, angiogenesis-dependent diseases and/or or viral infectious disease), or for delivering an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody) to cells expressing MASP2 on the surface, optionally in combination with a preparation. Kits of the present application include one or more containers comprising an anti-MASP2 antibody composition (or single dosage form and/or preparation) and, in some embodiments, further comprising another agent (e.g., an agent described herein ) and/or instructions for use consistent with any of the methods described herein. The kit may further include instructions for selecting an individual for treatment. The instructions for use attached to the kit in the present application are usually written instructions on the label or package insert (such as paper sheets included in the kit), machine-readable instructions (such as instructions on a magnetic or optical storage disc) is also acceptable.

For example, in some embodiments, the kit includes a composition comprising an anti-MASP2 antibody (eg, a full-length anti-MASP2 antibody). In some embodiments, the kit comprises: a) a composition comprising any one of the anti-MASP2 antibodies described herein, and b) at least one effective amount of another agent capable of enhancing the effect of the anti-MASP2 antibody (e.g., therapeutic effect, detection effect). In some embodiments, the kit comprises: a) a composition comprising any of the anti-MASP2 antibodies described herein, and b) administering the anti-MASP2 antibody composition to an individual for the treatment of a disease associated with MASP2-dependent complement activation (eg, autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, angiogenesis-dependent diseases and/or viral infectious diseases). In some embodiments, the kit comprises: a) a composition comprising any one of the anti-MASP2 antibodies described herein, and b) at least one effective amount of another agent capable of enhancing the effect of the anti-MASP2 antibody (e.g., therapeutic effect, detecting effect) and c) administering anti-MASP2 antibody compositions and other substances to individuals for the treatment of diseases associated with MASP2-dependent complement activation (e.g., autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, vascular Instructions for use of dependent diseases and/or viral infectious diseases). The anti-MASP2 antibody and other substances may be present in separate containers or in the same container. For example, the kit may include one particular composition or two or more compositions, where one composition includes an anti-MASP2 antibody and the other composition includes another agent.

In some embodiments, the kit comprises a nucleic acid (or a set) encoding an anti-MASP2 antibody (eg, a full-length anti-MASP2 antibody). In some embodiments, the kit comprises: a) a nucleic acid (or set of nucleic acids) encoding an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), and b) a host expressing the nucleic acid (or set of nucleic acids) cell. In some embodiments, the kit comprises: a) a (or set of) nucleic acid encoding an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), and b) instructions for use, suitable for: i) in a host cell expressing an anti-MASP2 antibody, ii) preparing a composition comprising the anti-MASP2 antibody, and iii) administering the composition comprising the anti-MASP2 antibody to an individual for the treatment of a disease associated with MASP2-dependent complement activation (e.g., autoimmune disease, inflammatory disease , blood disease, coagulation disease, angiogenesis-dependent disease and/or viral infectious disease). In some embodiments, the kit comprises: a) a (or set of) nucleic acid encoding an anti-MASP2 antibody (e.g., a full-length anti-MASP2 antibody), b) a host cell expressing the nucleic acid (or set of nucleic acids) , and c) instructions for use, suitable for: i) expressing the anti-MASP2 antibody in a host cell, ii) preparing a composition comprising the anti-MASP2 antibody, and iii) administering the composition comprising the anti-MASP2 antibody to an individual for the treatment of patients with MASP2 dependence Diseases associated with sexual complement activation (such as autoimmune diseases, inflammatory diseases, blood diseases, coagulation diseases, angiogenesis-dependent diseases and/or viral infectious diseases).

The kits described herein are packaged in a suitable form. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (eg, sealed mylar or plastic bags), and the like. Kits may optionally provide other components, such as buffers and instructional information. Accordingly, the present application also provides articles of manufacture including vials, bottles, jars, flexible packaging (eg, sealed mylar or plastic bags), and the like.

The instructions for use of the anti-MASP2 antibody composition usually include some information, such as dosage, administration cycle and administration route. The container can be unit dose, bulk (eg, multi-dose package) or subunit dose. For example, a kit comprising a sufficient dose of an anti-MASP2 antibody as described herein (e.g., a full-length anti-MASP2 antibody) is provided for long-term effective treatment of an individual, e.g., one week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months or longer time. Kits may also comprise multiple unit doses of anti-MASP2 antibody, pharmaceutical compositions and instructions for use, and be packaged in quantities sufficient for storage and use in pharmacies, eg, hospital pharmacies and compounding pharmacies.

Those skilled in the art will recognize several embodiments that are possible within the scope and spirit of the application. The present application will now be described in more detail by reference to the following non-limiting examples. The following examples further illustrate the present application but should not be construed as limiting its scope in any way.

Detailed ways

Embodiment 1: Preparation of recombinant protein

Preparation of recombinant full-length human MASP2 protein without self-cleavage activity

Upon binding to MBL, collagen lectins, or fibrogelins (collectively referred to as lectins), MASP2 forms dimers and is activated by self-cleavage. Self-cleavage of MASP2 often occurs during isolation of MASP2 from serum, or during purification after recombinant expression. In order to obtain high-yield and stable MASP2 antigen, the cDNA encoding human MASP2 protein (synthesized by Shanghai Jierui Bioengineering Co., Ltd.) was first constructed into a prokaryotic expression vector by subcloning. The 444th arginine residue in the protease domain (SP) was replaced by a glutamine residue by PCR site-directed mutagenesis to construct a full-length MASP2 mutant without self-cleavage activity, which was called MASP2 (R444Q). A His tag/or other tags commonly used by those skilled in the art were added to the C-terminus of the cDNA encoding human MASP2 (R444Q) protein to construct a tagged plasmid encoding human MASP2 (R444Q). The above tag plasmid was transformed into E. coli for expression to produce a MASP2 fusion protein without self-cleavage activity, such as MASP2(R444Q)-His, wherein "His" represents a His tag.

Preparation of recombinant human, cynomolgus monkey, and mouse MASP2-derived polypeptides:

The cDNA encoding the CCP1-CCP2-SP domain of human (GenBank ID: 10747), cynomolgus monkey (GenBank ID: 102131322) or mouse (GenBank ID: 17175) MASP2 was constructed by subcloning into eukaryotic expression in the carrier. Replace R444 in the human SP domain with Q444 by PCR site-directed mutagenesis, and replace R443 in the mouse or cynomolgus monkey SP domain with Q443 to construct a MASP2-derived polypeptide encoding human, mouse or cynomolgus monkey Plasmids, the above derived polypeptides are respectively referred to as CCP1-CCP2-SP(R444Q) of human MASP2, CCP1-CCP2-SP(R443Q) of cynomolgus MASP2 and CCP1-CCP2-SP(R443Q) of mouse MASP2. Add His tag and/or Avi tag and/or other tags commonly used by those skilled in the art at the end of the cDNA of the above-mentioned derived polypeptide to construct a tagged plasmid encoding the CCP1-CCP2-SP domain of MASP2 in humans, cynomolgus monkeys or mice . The above tagged plasmids were transfected into 293F cells for expression to produce fusion proteins of MASP2-derived polypeptides without self-cleavage activity, such as CCP1-CCP2-SP(R444Q)-His of human MASP2, CCP1-CCP2-SP(R444Q) of human MASP2 )-Avi-His, CCP1-CCP2-SP(R443Q)-His of cynomolgus monkey MASP2, CCP1-CCP2-SP(R443Q)-His of mouse MASP2, wherein, "His" represents His tag, "Avi" represents Avidin tag.

Preparation of recombinant human C1r, C1s protein

The cDNA encoding human C1r or C1s protein (synthesized by Shanghai Jierui Bioengineering Co., Ltd.) was constructed into a eukaryotic expression vector by subcloning. Add His tag and/or Avi tag and/or other tags commonly used by those skilled in the art at the end of the cDNA of the above-mentioned protein to construct a plasmid encoding human C1r or C1s protein. The above plasmids were transfected into 293F cells for expression to produce C1r or C1s fusion proteins, such as human C1r-His, human C1s-His, wherein "His" represents a His tag.

His-tagged recombinant proteins were purified using a nickel column (Ni) according to the manufacturer's instructions. The specific operation is as follows: Immobilized metal affinity chromatography (IMAC) is performed using Ni-NTA from QIAGEN Company. First, use buffer A1 (50mM Na ₃ PO ₄ , 0.15M NaCl, pH 7.2) to equilibrate the nickel column at a flow rate of 150cm/h, and transfer the solution containing the fusion protein (such as cell culture supernatant or E. coli lysate supernatant) to The pH was adjusted to 7.2, the sample was loaded at room temperature, and the flow rate was 150cm/h. Subsequently, the column was re-equilibrated with 6 column volumes of Al buffer at a flow rate of 150 cm/h. Finally, 10 column volumes of 50 mM PB solution (containing 0.15 M NaCl and 0.2 M imidazole, pH 7.2) were used for elution, and the eluate was collected.

Preparation of biotinylated human MASP2 antigen

According to the instruction manual, CP1-CCP2-SP(R444Q)-Avi-His of human MASP2 was biotinylated using biotinylated ligase B0101A (GeneCopoeia). Briefly, BufferA/B and BirA ligase were added to CCP1-CCP2-SP(R444Q)-Avi-His of human MASP2 and incubated at 30°C for 2 hours. Biotinylated CCP1-CCP2-SP(R444Q)-Avi-His of human MASP2 was named CCP1-CCP2-SP(R444Q)-Bavih of human MASP2. The biotinylation efficiency was detected by ELISA method, and it was determined that the biotinylation labeling efficiency of the above protein was at least 70%.

Example 2: Screening of single-chain antibodies (scFv) against MASP2

Construction of scFv antibody yeast display library:

Using CCP1-CCP2-SP(R444Q)-His of human MASP2 as antigen, immunize 6-8 week old BALB/c mice together with an equal volume (v/v) of adjuvant. The immunized mouse serum was taken, and the total IgG titer in the immunized mouse serum was detected by ELISA. After several rounds of immunizations, mouse spleens were used to establish phage display libraries. In short, the spleen of immunized mice was taken, RNA was extracted, cDNA was obtained by reverse transcription, V _H and V _K fragments were amplified with V _H and V _K specific primers, after gel recovery and purification, V _H and V were ligated _K , constructing scFv, and cloning it into the phage display plasmid pDAN3X, and then electrotransforming the plasmid into E. coli TG1, and using phage to infect E. coli TG1 to obtain the scFv antibody phage display library.

Screening of anti-MASP2 single chain antibody (scFv):

Phage that bound the CCP1-CCP2-SP domain of MASP2 were isolated from the phage display library using two screening strategies in multiple rounds of panning.

Solid-phase screening (Table 5): First, the human MASP2(R444Q)-His prepared in Example 1, the CCP1-CCP2-SP(R444Q)-His, C1s-His, and C1r-His antigens of human MASP2 were coated on the in an enzyme plate. Add the constructed phage display library to the MASP2 antigen-coated microtiter plate at an input amount of 4×10 ¹¹ pfu/well, and incubate at 37°C for 2 hours. Afterwards, positive phages that bind to the above two MASP2 antigens were screened out by using anti-M13 antibody (Sino Biological, 11973-MM05T-H), and the positive phages were eluted by alkaline eluent. In the second and subsequent rounds of screening, pre-screening against MASP2 functional analogs C1s/C1r (key enzymes of the classical complement pathway) was performed to remove phages that bind to C1s/C1r, and then screening was performed against MASP2 antigens. That is, first add the positive phage eluate to the enzyme plate coated with C1s-His and C1r-His antigens, and discard the phages that bind to C1s/C1r. Screening was carried out using the ELISA plates coated with human MASP2(R444Q)-His and CCP1-CCP2-SP(R444Q)-His of human MASP2. After multiple rounds of screening, positive phages binding to the above two MASP2 antigens were enriched. Through further ELISA detection, single positive clones were analyzed to obtain a series of positive scFv antibodies.

Table 5: Methods for solid-phase screening of phage display libraries

Liquid-phase screening (Table 6): CCP1-CCP2-SP(R444Q)-Bavih of human MASP2 prepared in Example 1 was mixed with the constructed phage display library (2×10 ¹² pfu), and incubated at 37°C for 1 hour. The mixture after the above incubation was added to the blocked streptavidin-coated magnetic beads, the positive phages combined with the above-mentioned MASP2 antigen were screened out, and the positive phages were eluted with alkaline eluent. In the second and subsequent rounds of screening, pre-screening against functional analogues C1s/C1r (key enzymes of the classical complement pathway) was first performed to remove phages that bind to C1s/C1r, and then screened against MASP2 antigen. That is, first add the positive phage eluate to the enzyme plate coated with C1s-His and C1r-His antigens, and discard the phages that bind to C1s/C1r. Screening was then performed using streptavidin-coated magnetic beads. After multiple rounds of screening, the positive phages binding to MASP2 antigen were enriched. Through further ELISA detection, single positive clones were analyzed to obtain a series of positive scFv antibodies.

Table 6: Liquid Phase Screening Methods for Phage Display Libraries

Example 3: Preparation and characterization of full-length chimeric antibodies against MASP2

Preparation of full-length chimeric antibody against MASP2

The positive scFv enriched after multiple rounds of screening were sequenced, V _L and V _H were amplified from the phage display vector, and constructed into eukaryotic expression vectors pTTa1-L (containing human κ constant region) and pTT5-H1 (containing human κ constant region) respectively. IgG1 heavy chain constant region) or pTTa1-H4 (comprising human IgG4 heavy chain constant region). The plasmid expressing the light chain and the plasmid expressing the heavy chain were co-transfected into 293F cells, cultured at 37° C., 8% CO ₂ , 120 rpm for 5 days, and the culture solution was purified by Protein A affinity chromatography. Briefly, the protein A column was first equilibrated with 6 column volumes of 50 mM PBS buffer (containing 0.15M NaCl, pH 7.2) at a flow rate of 150 cm/h. The culture supernatant (adjusted to pH 7.2) was passed through the column at a flow rate of 150 cm/h. After the column was further equilibrated, 50 mM sodium citrate buffer (pH 3.5) was used for elution, the eluate was collected, and the pH value was adjusted to neutral. The IgG solution was replaced in PBS buffer using a desalting column, and the antibody concentration was determined after concentration by ultrafiltration.

Affinity of anti-MASP2 chimeric antibody

The purified monoclonal antibody (reconstituted into human IgG4 form) was subjected to a binding assay with MASP2, which was used to identify the binding activity of the anti-MASP2 antibody. Briefly, human MASP2(R444Q)-His antigen was dissolved in PBS solution, coated with 0.1 μg/well of 96-well plate, and left overnight at 4°C. Block with 5% milk at 37°C for 1 hour, and wash 6 times with TBST solution. Each antibody sample was first diluted to 10 μg/ml, followed by a 1:3 serial dilution. The samples after serial dilution were added to 96-well plates, 100 μl per well, and incubated at 37° C. for 1 hour. It was subsequently washed 6 times with TBST solution. Add 100 μl of secondary antibody (goat anti-human IgG-HRP (1:10000)) to each well, and incubate at 37°C for 1 hour. Wash 6 times with TBST solution. Add 100 μl TMB to each well, incubate at 37°C for 10-20 minutes, and stop the reaction with 2M H ₂ SO ₄ . Read the absorbance at 450 nm with a microplate reader. Binding curves were generated by PRISM, EC ₅₀ values were calculated, and the affinity of each anti-MASP2 antibody to the antigen was analyzed based on this.

The results are shown in Table 7. A total of 11 anti-MASP2 antibodies with better affinity than the control antibody OMS721 were screened out. .

Table 7: Binding ability of anti-MASP2 chimeric antibodies to human MASP2

Cross-reactivity of anti-MASP2 chimeric antibodies

The screened anti-MASP2 antibody (reconstructed into human IgG4 format) was subjected to binding experiments with cynomolgus monkey and mouse MASP2 to identify the cross-reactivity of anti-MASP2 antibody with cynomolgus monkey or mouse MASP2 antigen. Briefly, CCP1-CCP2-SP(R444Q)-His of human MASP2, CCP1-CCP2-SP(R443Q)-His of cynomolgus MASP2 or CCP1-CCP2-SP(R443Q)-His of mouse MASP2 Dissolve in PBS solution, coat a 96-well plate at 0.1 μg/well, overnight at 4°C. Block with 5% milk at 37°C for 1 hour, and wash 6 times with TBST solution. Each antibody sample was first diluted to 10 μg/ml, followed by a 1:3 serial dilution. The samples after serial dilution were added to 96-well plates, 100 μl per well, and incubated at 37° C. for 1 hour. It was subsequently washed 6 times with TBST solution. Add 100 μl of secondary antibody (goat anti-human IgG-HRP (1:10000)) to each well, and incubate at 37°C for 1 hour. Wash 6 times with TBST solution. Add 100 μl TMB to each well, incubate at 37°C for 10-20 minutes, and stop the reaction with 2M H ₂ SO ₄ . Read the absorbance at 450 nm using a microplate reader. Binding curves were generated by PRISM, EC ₅₀ values were calculated, and the affinity of each anti-MASP2 antibody to cynomolgus or mouse antigen was analyzed.

The results are shown in Table 8. All the screened anti-MASP2 antibodies have good binding ability to human MASP2 antigen; Antigens all have cross-binding activity; anti-MASP2 antibodies M2mc62, M2mc69 have no cross-binding ability to mouse MASP2 antigen, M2mc12, M2mc51 and M2mc56 have slightly weaker cross-binding ability to mouse MASP2 antigen, and the remaining 6 candidate antibodies have cross-binding ability to mouse antigen Good cross-binding activity.

Table 8: Cross-binding ability of anti-MASP2 chimeric antibodies to MASP2 from other species

Detection of complement lectin pathway activity by anti-MASP2 antibody:

Mannan is a known activator of the lectin pathway, which can bind to MBL to activate the lectin pathway of complement. After the complement lectin pathway is activated, the proteolytic activity of MASP2 cleaves its substrate complement molecule C4 into C4a and C4b, and C2 into C2a and C2b, wherein C4b and C2a further form C3 convertase (C4b2a). C3 convertase is one of the important central regulatory molecules in the complement system, which cuts the complement molecule C3 into two strong pro-inflammatory molecules: anaphylatoxin C3a and opsonizing molecule C3b, and C3b further combines with C4b2a to form C5 convertase ( C4b2a3b). C5 convertase is another important central regulatory molecule in the complement system. Its hydrolase activity cleaves C5 into anaphylatoxins C5a and C5b, and finally C5b and C6-9 form the membrane attack complex MAC (C5b-9). C3b, C4b, and MAC (C5b-9) all contain highly reactive thioester groups that can form covalent bonds with hydroxyl or amino groups on macromolecules immobilized by ester or amide bonds at the bottom of plastic wells , so that C3b, C4b and MAC (C5b-9) can be deposited on the bottom of the plastic microplate, so the deposition of the above molecules can be detected by ELISA method.

Based on the above principles, the ELISA method was used to detect the complement molecules C3b, C4b and MAC deposited in human plasma to reflect the biological activity of the anti-MASP2 antibody in the lectin pathway. There are three methods for detecting the activity of anti-MASP2 antibody: (1) ELISA is used to detect the deposition level of C4b to reflect the activity of anti-MASP2 antibody to inhibit MASP2 from cleaving its direct substrate C4; (2) ELISA is used to detect the deposition level of C3b, To reflect the activity of the anti-MASP2 antibody in inhibiting the formation of C3 convertase in the lectin pathway; (3) ELISA was used to detect the deposition level of MAC to reflect the activity of the anti-MASP2 antibody in inhibiting the formation of the biological effector molecule MAC in the lectin pathway.

Mannan (Sigma, M7504) was diluted to 100 μg/ml with alkaline coating buffer (15 mM Na ₂ CO ₃ , 35 mM NaHCO ₃ , pH 9.8), coated with 100 μl per well, and kept overnight at 4°C. The next day, wash 3 times with PBST buffer. Add 100 μl of blocking solution (1% human serum albumin HSA) to each well and incubate at 37° C. for 1 hour. Wash 3 times with PBST buffer. Normal human plasma was diluted to 2% in Ca ²⁺ , Mg ²⁺ buffer (10 mM Tris-HCl, 150 mM NaCl, 0.5 mM MgCl ₂ , 2 mM CaCl ₂ , 0.1% gelatin, 0.05% Tween-20, pH 7.4). The anti-MASP2 antibody (reconstituted into human IgG4 format) with an initial concentration of 100 μg/ml was serially diluted at a ratio of 1:6 with Ca ²⁺ , Mg ²⁺ buffer. Equal volumes of diluted plasma and anti-MASP2 antibody were mixed (the final concentration of human plasma in the reaction system was 1%, and the maximum final concentration of anti-MASP2 antibody was 50 μg/ml), and incubated at 37°C for 2 hours. The wells were washed with PBST buffer to terminate the reaction. Add different detection antibodies to the above sample wells to detect the deposition of C3b, C4b or MAC.

(1) ELISA method to detect the deposition level of C4b: chicken anti-human C4b antibody (Abcam, ab48582) was added as a capture antibody, and goat anti-chicken antibody (Southern Biotech, 6100-05) was used as a detection antibody to detect C4b deposition in human plasma. The absorbance value at 450nm was read with a microplate reader, and the binding curve was generated by Graphpad Prism, and the _IC50 value was calculated.

The results are shown in Table 9. Compared with the control antibody OMS721, the activities of M2mc7 and M2mc10 in inhibiting C4b deposition are comparable. However, the IC ₅₀ values of M2mc12, M2mc51, M2mc56, M2mc60, M2mc63, M2mc65, and M2mc67 were significantly lower than those of the control antibody OMS721 (about 43-160 times), indicating that M2mc12, M2mc51, M2mc56, M2mc60, M2mc63, M2mc65, and M2mc 67 with good suppression The activity of C4b deposition in human plasma, and its function of inhibiting lectin pathway activity is better than that of the control antibody OMS721.

Table 9: Inhibition of C4b activity by anti-MASP2 chimeric antibodies

(2) ELISA method was used to detect the deposition level of C3b: mouse anti-human C3b antibody (abcam, ab231078) was added as a capture antibody, and rabbit anti-mouse antibody (Sigma, A9044) was used as a detection antibody to detect C3b deposition in human plasma. The absorbance value at 450nm was read with a microplate reader, and the binding curve was generated by Graphpad Prism, and the _IC50 value was calculated.

The results are shown in Table 10. The _IC50 values of anti-MASP2 antibodies M2mc12, M2mc51, M2mc63 and M2mc67 for inhibiting C3b deposition in human plasma were significantly lower than those of the control antibody OMS721 (about 6-40 times), indicating that M2mc12, M2mc51, M2mc63 or M2mc67 have good The activity of inhibiting C3b deposition in human plasma, and its function of inhibiting the activity of lectin pathway is better than that of the control antibody OMS721.

Table 10: Anti-MASP2 chimeric antibodies inhibit C3b activity

(3) ELISA method was used to detect the deposition level of MAC: rabbit anti-human MAC antibody (Merck, 204903) was added as a capture antibody, and goat anti-rabbit antibody (Life, 656120) was used as a detection antibody to detect MAC deposition in human plasma. The absorbance value at 450nm was read with a microplate reader, and the binding curve was generated by Graphpad Prism, and the _IC50 value was calculated.

The results are shown in Table 11. The IC ₅₀ values of anti-MASP2 antibodies M2mc12, M2mc51, M2mc63 and M2mc67 in inhibiting MAC deposition in human plasma were significantly lower than those of the control antibody OMS721 (about 17-110 times), indicating that M2mc12, M2mc51, M2mc63 or M2mc67 can be compared with Good inhibits MAC deposition in human plasma, and its function of inhibiting lectin pathway activity is superior to that of the control antibody OMS721.

Table 11: Inhibition of MAC activity by anti-MASP2 chimeric antibodies

Example 4: Humanization of anti-MASP2 antibodies and characterization of humanized antibodies

Based on the typical structures of the light chain and heavy chain variable region CDRs of the obtained mouse antibodies M2mc12, M2mc51 or M2mc67, the light chain and heavy chain variable region sequences were compared with the sequences in the antibody germline database to obtain the same Highly derived human germline template. The CDR regions of mouse antibodies are grafted onto selected human germline templates to generate humanized variable regions, which are then recombined with corresponding human IgG constant regions (preferably IgG4 heavy chain and kappa light chain). Based on the three-dimensional structure of the mouse antibody, carry out complementary mutations on the buried residues, the residues that directly interact with the CDR region, and the residues that have an important impact on the conformation of VL _{and VH} _, and design different light Chain, heavy chain, and combined to obtain a series of humanized molecules. Finally, 6 humanized antibodies to M2mc12 (humM2mc12), 9 humanized antibodies to M2mc51 (humM2mc51), and 15 humanized antibodies to M2mc67 (humM2mc67) were obtained.

Detection of complement lectin pathway activity by anti-MASP2 antibody:

The experimental method described in Example 3 was used to detect the biological activity of the humanized anti-MASP2 antibody (reconstructed into human IgG4 form) in the lectin pathway, that is, the deposition levels of C4b, C3b and MAC were detected by ELISA method.

The results are shown in Table 12, the M2mc12 humanized antibodies humM2mc12-1, humM2mc12-2, humM2mc12-6, humM2mc12-7, humM2mc12-11 or humM2mc12-12 have a good function of inhibiting the activity of the lectin pathway. Compared with the chimeric antibody M2mc12, humM2mc12-1, humM2mc12-2, humM2mc12-6, humM2mc12-7, humM2mc12-11 or humM2mc12-12 had a slightly increased or equivalent inhibitory activity on human plasma C3b or MAC deposition, and inhibited human The activity of plasma C4b deposition was equal or slightly lower.

Table 12: Inhibitory lectin pathway activity of M2mc12 humanized antibodies

The results are shown in Table 13. The M2mc51 humanized antibodies humM2mc51-1~humM2mc51-9 all have a good function of inhibiting the activity of the lectin pathway, and any antibody among humM2mc51-1~humM2mc51-9 inhibits human plasma C4b, C3b and The activity of MAC deposition was comparable to that of chimeric antibody M2mc51.

Table 13: Inhibitory lectin pathway activity of M2mc51 humanized antibodies

The results are shown in Table 14. The M2mc67 humanized antibodies humM2mc67-1~humM2mc67-15 all have a good function of inhibiting the activity of the lectin pathway, and any antibody among humM2mc67-1~humM2mc67-15 inhibits human plasma C4b, C3b and The activity of MAC deposition was comparable to that of the chimeric antibody M2mc67.

Table 14: Lectin pathway inhibitory activity of M2mc67 humanized antibodies

Anti-MASP2 antibody affinity detection

Humanized antibodies humM2mc12-11, humM2mc51-1 and humM2mc67-9 were selected for affinity detection. Biacore 8K (GE) was used to characterize the binding affinity of the humanized antibody to human MASP2 and cynomolgus MASP2. In short, the humanized antibody humM2mc12-11, humM2mc51-1 or humM2mc67-9 was serially diluted, immobilized on the sensor chip CM5, and the anti-MASP2 antibody and human MASP2 CCP1-CCP2-SP(R444Q )-His or the affinity of the CCP1-CCP2-SP(R443Q)-His antigen of cynomolgus MASP2, the on-rate and off-rate of the antibody were measured by SPR technique, and the binding affinity was determined.

The results are shown in Table 15. The humanized antibodies humM2mc12-11, humM2mc51-1 or humM2mc67-9 can all bind to the CCP1-CCP2-SP domain of human and cynomolgus monkey MASP2, and their binding affinities are on the order of 10 ^-9 M ~ ^10-11 M.

Table 15: Affinities of Anti-MASP2 Antibodies

Detection of cross-reactivity of humanized anti-MASP2 antibodies

In order to detect whether the humanized anti-MASP2 antibody (reconstructed into human IgG4 form) can inhibit the lectin pathway of the monkey complement system, the C4b deposition experiment scheme in Example 3 was used to conduct the deposition of the complement component C4b in the monkey plasma. detection.

The results are shown in FIG. 1 , compared with the control antibody OMS721, the humanized anti-MASP2 antibodies humM2mc51-1 and humM2mc67-9 showed good activity of inhibiting C4b deposition. The results showed that humM2mc51-1 and humM2mc67-9 had cross-reactivity with monkey MASP2 and could inhibit the lectin pathway of monkey complement system.

Example 5: Pharmacokinetics of Anti-MASP2 Antibodies

Eighteen SD rats were randomly divided into three groups, 6 in each group, half male and half male. Rats in each group were intravenously injected with 10 mpk of anti-MASP2 antibodies humM2mc51-1, humM2mc67-9 or control antibody OMS721. Blood was first collected before antibody injection, and then blood was collected sequentially at 5min, 1h, 5h, 1d, 3d, 6d, 10d, 14d, and 17d after antibody injection. After the blood was centrifuged, the plasma was collected, and the antibody concentration in each sample was detected by ELISA method. use

Software version 6.0, pharmacokinetic parameters determined by non-compartmental model (NCA). All PK parameters, including maximum serum concentration (Cmax), half-life (T _1/2 ), apparent volume of distribution (Vd), Clearance (Cl) and area under the curve (AUClast) from the time of dosing to the last measurable concentration.

During the experiment, no abnormal clinical manifestations related to administration were seen. The experimental results are shown in Figure 2 and Table 16, the plasma drug concentrations of the humanized anti-MASP2 antibodies humM2mc12-11, humM2mc51-1, and humM2mc67-9 have basically the same trend over time.

Table 16: Pharmacokinetic indicators of anti-MASP2 antibody

T1 _/2 : terminal half-life; Cmax: maximum serum concentration; Tmax: time of Cmax; AUClast: area under the curve from the time of administration to the last measurable concentration; Vd: apparent volume of distribution; Cl: clearance rate.

Example 6: Anti-MASP2 Antibodies Inhibit Cynomolgus Complement Lectin Activity

Eight female cynomolgus monkeys were randomly divided into 3 groups, with 3 monkeys in each group in the experimental group and 2 monkeys in each group in the control group. The cynomolgus monkeys in the experimental group were intravenously injected with anti-MASP2 antibodies (taking humM2mc67-9 and humM2mc51-1 as examples), and the cynomolgus monkeys in the control group were injected with the control antibody OMS721 intravenously. The dosage was 5 mg/kg, and the dosage was 2ml /kg, the injection speed is about 3-4ml/min. The day of administration was recorded as day 0, and plasma was collected before administration and on

days

1, 4, 7, and 10 after administration, and the experimental method described in Example 3 was used to detect serum levels in cynomolgus monkeys after administration. The biological activity of the complement lectin pathway, that is, the deposition levels of C4b, C3b and MAC were detected by ELISA method.

The results are shown in Figure 3A, the inhibition rate of anti-MASP2 antibodies humM2mc67-9 and humM2mc51-1 on the formation of C4b reached the peak at 1 day of administration, and basically returned to the normal level at 4 days of administration. The results are shown in Figures 3B-3C, the inhibition of the formation of C3b (Figure 3B) or MAC (Figure 3C) by the anti-MASP2 antibodies humM2mc67-9 and humM2mc51-1 reached a peak at 7 days of administration, and returned to normal levels at 10 days of administration . The above results show that the anti-MASP2 antibody of the present invention has obvious inhibitory activity on the complement lectin pathway in vivo.

Claims

An isolated antibody that specifically recognizes MASP2, wherein the antibody comprises:

A heavy chain variable domain ( VH ), said VH comprising:

Heavy chain complementarity determining region (HC-CDR) 1, which comprises SDYAWN (SEQ ID NO: 1);

HC-CDR2 comprising YISYSGRTSYNPSLKS (SEQ ID NO:5); and

HC-CDR3, which comprises HYGX 1 X 2 (SEQ ID NO:38), wherein X 1 is D or S, and X 2 is H or Y;

and a light chain variable domain (V L ), said V L comprising:

Light chain complementarity determining region (LC-CDR) 1 comprising KASQNVGTNVA (SEQ ID NO: 19);

LC-CDR2 comprising SASYRYS (SEQ ID NO:26); and

LC-CDR3 comprising X 1 QYNSX 2 X 3 X 4 (SEQ ID NO:39), wherein X 1 is H or Q, X 2 is N or Y, X 3 is L or P, X 4 is L or T .
An isolated antibody specifically recognizing MASP2 comprising:

V H , said V H comprises:

HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:1;

HC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:5; and

HC-CDR3 comprising the amino acid sequence shown in any of SEQ ID NOs: 13-14 or a variant thereof comprising a substitution of up to about 3 amino acids;

and V L , the V L comprising:

LC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:19;

LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO: 26; and

LC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 30-31 or a variant thereof comprising a substitution of up to about 3 amino acids.
An isolated antibody specifically recognizing MASP2 , which comprises a VH comprising HC-CDR1, HC-CDR2 and HC contained in the VH as shown in any one of the amino acid sequences of SEQ ID NOs: 40 or 44 -CDR3; and VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 contained in the VL as shown in any one of the amino acid sequences of SEQ ID NOs:62 or 65.
The isolated antibody specifically recognizing MASP2 according to claim 3, comprising:

(i) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:40; and V L comprising the amino acid sequence of SEQ ID NO:62 LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the indicated VL ; or

(ii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:44; and V L comprising the amino acid sequence of SEQ ID NO:65 The indicated VL contains LC-CDR1, LC-CDR2 and LC-CDR3.
The isolated antibody specifically recognizing MASP2 according to any one of claims 1-4, comprising:

(i) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5 ID NO: 13, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 19. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 30, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions; or

(ii) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:1 ID NO: 14, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 19. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant of said V L comprising at most about 5 of its LC-CDRs Amino acid substitutions.
The isolated antibody specifically recognizing MASP2 according to any one of claims 1-5, comprising:

V H comprising the amino acid sequence shown in any of SEQ ID NOs: 40-47 or a variant thereof having at least about 80% of the amino acid sequence shown in any of SEQ ID NOs: 40-47 Sequence identity; And VL , it comprises the aminoacid sequence shown in any one of SEQ ID NOs:62-68 or its variant, described variant and the aminoacid sequence shown in any one of SEQ ID NOs:62-68 have at least about 80% sequence identity.
The isolated antibody specifically recognizing MASP2 according to claim 6, comprising:

(i) V H comprising the amino acid sequence of SEQ ID NO: 40 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 40; and V L comprising the amino acid sequence of SEQ ID NO: 40; ID NO:62 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:62;

(ii) V H comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 41; and V L comprising the amino acid sequence of SEQ ID NO: 41; ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63;

(iii) V H comprising the amino acid sequence of SEQ ID NO: 41 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 41; and V L comprising the amino acid sequence of SEQ ID NO: 41; ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:64;

(iv) V H comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 42; and V L comprising the amino acid sequence of SEQ ID NO: 42; ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63;

(v) V H comprising the amino acid sequence of SEQ ID NO: 42 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 42; and V L comprising the amino acid sequence of SEQ ID NO: 42; ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:64;

(vi) V H comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 43; and V L comprising the amino acid sequence of SEQ ID NO: 43; ID NO:63 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:63;

(vii) V H comprising the amino acid sequence of SEQ ID NO: 43 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 43; and V L comprising the amino acid sequence of SEQ ID NO: 43; ID NO:64 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:64;

(viii) V H comprising the amino acid sequence of SEQ ID NO: 44 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 44; and V L comprising the amino acid sequence of SEQ ID NO: 44; ID NO:65 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:65;

(ix) V H comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 45; and V L comprising the amino acid sequence of SEQ ID NO: 45; ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:66;

(x) V H comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 46; and V L comprising the amino acid sequence of SEQ ID NO: 46; ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:66;

(xi) V H comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 47; and V L comprising the amino acid sequence of SEQ ID NO: 47; ID NO:66 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:66;

(xii) V H comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 45; and V L comprising the amino acid sequence of SEQ ID NO: 45; ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67;

(xiii) V H comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 46; and V L comprising the amino acid sequence of SEQ ID NO: 46; ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67;

(xiv) V H comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 47; and V L comprising the amino acid sequence of SEQ ID NO: 47; ID NO:67 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:67;

(xv) V H comprising the amino acid sequence of SEQ ID NO: 45 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 45; and V L comprising the amino acid sequence of SEQ ID NO: 45; ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:68;

(xvi) V H comprising the amino acid sequence of SEQ ID NO: 46 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 46; and V L comprising the amino acid sequence of SEQ ID NO: 46; ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence SEQ ID NO:68; or

(xvii) V H comprising the amino acid sequence of SEQ ID NO: 47 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 47; and V L comprising the amino acid sequence of SEQ ID NO: 47; ID NO:68 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:68.
An isolated antibody specifically recognizing MASP2 comprising:

(i) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:48; and V L comprising the amino acid sequence of SEQ ID NO:69 LC-CDR1, LC-CDR2 and LC-CDR3 contained in the indicated VL ;

(ii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:49; and V L comprising the amino acid sequence of SEQ ID NO:70 LC-CDR1, LC-CDR2 and LC-CDR3 contained in the indicated VL ;

(iii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:50; and V L comprising the amino acid sequence of SEQ ID NO:71 LC-CDR1, LC-CDR2 and LC-CDR3 contained in the indicated VL ;

(iv) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:51; and V L comprising the amino acid sequence of SEQ ID NO:72 LC-CDR1, LC-CDR2 and LC-CDR3 contained in the indicated VL ;

(v) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:52; and V L comprising the amino acid sequence of SEQ ID NO:73 LC-CDR1, LC-CDR2 and LC-CDR3 contained in the indicated VL ;

(vi) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:53; and V L comprising the amino acid sequence of SEQ ID NO:72 LC-CDR1, LC-CDR2 and LC-CDR3 contained in the indicated VL ;

(vii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:54; and V L comprising the amino acid sequence of SEQ ID NO:74 LC-CDR1, LC-CDR2 and LC-CDR3 comprised by the indicated VL ; or

(viii) V H comprising HC-CDR1, HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:55; and V L comprising the amino acid sequence of SEQ ID NO:75 The indicated VL contains LC-CDR1, LC-CDR2 and LC-CDR3.
An isolated antibody specifically recognizing MASP2 comprising:

(i) V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:6, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:6 ID NO: 15, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 20. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 32, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions;

(ii) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:7 ID NO: 16, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 21. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 33, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions;

(iii) V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 5, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 5 ID NO: 17, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 19. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 31, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions;

(iv) V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:8 ID NO: 18, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 22. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions;

(v) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO:9 ID NO: 18, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 23. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions;

(vi) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 10 ID NO: 18, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 22. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions;

(vii) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 11 ID NO: 18, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 24. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or a variant of said V L comprising at most about 5 of its LC-CDRs amino acid substitutions; or

(viii) VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 12 ID NO: 18, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence SEQ ID NO: 23. LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or a variant of said V L comprising at most about 5 of its LC-CDRs Amino acid substitutions.
The isolated antibody specifically recognizing MASP2 according to claim 8 or 9, comprising:

(i) VH comprising the amino acid sequence set forth in SEQ ID NO:48 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:48; and VL , which comprises the amino acid sequence shown in SEQ ID NO: 69 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 69;

(ii) VH comprising the amino acid sequence set forth in SEQ ID NO:49 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:49; and VL , which comprises the amino acid sequence shown in SEQ ID NO: 70 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 70;

(iii) VH comprising the amino acid sequence set forth in SEQ ID NO:50 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:50; and VL , which comprises the amino acid sequence shown in SEQ ID NO: 71 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 71;

(iv) VH comprising the amino acid sequence set forth in SEQ ID NO:51 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:51; and VL , which comprises the amino acid sequence shown in SEQ ID NO: 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 72;

(v) VH comprising the amino acid sequence set forth in SEQ ID NO:52 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:52; and VL , which comprises the amino acid sequence shown in SEQ ID NO: 73 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 73;

(vi) VH comprising the amino acid sequence set forth in SEQ ID NO:53 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:53; and VL , which comprises the amino acid sequence shown in SEQ ID NO: 72 or a variant thereof having at least about 80% sequence identity to the amino acid sequence shown in SEQ ID NO: 72;

(vii) VH comprising the amino acid sequence set forth in SEQ ID NO:54 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:54; and VL , which comprises the amino acid sequence set forth in SEQ ID NO: 74 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO: 74; or

(viii) VH comprising the amino acid sequence set forth in SEQ ID NO:55 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:55; and VL , which comprises the amino acid sequence set forth in SEQ ID NO:75 or a variant thereof having at least about 80% sequence identity to the amino acid sequence set forth in SEQ ID NO:75.
An isolated antibody specifically recognizing MASP2 comprising:

V H , which comprises HC-CDR1 , HC-CDR2 and HC-CDR3 contained in V H as shown in the amino acid sequence of SEQ ID NO:56; and V L , which comprises the V shown in the amino acid sequence of SEQ ID NO:76 L contains LC-CDR1, LC-CDR2 and LC-CDR3.
An isolated antibody specifically recognizing MASP2 comprising:

V H , said V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 18, or a variant of said VH comprising a substitution of up to about 5 amino acids in its HC-CDRs; and a VL comprising: LC- CDR1 comprising the amino acid sequence of SEQ ID NO: 25, LC - CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or a variant of said VL comprising a substitution of up to about 5 amino acids in its LC-CDRs .
The isolated antibody specifically recognizing MASP2 according to claim 11 or 12, comprising:

(i) V H comprising the amino acid sequence of SEQ ID NO: 56 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 56; and V L comprising the amino acid sequence of SEQ ID NO: 56; ID NO: 76 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 76;

(ii) V H comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 57; and V L comprising the amino acid sequence of SEQ ID NO: 57; ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77;

(iii) V H comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 58; and V L comprising the amino acid sequence of SEQ ID NO: 58; ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77;

(iv) V H comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 59; and V L comprising the amino acid sequence of SEQ ID NO: 59; ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77;

(v) V H comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 60; and V L comprising the amino acid sequence of SEQ ID NO: 60; ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77;

(vi) V H comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; and V L comprising the amino acid sequence of SEQ ID NO: 61; ID NO:77 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:77;

(vii) V H comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 57; and V L comprising the amino acid sequence of SEQ ID NO: 57; ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78;

(viii) V H comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 58; and V L comprising the amino acid sequence of SEQ ID NO: 58; ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78;

(ix) V H comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 59; and V L comprising the amino acid sequence of SEQ ID NO: 59; ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78;

(x) V H comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 60; and V L comprising the amino acid sequence of SEQ ID NO: 60; ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78;

(xi) V H comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; and V L comprising the amino acid sequence of SEQ ID NO: 61; ID NO: 78 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 78;

(xii) V H comprising the amino acid sequence of SEQ ID NO: 57 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 57; and V L comprising the amino acid sequence of SEQ ID NO: 57; ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79;

(xiii) V H comprising the amino acid sequence of SEQ ID NO: 58 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 58; and V L comprising the amino acid sequence of SEQ ID NO: 58; ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79;

(xiv) V H comprising the amino acid sequence of SEQ ID NO: 59 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 59; and V L comprising the amino acid sequence of SEQ ID NO: 59; ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79;

(xv) V H comprising the amino acid sequence of SEQ ID NO: 60 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 60; and V L comprising the amino acid sequence of SEQ ID NO: 60; ID NO: 79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 79; or

(xvi) V H comprising the amino acid sequence of SEQ ID NO: 61 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO: 61; and V L comprising the amino acid sequence of SEQ ID NO: 61; ID NO:79 or a variant thereof having at least about 80% sequence identity to the amino acid sequence of SEQ ID NO:79.
The isolated antibody specifically recognizing MASP2 according to any one of claims 1-13, wherein said antibody comprises an Fc fragment.
The isolated antibody specifically recognizing MASP2 according to claim 14, wherein said antibody is a full-length IgG antibody.
The isolated antibody specifically recognizing MASP2 according to claim 15, wherein said antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.
The isolated antibody specifically recognizing MASP2 according to any one of claims 1-16, wherein said antibody is a chimeric, humanized or fully human antibody.
The isolated antibody specifically recognizing MASP2 according to any one of claims 1-17 is an antigen-binding fragment, wherein said antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab)' 2 , Fab'-SH, mono Chain antibody (scFv), Fv fragment, dAb, Fd, nanobody, diabody and linear antibody.
A nucleic acid molecule encoding the antibody specifically recognizing MASP2 according to any one of claims 1-18.
A vector comprising the nucleic acid molecule of claim 19.
An isolated host cell comprising the antibody specifically recognizing MASP2 according to any one of claims 1-18, the nucleic acid molecule according to claim 19 or the vector according to claim 20.
A method for preparing an antibody specifically recognizing MASP2, comprising:

a) cultivating the host cell described in claim 21 under conditions effective for expressing an antibody specifically recognizing MASP2; and

b) Obtaining the expressed antibody specifically recognizing MASP2 from the host cell.
A pharmaceutical composition, which comprises the antibody specifically recognizing MASP2 described in any one of claims 1-18, the nucleic acid molecule described in claim 19, the carrier described in claim 20, the carrier described in claim 21 The isolated host cell or the antibody prepared by the method of claim 22, and a pharmaceutically acceptable carrier.
The antibody of any one of claims 1-18, the nucleic acid molecule of claim 19, the vector of claim 20, the isolated host cell of claim 21, the nucleic acid molecule of claim 22 Use of the antibody prepared by the method, or the pharmaceutical composition described in claim 23, in the preparation of a medicament for treating, preventing or improving individual diseases or conditions in need.
A method for treating or preventing a disease or a disease, the method comprising administering an effective amount of the antibody according to any one of claims 1-18, the nucleic acid molecule described in claim 19, the nucleic acid molecule of claim 19, The vector of claim 20, the isolated host cell of claim 21, the antibody prepared by the method of claim 22, or the pharmaceutical composition of claim 23.
According to the use in claim 24 or the method in claim 25, wherein said disease or disease is autoimmune disease, inflammatory disease, blood disease, coagulation disease, angiogenesis dependence associated with MASP2-dependent complement activation Disease and/or viral infectious disease.
The use or method according to claim 26, wherein said disease or condition is selected from the group consisting of ischemia-reperfusion injury, atherosclerosis, mesangial proliferative glomerulonephritis, membranous glomerulonephritis, membranous hyperplasia Acute glomerulonephritis, acute postinfectious glomerulonephritis, cryoglobulinemia glomerulonephritis, lupus nephritis, Henoch-Schoenlein purpura nephritis, IgA nephropathy, severe sepsis, septic shock , acute respiratory distress syndrome or systemic inflammatory response syndrome caused by sepsis, hemorrhagic shock, hemolytic anemia, autoimmune thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), SARS type hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), TMA secondary to transplantation (TA-TMA), Upshaw-Schulman syndrome, catastrophic antiphospholipid syndrome (CAPS), German Goss disease (Degos disease), disseminated intravascular coagulation (DIC), angiogenesis-dependent cancer, age-related macular degeneration, proliferative diabetic retinopathy, vitreous hemorrhage secondary to proliferative diabetic retinopathy, neovascular glaucoma , corneal neovascularization, retinopathy of prematurity, and respiratory distress syndrome or pneumonia caused by coronavirus infection.
The use or method according to claim 27, wherein the coronavirus is SARS-CoV, MERS-CoV and/or SARS-CoV-2.
Use or method according to any one of claims 26-28, wherein the medicament is administered in combination with another medicament.
The use or method according to claim 29, wherein said another agent is selected from the group consisting of immunosuppressants, anti-inflammatory drugs, pain relievers, other complement inhibitors or vascular inhibitors.