Antibody specifically recognizing factor xiia and use thereof

Abstract

An antibody or an antigen-binding fragment thereof specifically recognizing factor XIIa, and a preparation method therefor and the use thereof.

Description

Antibodies specifically recognizing factor XIIa and their applications

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to patent application number PCT / CN2023 / 100653, application date 2023.06.16, and invention name “Antibodies specifically recognizing Factor XIIa and their applications”, and the entire contents of that application are incorporated herein by reference.

[0003] Submit sequence listing as XML file

[0004] The contents of the electronic sequence listing are incorporated herein by reference in their entirety: (FXIIa-WIPO seq.xml; size: 149 KB; and creation date: 2023.06.14). Technical Field

[0005] The present invention relates to antibodies that specifically recognize FXIIa, as well as preparation methods and uses thereof, including using the antibodies to treat thrombosis, diseases related to FXII / FXIIa-induced kinin formation, diseases related to FXII / FXIIa-induced complement activation, diseases related to the contact activation system, and inflammation-related diseases. Background Art

[0006] Factor XII (FXII) is an 80 kDa glycoprotein with a plasma concentration of approximately 40 μg / mL (approximately 500 nmol / L). FXII in plasma is primarily synthesized in the liver. FXII plays a role in activating the intrinsic pathway of coagulation and the kallikrein-kinin system. FXII undergoes autoactivation upon exposure to negatively charged surfaces (such as polyanionic surfaces, glass, polyphosphate, and ellagic acid), producing the active form, FXIIa. Activated FXIIa cleaves plasma prekallikrein (PK) to produce active plasma kallikrein (pKal). Activated pKal then cleaves FXII to FXIIa. The resulting FXIIa activates more PK, generating more pKal, thus creating a positive feedback loop and amplifying the effect.

[0007] Activated FXIIa consists of a heavy chain and a light chain, linked by a disulfide bond. The heavy chain contains the following domains: a fibronectin type II domain, an epidermal growth factor (EGF)-like domain I, a fibronectin type I domain, an EGF-like domain II, a kringle domain, and a proline-rich domain, which is unique to FXII. The heavy chain contains a region that binds to negatively charged surfaces, while the light chain contains the catalytic domain typical of serine proteases, resulting in a domain structure similar to other members of the serine protease family. The active site on the FXII light chain is composed of the typical catalytic triad of residues: His40, Asp89, and Ser191. This site is also the target of C1 esterase inhibitor (C1-INH), a major intrinsic inhibitor of the coagulation pathway. Cleavage by kallikrein or autoactivation results in cleavage of the Arg353-Val354 bound to the FXII zymogen, forming α-FXIIa (α-FXIIa), which contains the heavy and light chains linked by a disulfide bond. Two additional peptide bonds in the α-FXIIa form, upon cleavage by, for example, trypsin, yield the 30 kD β-FXIIa, which contains an intact light chain and a truncated heavy chain fragment. α-FXIIa is able to bind to negatively charged surfaces and activate FXI and PK. β-FXIIa lacks surface binding but can activate PK.

[0008] FXII deficiency, known as the Hageman trait, was first identified by Oscar Ratnoff as a defect that results in prolonged surface-activated blood coagulation tests such as the partial thromboplastin time (PTT) (Ratnoff et al., 1955, J Clin Invest, 34:602-13). Earl Davie was the first to purify Hageman factor and, according to convention, named it Factor XII. He and Ratnoff first demonstrated that FXII activates the plasma thrombin precursor FXI, and later demonstrated that FXIa activates FIX (Ratnoff et al., 1961, J Clin Invest, 40:803-19; Ratnoff et al., 1962, Biochemistry, 1:677-85). These results were the basis for their coagulation cascade hypothesis, proposed simultaneously with RG MacFarland, and also the basis for the contact activation hypothesis that initiates blood coagulation. It is known that the deficiency of coagulation factor XII is not associated with increased spontaneous or injury-related bleeding complications, but rather that the deficiency of FXII is associated with an increased risk of venous thrombosis (Kuhli C et al., 2004, Am J Ophthalmol, 137: 459-464; Halbmayer WM et al., 1993, Wien Med Wochenschr. 143: 43-50). Subsequent studies have also shown that FXII-deficient mice do not experience spontaneous or excessive injury-related bleeding, but are protected against collagen- and adrenaline-induced thromboembolism, and that infusion of human FXII into FXII-deficient mice can restore injury-induced thrombosis (Renne T et al., 2005, J Exp Med; 202(2): 271–281). These results suggest that FXII plays an important role in the pathological thrombosis process, and therefore interfering with or blocking FXII activity may be suitable for blocking pathogenic arterial thrombosis and its clinical consequences.

[0009] FXII not only plays a role in the intrinsic coagulation pathway, but also pKal, formed through FXIIa activation or other means, can activate the kallikrein-kinin system. pKal cleaves high molecular weight kininogen (HK) to release bradykinin (bradykinin) and kininogen fragments (i.e., cHK). Bradykinin affects vascular permeability by binding to the G protein-coupled receptor bradykinin B2 and B1 receptors. C1-INH, as the main inhibitor of FXIIa and pKal, regulates the contact activation system. Insufficient plasma levels or abnormal function of C1-INH cause continuous activation of FXIIa and pKal, leading to increased bradykinin formation (Caccia et al., 2014, Pediatr Allergy Immunol Pulmonol.; 27(4):159–163). The hereditary angioedema (HAE) syndromes are a group of diseases caused by a deficiency or defect in C1-INH (most commonly types I and II), or by increased function of FXIIa (type III), plasmin, or angiopoietin 1 (Bafunno V et al., 2018, J Allergy Clin Immunol;141:1009–17.). In type I HAE with C1-INH deficiency, neither FXIIa nor pKal is adequately inhibited, leading to enhanced bradykinin production and increased vascular permeability. To date, all of these different mechanisms, except the gain-of-function angiopoietin 1 mechanism, result in increased local bradykinin delivery to tissues, which causes vasodilation, increased vascular permeability, and angioedema (Caccia et al., 2014, Pediatr Allergy Immunol Pulmonol.;27(4):159–163). Blocking the bradykinin B2 receptor alleviates symptoms in many patients with HAE. Importantly, inhibition of the active enzyme of the contact-activated system by injection of C1-INH replacement products or inhibition of pKal by monoclonal antibodies or non-peptide mimetics can also improve and prevent type I and type II HAE in most patients (Banerji et al., 2018, JAMA, 320:2108–21; -Pürsün E et al., 2018, N Engl J Med; 379:352–62.).

[0010] Patent application WO2013014092A1 discloses an anti-FXII / FXIIa monoclonal antibody or antigen-binding fragment thereof. The antibody has a binding affinity for human FXIIa-β that is more than twice that for human FXII and is capable of inhibiting the amidolytic activity of human FXIIa. Patent application WO2017015431A1 discloses an anti-FXIIa antibody and methods of using the anti-FXII antibody to treat FXII-related diseases.

[0011] There remains a need in the art for therapeutic antibodies that effectively inhibit or otherwise antagonize FXII, as well as related methods for treating diseases or conditions mediated by FXII, such as thrombosis, diseases associated with FXII / FXIIa-induced kinin formation, diseases associated with FXII / FXIIa-induced complement activation, and diseases associated with the contact activation system.

[0012] The disclosures of all publications, patents, patent applications, and published patent applications mentioned herein are incorporated by reference in their entirety.

[0013] Application Overview

[0014] In some embodiments, an isolated anti-FXIIa antibody is provided, comprising a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising SQTMS (SEQ ID NO: 1); a HC-CDR2 comprising SX1X2X3ISX4RX5YYADSVKG (SEQ ID NO: 89), wherein X1 is I or S, X2 is H or S, X3 is H, V or Y, X4 is G, K or R, and X5 is A, D, K, M, N, P, R, S, T or Y; and a HC-CDR3 comprising X1HX2FDX3 (SEQ ID NO: 90), wherein X1 is A, G, H, Q, S or W, X2 is A, D or R, and X3 is L or V; and a light chain variable domain (V L ), the V L It comprises: a light chain complementary determining region (LC-CDR) 1 comprising RASQSX1X2X3X4LA (SEQ ID NO:91), wherein X1 is L or V, X2 is F, W or Y, X3 is S or Y, and X4 is A, H or N; a LC-CDR2 comprising GASTRAT (SEQ ID NO:65); and a LC-CDR3 comprising QQX1X2X3WPLS (SEQ ID NO:92), wherein X1 is N or Y, X2 is H, K, N or Q, and X3 is K, R or W.

[0015] In some embodiments, an isolated anti-FXIIa antibody is provided, comprising: (i) V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74; (ii) V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (iii) V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76; (iv) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (v) V H , the 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: 14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 54, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (vi) V H , the 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: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (vii) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (viii) V H , the 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: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (ix) V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (x) V H , the 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: 17, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xi) V H , the 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: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xii) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xiii) V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77; (xiv) V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xv) V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76; (xvi) V H , the 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: 18, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xvii) V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xviii) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xix) V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xx) V H , the 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: 20, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxi) V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxii) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxiii) V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxiv) V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 41; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxv) V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the VL comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 56, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78; (xxvi) V H , the 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: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxvii) V H , the 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: 22, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxviii) V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 42; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76; (xxix) V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and V L, the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxx) V H , the 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: 23, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxxi) V H , the 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: 24, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxxii) V H , the 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: 25, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75; (xxxiii) V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and VL , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79; (xxxiv) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80; (xxxv) V H , the 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: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0016] In some embodiments, an isolated anti-FXIIa antibody is provided comprising: (i) V H , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and V L , comprising the amino acid sequence of SEQ ID NO: 139 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 139; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 94; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (iii) VH , comprising the amino acid sequence of SEQ ID NO: 95 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 95; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (iv) V H , comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (v) V H , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 97; and V L , comprising the amino acid sequence of SEQ ID NO: 143 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 143; (vi) V H , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 98; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (vii) V H , comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 96; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (viii) V H , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 99; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (ix) V H, comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 94; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (x) V H , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xi) V H , comprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 101; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xii) V H , comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 102; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xiii) V H , comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 103; and V L , comprising the amino acid sequence of SEQ ID NO: 144 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 144; (xiv) V H , comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 104; and V L , comprising the amino acid sequence of SEQ ID NO: 145 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 145; (xv) V H, comprising the amino acid sequence of SEQ ID NO: 105 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 105; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (xvi) V H , comprising the amino acid sequence of SEQ ID NO: 106 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 106; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xvii) V H , comprising the amino acid sequence of SEQ ID NO: 107 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 107; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xviii) V H , comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xix) V H , comprising the amino acid sequence of SEQ ID NO: 109 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 109; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xx) V H , comprising the amino acid sequence of SEQ ID NO: 110 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 110; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxi) V H, comprising the amino acid sequence of SEQ ID NO: 111 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 111; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxii) V H , comprising the amino acid sequence of SEQ ID NO: 112 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 112; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (xxiii) V H , comprising the amino acid sequence of SEQ ID NO: 113 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 113; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxiv) V H , comprising the amino acid sequence of SEQ ID NO: 114 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 114; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxv) V H , comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 108; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxvi) V H , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 93; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxvii) V H, comprising the amino acid sequence of SEQ ID NO: 115 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 115; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxviii) V H , comprising the amino acid sequence of SEQ ID NO: 116 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 116; and V L , comprising the amino acid sequence of SEQ ID NO: 146 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 146; (xxix) V H , comprising the amino acid sequence of SEQ ID NO: 117 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 117; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxx) V H , comprising the amino acid sequence of SEQ ID NO: 118 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 118; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxi) V H , comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 104; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxxii) V H , comprising the amino acid sequence of SEQ ID NO: 119 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 119; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxiii) V H, comprising the amino acid sequence of SEQ ID NO: 120 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 120; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxiv) V H , comprising the amino acid sequence of SEQ ID NO: 111 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 111; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 142; (xxxv) V H , comprising the amino acid sequence of SEQ ID NO: 121 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 121; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxvi) V H , comprising the amino acid sequence of SEQ ID NO: 122 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 122; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (xxxvii) V H , comprising the amino acid sequence of SEQ ID NO: 123 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 123; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxxviii) V H , comprising the amino acid sequence of SEQ ID NO: 124 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 124; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxix) V H, comprising the amino acid sequence of SEQ ID NO: 125 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 125; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xl) V H , comprising the amino acid sequence of SEQ ID NO: 126 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 126; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xli) V H , comprising the amino acid sequence of SEQ ID NO: 112 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 112; and V L , comprising the amino acid sequence of SEQ ID NO: 147 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 147; (xlii) V H , comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, said variant having at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108; and V L , comprising the amino acid sequence of SEQ ID NO: 148 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 148; (xliii) V H , comprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 127; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xliv) V H , comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xlv) V H, comprising the amino acid sequence of SEQ ID NO: 129 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 129; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xlvi) V H , comprising the amino acid sequence of SEQ ID NO: 130 or a variant thereof, said variant having at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 130; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140.

[0017] In some embodiments, the isolated anti-FXIIa antibody binds to human FXIIa with a Kd value of 0.1 pM to 1 nM.

[0018] In some embodiments, any of the isolated anti-FXIIa antibodies described above comprises an Fc fragment. In some embodiments, the isolated anti-FXIIa antibody is a full-length IgG antibody. In some embodiments, the isolated anti-FXIIa antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the isolated anti-FXIIa antibody is a chimeric, fully human, or humanized antibody. In some embodiments, the isolated anti-FXIIa antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody, and linear antibody.

[0019] In some embodiments, an isolated nucleic acid molecule is provided, encoding any of the anti-FXIIa antibodies described above. In some embodiments, a vector is provided, comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, comprising any of the anti-FXIIa antibodies described above, any of the nucleic acid molecules described above, or any of the vectors described above. In some embodiments, a method for producing an anti-FXIIa antibody is provided, comprising: a) culturing any of the host cells described above under conditions effective to express the anti-FXIIa antibody; and b) obtaining the expressed anti-FXIIa antibody from the host cell.

[0020] In some embodiments, a method of treating a disease or condition in a desired individual is provided, comprising administering to the individual an effective amount of any of the anti-FXIIa antibodies described above. In some embodiments, use of any of the anti-FXIIa antibodies described above in the preparation of a pharmaceutical composition for treating a disease or condition in a desired individual is provided. In some embodiments, use of any of the anti-FXIIa antibodies described above or a pharmaceutical composition comprising an anti-FXIIa antibody in the preparation of a medicament for treating a disease or condition is provided. In some embodiments, the disease or condition is associated with the FXIIa signaling pathway, including thrombosis, diseases associated with FXII / FXIIa-induced kinin formation, diseases associated with FXII / FXIIa-induced complement activation, diseases associated with the contact activation system, and diseases or conditions associated with inflammation. In some embodiments, the disease or disorder is selected from, for example, venous, arterial or capillary thrombosis, intracardiac thrombosis, thrombosis during and / or after contacting the blood of a human or animal subject with an artificial surface, thromboembolism, atherosclerosis, interstitial lung disease, inflammation, neuroinflammatory disease, neurotraumatic disease, traumatic brain injury, complement activation, fibrinolysis, angiogenesis, hereditary angioedema (HAE), bacterial pulmonary infection, Trypanosoma infection, hypotensive shock, pancreatitis, Chagas disease, arthritis, arthritis, disseminated intravascular coagulation and sepsis, macular edema, diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, retinal vein occlusion, organ ischemia, remote ischemia-reperfusion injury (IRI), chronic kidney disease, renal fibrosis, multiple sclerosis.

[0021] Also provided are pharmaceutical compositions, kits, and articles of manufacture comprising any of the anti-FXIIa antibodies described above. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 shows the results of the inhibitory effects of exemplary anti-FXIIa antibodies FX-Y17-Y4, FX-Y17-Y8, FX-Y17-Y11, FX-Y17-Y23, FX-Y17-Y30, FX-Y17-Y34, and FX-Y17-Y45 on FXIIa-induced coagulation as detected by APTT.

[0023] FIG2 shows the results of the inhibition of FXIIa cleavage of PK proenzyme by exemplary anti-FXIIa antibodies FX-Y17-Y4, FX-Y17-Y34, and FX-Y17-Y45 using the pKa chemical substrate CS-3102.

[0024] FIG3 shows the results of a pharmacokinetic study of exemplary anti-FXIIa antibodies FX-Y17-Y4 and FX-Y17-Y4 (long-acting) in rats.

[0025] Figure 4A shows the effect of the exemplary anti-FXIIa antibody FX-Y17-Y4 on dye leakage in mouse intestinal tissue. Figure 4B shows the effect of the exemplary anti-FXIIa antibody FX-Y17-Y4 on dye retention in mouse blood.

[0026] Detailed description of this application

[0027] The present application provides, on the one hand, anti-FXIIa antibody molecules. Through a combination of natural scFv yeast library screening, affinity maturation, and appropriately designed biochemical and biological experiments, a highly effective antibody molecule has been identified that binds to human FXIIa and inhibits the interaction of human FXIIa with its receptor. The results presented herein demonstrate that the antibodies in the present application bind to different regions or epitopes of FXIIa compared to the known anti-FXIIa antibody CSL312 (CSL), and surprisingly, in various biological experiments, the antibodies in the present application have been shown to be even more effective than CSL312.

[0028] The anti-FXIIa antibodies provided herein include, for example, full-length anti-FXIIa antibodies, anti-FXIIa single-chain antibodies (scFvs), anti-FXIIa Fc fusion proteins, multispecific (eg, bispecific) anti-FXIIa antibodies, anti-FXIIa immunoconjugates, and the like.

[0029] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising SQTMS (SEQ ID NO: 1); a HC-CDR2 comprising SX1X2X3ISX4RX5YYADSVKG (SEQ ID NO: 89), wherein X1 is I or S, X2 is H or S, X3 is H, V or Y, X4 is G, K or R, and X5 is A, D, K, M, N, P, R, S, T or Y; and a HC-CDR3 comprising X1HX2FDX3 (SEQ ID NO: 90), wherein X1 is A, G, H, Q, S or W, X2 is A, D or R, and X3 is L or V; and a light chain variable domain (V L ), the V LIt comprises: a light chain complementary determining region (LC-CDR) 1 comprising RASQSX1X2X3X4LA (SEQ ID NO:91), wherein X1 is L or V, X2 is F, W or Y, X3 is S or Y, and X4 is A, H or N; a LC-CDR2 comprising GASTRAT (SEQ ID NO:65); and a LC-CDR3 comprising QQX1X2X3WPLS (SEQ ID NO:92), wherein X1 is N or Y, X2 is H, K, N or Q, and X3 is K, R or W.

[0030] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises GYHIH (SEQ ID NO: 2); HC-CDR2 comprises WIRVNGGNTMYARKFQG (SEQ ID NO: 26); and HC-CDR3 comprises RPYCSGGTCSDS (SEQ ID NO: 43); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RASESVFSNLA (SEQ ID NO: 57); a LC-CDR2 comprising DGNKRAT (SEQ ID NO: 66); and a LC-CDR3 comprising HQYNNWPPET (SEQ ID NO: 81).

[0031] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises DYSMN (SEQ ID NO: 3); HC-CDR2 comprises YISNSRSRSSKYYADSVKG (SEQ ID NO: 27); and HC-CDR3 comprises IGYCKNGVCGGAYDY (SEQ ID NO: 44); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RASQAIRNNLA (SEQ ID NO: 58); a LC-CDR2 comprising TASSLES (SEQ ID NO: 67); and a LC-CDR3 comprising LQYHDSPWT (SEQ ID NO: 82).

[0032] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H The antibody comprises a heavy chain complementarity determining region (HC-CDR) 1 comprising SSSYYWV (SEQ ID NO: 4); a HC-CDR2 comprising SIYHSGSTYYNPSLKS (SEQ ID NO: 28); and a HC-CDR3 comprising AATSGWYLRYWYFDL (SEQ ID NO: 45); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RANQNINSYLN (SEQ ID NO: 59); a LC-CDR2 comprising AATRLQS (SEQ ID NO: 68); and a LC-CDR3 comprising QQSYSSLRT (SEQ ID NO: 83).

[0033] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising HYWMH (SEQ ID NO: 5); HC-CDR2 comprising GITSSGGSKYYADSVKG (SEQ ID NO: 29); and HC-CDR3 comprising RGPPTHDS (SEQ ID NO: 46); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising QASQDITKYLN (SEQ ID NO: 60); a LC-CDR2 comprising DASILET (SEQ ID NO: 69); and a LC-CDR3 comprising QHYNSYSWT (SEQ ID NO: 84).

[0034] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H comprising: a heavy chain complementarity determining region (HC-CDR) 1 comprising SNSADWN (SEQ ID NO: 6); HC-CDR2 comprising RTYYRSKWYNDYAVSVKS (SEQ ID NO: 30); and HC-CDR3 comprising GGPRPLDI (SEQ ID NO: 47); and a light chain variable domain (V L ), the V LIt comprises: a light chain complementarity determining region (LC-CDR) 1 comprising KSSQSVLYRSKRKPNLA (SEQ ID NO:61); a LC-CDR2 comprising WASTRES (SEQ ID NO:70); and a LC-CDR3 comprising QQYYSTPLT (SEQ ID NO:85).

[0035] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises SNWIG (SEQ ID NO: 7); HC-CDR2 comprises IIYPDDSDTRYSPSFQG (SEQ ID NO: 31); and HC-CDR3 comprises QGSSTYYRVGWFDP (SEQ ID NO: 48); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RASQSISSYLN (SEQ ID NO: 62); a LC-CDR2 comprising AASSLQS (SEQ ID NO: 71); and a LC-CDR3 comprising QQSYSTPQT (SEQ ID NO: 86).

[0036] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V H The heavy chain complementarity determining region (HC-CDR) 1 comprises TNYMT (SEQ ID NO: 8); HC-CDR2 comprises VIYSGGSTYYADSVKG (SEQ ID NO: 32); and HC-CDR3 comprises GRYYDGVDYGPKYGMDV (SEQ ID NO: 49); and a light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RASQSVRYNLA (SEQ ID NO: 63); a LC-CDR2 comprising GASIRAT (SEQ ID NO: 72); and a LC-CDR3 comprising QFYGSSPLT (SEQ ID NO: 87).

[0037] On the other hand, the present application provides an anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: a heavy chain variable domain (V H ), the V HThe heavy chain complementarity determining region (HC-CDR) 1 comprises SYWMH (SEQ ID NO: 9); HC-CDR2 comprises RINLDGSSTGYADSVRG (SEQ ID NO: 33); and HC-CDR3 comprises SSRGFDP (SEQ ID NO: 50); and the light chain variable domain (V L ), the V L It comprises: a light chain complementarity determining region (LC-CDR) 1 comprising RASQSISSSYLA (SEQ ID NO: 64); a LC-CDR2 comprising GASRRAT (SEQ ID NO: 73); and a LC-CDR3 comprising QLYGHSAYT (SEQ ID NO: 88).

[0038] Also provided are nucleic acids encoding anti-FXIIa antibodies, compositions comprising anti-FXIIa antibodies, and methods of making and using anti-FXIIa antibodies.

[0039] definition

[0040] As used herein, "treatment" or "treating" is a method of obtaining beneficial or desired results, including clinical results. For the purposes of this application, the beneficial or desired clinical results include, but are 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 (e.g., preventing or delaying the worsening of the disease), preventing or delaying the spread of the disease (e.g., metastasis), preventing or delaying the recurrence of the disease, delaying or slowing the progression of the disease, improving the disease state, alleviating the disease (partially or completely), reducing the dose of one or more other drugs required to treat the disease, delaying the progression of the disease, improving or enhancing the quality of life, inhibiting coagulation, and / or inhibiting thrombosis. At the same time, "treatment" also includes a reduction in the pathological consequences of the disease (e.g., vascular permeability for hereditary angioedema). The methods of the present application contemplate any one or more aspects of these treatments.

[0041] 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 typically include three hypervariable loops, known as complementarity determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2, and LC-CDR3, and 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 highly conserved than the CDR regions and form a scaffold that supports 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 their heavy chain constant regions. The five major classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, which are characterized by having heavy chains of type α, δ, ε, γ, and μ, 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).

[0042] As used herein, the term "antigen-binding fragment" includes antibody fragments, such as diabodies, Fab, Fab', F(ab')2, Fv fragments, disulfide-stabilized Fv fragments (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabodies (dsdiabodies), single-chain Fv (scFv), scFv dimers (divalent diabodies), multispecific antibodies composed of antibody fragments comprising one or more CDRs, single-domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies, or any other antibody fragment that can bind to an antigen but does not contain a complete antibody structure. Antigen-binding fragments can bind to the same antigen as a parent antibody or parent antibody fragment (such as a parent scFv). Antigen-binding fragments also include fusion proteins comprising the above-mentioned antibody fragments. In some embodiments, an antigen-binding fragment may include one or more CDRs from a specific human antibody that are transplanted to a framework region from one or more different human antibodies.

[0043] As used herein, the term "epitope" refers to a specific group of atoms or amino acids on an antigen to which an antibody or antibody portion binds. If two antibodies or antibody portions exhibit competitive binding to an antigen, they likely bind to the same epitope on the antigen.

[0044] As used herein, a first antibody "competes" for binding to a second antibody for a FXIIa target when the first antibody, at equimolar concentrations, inhibits binding of the second antibody to the FXIIa target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%), and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody "epitope binning" method based on cross-competition.

[0045] As used herein, the terms "specifically bind," "specifically recognize," or "specific for" refer to a measurable and reproducible interaction, e.g., binding of an antibody to a target that can confirm the presence of the target in a heterogeneous population of molecules, including biomolecules. For example, an antibody that specifically recognizes a target (which may be an epitope) means that the antibody binds to the target with greater affinity, avidity, more readily, and / or more persistently than it binds to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with an affinity that is at least 10 times greater than its binding affinity to other targets.

[0046] As used herein, an "isolated" anti-FXIIa antibody refers to an anti-FXIIa antibody that (1) is not related to a naturally occurring protein, (2) does not contain other proteins from the same source, (3) is expressed by cells of a different species, or (4) does not occur in nature.

[0047] As used herein, the term "isolated nucleic acid" refers to a nucleic acid of genomic, cDNA, or synthetic origin, or a combination thereof. Depending on its origin, the "isolated nucleic acid" is (1) unrelated to all or part of the polynucleotide sequence found in nature, (2) operably linked to a polynucleotide sequence with which it is not naturally associated, or (3) not found in nature as part of a longer sequence.

[0048] As used herein, the term "CDR" or "complementarity determining region" refers to 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., USDept. of Health and Human Services, "Sequences of proteins of immunological interest" (1991); Chothia et al., J. Mol. Biol. 196: 901-917 (1987); Al-Lazikani B. et al. 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 MPet These specific regions are described in, for example, Desmond et al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlap or subsets of amino acid residues when compared to one another. However, any definition used to designate a CDR of an antibody, grafted antibody, or variant thereof is included within the scope of the term as defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the various references cited above 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 incorporated herein by reference in their entirety for use in this application and in one or more claims that may be included in this article.

[0049] Table 1: CDR definitions 1 The amino acid residue numbers refer to the nomenclature of Kabat et al.2 The amino acid residue numbers refer to the nomenclature of Chothia et al. 3 The amino acid residue numbers refer to the nomenclature of MacCallum et al. 4 The amino acid residue numbers refer to the nomenclature of Lefranc et al. 5 The amino acid residue numbers refer to the nomenclature of Honegger and Plückthun.

[0050] The term "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody from a particular species or belonging to a particular antibody class or subclass, while the remainder of the chain(s) is identical or homologous to the corresponding sequence in an antibody from another species or belonging to another antibody class or subclass, as well as fragments of such antibodies, as long as they have the biological activity described in the present application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81: 6851-6855 (1984)).

[0051] "Fv" is the smallest antibody fragment that contains a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly non-covalently linked. Six hypervariable loops (3 loops each in the light chain and heavy chain) are derived from the folding of these two domains. The hypervariable loops provide the antibody with amino acid residues for binding to the antigen and confer specificity for binding to the antibody. However, even a single variable domain (or half of an Fv fragment, which only contains 3 CDRs specific for the antigen) has the ability to recognize and bind to the antigen, although its affinity is lower than that of the complete binding site.

[0052] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a Fv that contains V molecules linked into a single polypeptide chain. H and V L In some embodiments, the scFv polypeptide further comprises a V H and V L The linker polypeptide between the domains allows the scFv to form an ideal 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).

[0053] The term "diabody" is used in V H and V L A small antibody fragment is prepared by constructing scFv fragments (see above) using short linkers (e.g., 5-10 residues) between the domains. This allows the variable domains to pair between chains rather than within the chain, resulting in a bivalent fragment, that is, a fragment with two antigen-binding sites. Bispecific diabodies are heterodimers of two "crossover" scFv fragments, in which the V domains of the two antibodies are H and V L The domains 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).

[0054] The "humanized" form of a non-human (such as a rodent) antibody is a chimeric antibody that includes minimal sequences from a non-human antibody. In most cases, a humanized antibody is a human immunoglobulin (recipient antibody) in which the hypervariable region (HVR) residues of the recipient antibody are replaced by hypervariable region residues from a non-human species such as a mouse, rat, rabbit or non-human mammal with ideal antibody specificity, affinity and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced by corresponding non-human residues. In addition, a humanized antibody may include residues that are not present in either the recipient antibody or the donor antibody. These modifications can further improve the performance of the antibody. Typically, a humanized antibody will comprise substantially all, at least one, and usually two variable domains, wherein all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences. The human antibody optionally also comprises at least a portion of an immunoglobulin constant region (Fc), typically a constant region of a human immunoglobulin. For details, see 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).

[0055] The "percent (%) amino acid sequence identity" or "homology" of the polypeptide and antibody sequences identified herein is defined as the percentage of identical amino acid residues in a candidate sequence and the polypeptide sequence being compared, when the sequences are aligned, considering conservative substitutions as part of the sequence identity. Percent amino acid sequence identity can be determined by various alignment methods within the skill in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. One skilled in the art can determine appropriate parameters for measuring alignment, including any algorithm needed to maximize alignment over the full length of the sequences being compared. However, for the purposes of this article, percent amino acid sequence identity values ​​are generated using the sequence alignment computer program MUSCLE (Edgar, RC, Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, RC, BMC Bioinformatics 5(1):113, 2004).

[0056] The term "Fc receptor" or "FcR" is used to describe a receptor that binds to the Fc region of an antibody. In some embodiments, the FcR described herein is an FcR that binds to an IgG antibody (a gamma receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternatively spliced ​​forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("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-based activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine-based inhibition motif (ITIM) (see M.in Annu. Rev. Immunol. 15:203-234 (1997). The term also includes allotypes, such as the FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131, and / or FcγRIIA-H131. FcRs are described 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. 126:330-41 (1995). The term FcR in this application encompasses other types of FcRs, including those identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).

[0057] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC) and consists of an α chain non-covalently bound to β2 microglobulin. The various 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 immunoglobulins (IgGs) from mother to newborn and in regulating serum IgG levels. As a salvage receptor, FcRn can bind and transport endocytosed IgGs in their intact form within and between cells, protecting them from the default degradation pathway.

[0058] The "CH1 domain" of a human IgG heavy chain constant region typically stretches from amino acid 118 to amino acid 215 (EU numbering system).

[0059] The "hinge region" is generally defined as stretching from Glu 216 to Pro 230 of human IgG1 (Burton, Molec. Immunol. 22: 161-206 (1985)). By placing the first and last cysteine ​​residues that form inter-heavy chain disulfide bonds in the same positions as in IgG1, the hinge regions of other IgG isotypes can be aligned with the IgG1 sequence.

[0060] The "CH2 domain" of the human IgG Fc region typically extends from amino acids 231 to 340. The CH2 domain is unique in that it does not closely pair with another domain. Instead, two N-terminally linked branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is hypothesized that carbohydrates may serve as a substitute for domain-to-domain pairing, helping to maintain CH2 domain stability. Burton, Molec. Immunol. 22:161-206 (1985).

[0061] The "CH3" domain includes the CH2 domain extending from the C-terminal residue within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, usually amino acid residue 446 or 447 in IgG).

[0062] A "functional Fc fragment" possesses the "effector functions" of a native Fc region sequence. Exemplary "effector functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (e.g., B cell receptor; BCR). Such effector functions generally require the Fc region to be bound to a binding domain (e.g., an antibody variable region) and can be assessed using a variety of experimental methods known in the art.

[0063] IgG Fc variant antibodies with "altered" FcR binding affinity or ADCC activity have increased or decreased FcR binding activity and / or ADCC activity compared to the parent polypeptide or a polypeptide comprising a native Fc sequence. Fc variants that exhibit "enhanced binding" to FcRs have a higher binding affinity (e.g., lower apparent Kd or IC) to at least one FcR compared to the parent polypeptide or a polypeptide comprising a native IgG Fc sequence. 50 In some embodiments, the binding capacity is enhanced by 3-fold, e.g., 5-, 10-, 25-, 50-, 60-, 100-, 150-, 200-, or even up to 500-fold, or the binding capacity is increased by 25% to 1000%, compared to the parent polypeptide. An Fc variant that exhibits "reduced binding" to an FcR has a lower affinity for at least one FcR (e.g., a higher apparent Kd or IC) than the parent polypeptide. 50 Compared with the parent polypeptide, its binding capacity is reduced by 40% or more.

[0064] "Antibody-dependent cell-mediated cytotoxicity" or "ADCC" is a form of cytotoxicity that refers to the binding of secreted Ig to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages), enabling these cytotoxic effector cells to specifically bind to target cells bearing antigen and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are required for this killing. Of the major cell types that mediate ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. The expression of FcRs 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 target molecule, an in vitro ADCC assay can be performed, as described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK). Alternatively, or in addition, the ADCC activity of the target molecule can also be assessed in vivo, for example, as described in the animal model disclosed in Clynes et al. PNAS (USA) 95: 652-656 (1998).

[0065] Polypeptides comprising Fc region variants exhibit "enhanced ADCC activity" or are capable of more effectively mediating ADCC in the presence of human effector cells, compared to polypeptides comprising wild-type IgG Fc polypeptides or parent polypeptides. When tested in substantially the same quantity as polypeptides comprising wild-type IgG Fc polypeptides (or parent polypeptides), such polypeptides comprising Fc region variants are capable of more effectively mediating ADCC, both in vitro and in vivo. Such variants are generally identified using any in vitro ADCC assay known in the art, such as assays or methods for identifying ADCC activity, such as in animal models. In some embodiments, such variants mediate ADCC 5- to 100-fold more efficiently, such as 25- to 50-fold more efficiently, than wild-type Fc (or parent polypeptide).

[0066] "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 (C1q) to an antibody (of the appropriate structural subclass) that binds to the cognate antigen. To assess complement activation, a CDC assay, such as that described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996), can be performed. Polypeptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding capacity are described in U.S. Patent No. 6,194,551 B1 and WO 99 / 51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).

[0067] Unless otherwise indicated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and encode the same amino acid sequence. A nucleotide sequence encoding a protein or RNA may also include introns, for example, a nucleotide sequence encoding a protein may contain introns in some forms.

[0068] The term "operably linked" refers to a functional connection between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling expression of the latter. 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. Generally, operably linked DNA sequences are contiguous and, if necessary, can link two protein coding regions in the same reading frame.

[0069] "Homologous" refers to the sequence similarity or sequence identity between two polypeptides or between two nucleic acid molecules. If the same base or amino acid monomer subunit is present at the same position in two compared sequences, for example, adenine is present at the same position in two DNA molecules, then the two DNA molecules are homologous at that position. The percentage homology between two sequences refers to 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 between the two sequences is 60%. For example, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally speaking, when aligning two sequences, the comparison is performed with the goal of obtaining maximum homology.

[0070] An "effective amount" of an anti-FXIIa antibody or composition disclosed herein is an amount sufficient to achieve a specific purpose. An "effective amount" can be determined empirically and by known methods relevant to the stated purpose.

[0071] The term "therapeutically effective amount" refers to an amount of an anti-FXIIa antibody or composition disclosed herein that is effective in treating a disease or condition in a subject. For example, in the case of thrombosis, a therapeutically effective amount of an anti-FXIIa antibody or composition thereof is one that inhibits (i.e., slows to some extent) FXII / FXIIa enzyme activity; prolongs (i.e., prolongs to some extent) the activated partial thromboplastin time (aPTT); reduces (i.e., eliminates to some extent) the size and / or volume of thrombi; reduces (i.e., eliminates to some extent) fibrin deposition; reduces (i.e., eliminates to some extent) platelet deposition; reduces vascular occlusion rate; increases vascular permeability; inhibits (i.e., slows to some extent or preferably stops) the overactivation of kallikrein; and alleviates to some extent one or more symptoms associated with thrombosis. The anti-FXIIa antibodies or compositions disclosed herein are capable of inhibiting and / or killing existing tumor cells, which can be cytostatic or cytotoxic. In some embodiments, a therapeutically effective amount is an amount that can prolong a patient's survival. In some embodiments, a therapeutically effective amount is an amount that can improve a patient's progression-free survival.

[0072] As used herein, "pharmaceutically acceptable" or "pharmacologically compatible" refers to a material that is free of biological activity or other undesirable properties, e.g., a material that can be added to a pharmaceutical composition administered to a patient without causing a significant adverse biological reaction, or that does not interact in a deleterious manner with any other component contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicology or manufacturing testing and / or are included in the inactive ingredient guide compiled by the U.S. Food and Drug Administration.

[0073]

[0066] The embodiments of the present application described herein should be understood to include "consisting of" and / or "consisting essentially of" embodiments.

[0074] Reference herein to "about" for a value or parameter includes (and describes) variations of the value or parameter itself. For example, a description involving "about X" includes a description of "X".

[0075] As used herein, reference to "not" a value or parameter generally indicates and describes "other than" a value or parameter. For example, "the method cannot be used to treat type X cancer" means that the method is generally used to treat other types of cancer besides type X cancer.

[0076] As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0077] Anti-FXIIa antibodies

[0078] On the one hand, the application provides anti-human or / and rhesus monkey FXIIa antibodies that specifically bind to FXIIa. The anti-FXIIa antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and / or light chain CDRs as described herein. On the one hand, the application provides antibodies separated from FXIIa. Expected anti-FXIIa antibodies include, for example, full-length anti-FXIIa antibodies (such as full-length IgG1 or IgG4), anti-FXIIa single-chain antibodies, anti-FXIIa Fc fusion proteins, multispecific (such as bispecific) anti-FXIIa antibodies, anti-FXIIa immunoconjugates, and the like. In certain embodiments, the anti-FXIIa antibody is a full-length antibody (such as full-length IgG1 or IgG4) or an antigen-binding fragment thereof that specifically binds to FXIIa. In some embodiments, the anti-FXIIa antibody is a Fab, Fab', F(ab)'2, Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody or linear antibody. In some embodiments, an antibody that specifically binds to FXIIa means that the antibody binds to FXIIa with an affinity that is at least 10 times greater than the affinity for binding to a non-target (e.g., 10 ... 2 , 10 3 , 10 4 , 10 5 , 10 6 , or 10 7 times). In some embodiments, non-target refers to an antigen that is not FXIIa. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence-activated cell sorting (FACS) analysis, or radioimmunoprecipitation assay (RIA). Kd values ​​can be determined by methods known in the art, such as surface plasmon resonance (SPR) or biolayer interferometry (BLI).

[0079] Although anti-FXIIa antibodies comprising human sequences (e.g., human heavy and light chain variable domains comprising human CDR sequences) are generally discussed herein, non-human anti-FXIIa antibodies are also contemplated. In some embodiments, non-human anti-FXIIa antibodies comprise human CDR sequences of anti-FXIIa antibodies described herein and non-human framework sequences. In some embodiments, non-human framework sequences include any sequence used to generate heavy and / or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals such as mice, rats, rabbits, pigs, cattle (e.g., cows, bulls, buffaloes), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., small apes, macaques), etc. In some embodiments, non-human anti-FXIIa antibodies include anti-FXIIa antibodies generated by grafting one or more human CDR sequences described herein into non-human framework sequences (e.g., mouse or chicken framework sequences).

[0080] The complete amino acid sequence of an exemplary human FXII comprises or consists of the amino acid sequence set forth in SEQ ID NO:161.

[0081] In some embodiments, the anti-FXIIa antibodies described herein specifically recognize an epitope in human FXIIa. In some embodiments, the anti-FXIIa antibodies cross-react with FXIIa from species other than human. In some embodiments, the anti-FXIIa antibodies are completely specific for human FXIIa and do not cross-react with other non-human species.

[0082] In some embodiments, the anti-FXIIa antibody cross-reacts with at least one allelic variant of the FXIIa protein (or a fragment thereof). In some embodiments, the allelic variant has up to 30 (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) amino acid substitutions (e.g., conservative substitutions) compared to a naturally occurring FXIIa protein (or a fragment thereof). In some embodiments, the anti-FXIIa antibody does not cross-react with any allelic variant of the FXIIa protein (or a fragment thereof).

[0083] In some embodiments, the anti-FXIIa antibody cross-reacts with at least one interspecies variant of the FXIIa protein. In some embodiments, for example, the FXIIa protein (or fragment thereof) is human FXIIa, and the interspecies variant of the FXIIa protein (or fragment thereof) is a variant in cynomolgus macaque. In some embodiments, the anti-FXIIa antibody does not cross-react with any interspecies variant of the FXIIa protein.

[0084] In some embodiments, as described herein, any anti-FXIIa antibody comprises an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-FXIIa antibody comprises an IgG1 heavy chain constant region. In some embodiments, the anti-FXIIa antibody comprises an IgG2 heavy chain constant region. In some embodiments, the anti-FXIIa antibody comprises an IgG3 heavy chain constant region. In some embodiments, the anti-FXIIa antibody comprises an IgG4 heavy chain constant region. In some embodiments, the heavy chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 158. In some embodiments, the anti-FXIIa antibody comprises a kappa light chain constant region. In some embodiments, the light chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 159. In some embodiments, the anti-FXIIa antibody comprises a lambda light chain constant region. In some embodiments, the light chain constant region comprises (consists of, or consists essentially of) the amino acid sequence of SEQ ID NO: 160. In some embodiments, the anti-FXIIa antibody comprises an antibody heavy chain variable domain and an antibody light chain variable domain.

[0085] In some embodiments, the anti-FXIIa antibody comprises a heavy chain variable domain (V H ), the V H The invention comprises: a heavy chain complementary determining region (HC-CDR) 1 comprising SQTMS (SEQ ID NO: 1); a HC-CDR2 comprising SX1X2X3ISX4RX5YYADSVKG (SEQ ID NO: 89), wherein X1 is I or S, X2 is H or S, X3 is H, V or Y, X4 is G, K or R, and X5 is A, D, K, M, N, P, R, S, T or Y; and a HC-CDR3 comprising X1HX2FDX3 (SEQ ID NO: 90), wherein X1 is A, G, H, Q, S or W, X2 is A, D or R, and X3 is L or V; and a light chain variable domain (V L ), the V LIt comprises: a light chain complementary determining region (LC-CDR) 1 comprising RASQSX1X2X3X4LA (SEQ ID NO:91), wherein X1 is L or V, X2 is F, W or Y, X3 is S or Y, and X4 is A, H or N; a LC-CDR2 comprising GASTRAT (SEQ ID NO:65); and a LC-CDR3 comprising QQX1X2X3WPLS (SEQ ID NO:92), wherein X1 is N or Y, X2 is H, K, N or Q, and X3 is K, R or W.

[0086] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence shown in SEQ ID NO: 1 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence shown in any one of SEQ ID NOs: 10-25 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence shown in any one of SEQ ID NOs: 34-42 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids.

[0087] In some embodiments, the anti-FXIIa antibody comprises V H , the V H It 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 any one of SEQ ID NOs: 10-25, and HC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs: 34-42.

[0088] In some embodiments, the anti-FXIIa antibody comprises V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-56 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:65 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:74-80 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0089] In some embodiments, the anti-FXIIa antibody comprises VL , the V L It comprises: LC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-56, LC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:65, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:74-80.

[0090] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-25 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 34-42 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and V L , the V L Comprising: LC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-56 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:65 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:74-80 or a variant thereof, wherein the variant comprises substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0091] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-25, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 34-42; and V L , the V LIt comprises: LC-CDR1, which comprises the amino acid sequence shown in any one of SEQ ID NOs:51-56, LC-CDR2, which comprises the amino acid sequence shown in any one of SEQ ID NOs:65, and LC-CDR3, which comprises the amino acid sequence shown in any one of SEQ ID NOs:74-80.

[0092] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0093] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:74.

[0094] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 11, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and VL , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0095] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0096] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 12, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0097] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:76.

[0098] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0099] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0100] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 54, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0101] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75.

[0102] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 15, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0103] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0104] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0105] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0106] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 16, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0107] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0108] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 11, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0109] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0110] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 17, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0111] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 17, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0112] In some embodiments, the anti-FXIIa antibody comprises VH , the 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: 16, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0113] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0114] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0115] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0116] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0117] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77.

[0118] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 11, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0119] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75.

[0120] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 12, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76, or the V LA variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0121] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:76.

[0122] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 18, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0123] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 18, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0124] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 19, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0125] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0126] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the VL A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0127] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0128] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 19, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 40, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0129] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0130] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 20, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0131] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 20, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0132] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 19, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V Lcomprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0133] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0134] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0135] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the VL It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0136] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0137] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0138] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 41, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L, the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0139] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 41; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0140] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 56, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0141] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and VL , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 56, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78.

[0142] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 21, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0143] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0144] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 22, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V HA variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0145] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 22, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0146] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 12, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 42, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0147] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 42; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:76.

[0148] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0149] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0150] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0151] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 23, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0152] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 24, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0153] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 24, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0154] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 25, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0155] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 25, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0156] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 12, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0157] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79.

[0158] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0159] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80.

[0160] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 21, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0161] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75.

[0162] In some embodiments, the anti-FXIIa antibody comprises VH , the V H Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 93-130 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , the V L Comprising V as shown in any one of the amino acid sequences of SEQ ID NOs: 139-148 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0163] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:93 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 139 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0164] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:94 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0165] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:95 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 141 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0166] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:96 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L, which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0167] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:97 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 143 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0168] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:98 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0169] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:96 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0170] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:99 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0171] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:94 HHC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0172] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 100 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0173] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 101 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0174] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 102 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0175] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 103 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 144 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0176] In some embodiments, the anti-FXIIa antibody comprises VH , which comprises V as shown in the amino acid sequence SEQ ID NO: 104 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 145 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0177] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 105 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 141 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0178] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 106 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0179] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 107 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0180] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 108 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0181] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 109 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0182] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 110 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0183] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:111 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0184] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 112 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 141 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0185] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 113 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L, which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0186] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 114 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0187] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 108 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0188] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:93 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0189] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 115 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0190] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 116H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 146 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0191] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 117 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0192] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 118 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0193] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 104 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0194] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 119 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0195] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 120 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0196] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO:111 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0197] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 121 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0198] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 122 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 141 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0199] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 123 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 142 LContains LC-CDR1, LC-CDR2 and LC-CDR3.

[0200] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 124 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0201] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 125 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0202] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 126 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0203] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 112 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 147 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0204] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 108 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and VL , which comprises V as shown in the amino acid sequence SEQ ID NO: 148 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0205] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 127 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0206] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 128 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0207] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 129 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0208] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 130 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 140 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0209] In some embodiments, the anti-FXIIa antibody comprises: V H , the V Hcomprising an amino acid sequence as set forth in any one of SEQ ID NOs: 93-130, or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence as set forth in any one of SEQ ID NOs: 93-130; and V L , the V L comprising the amino acid sequence of any one of SEQ ID NOs: 139-148 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of any one of SEQ ID NOs: 139-148. In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 93-130, and V L , the V L Comprising the amino acid sequence shown in any one of SEQ ID NOs: 139-148.

[0210] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 93; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 139 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 139. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 93, and V L , the V L Comprising the amino acid sequence SEQ ID NO:139.

[0211] In some embodiments, the anti-FXIIa antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 94, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0212] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 95 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 95; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 141. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 95, and V L , the V L Comprising the amino acid sequence SEQ ID NO:141.

[0213] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 96; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 96, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0214] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 97; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 143 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 143. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 97, and V L , the V L Comprising the amino acid sequence SEQ ID NO:143.

[0215] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 98; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H, the V H Comprising the amino acid sequence SEQ ID NO: 98, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0216] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 96; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 96, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0217] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 99; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 99, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0218] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 94; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 94, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0219] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 100; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 100, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0220] In some embodiments, the anti-FXIIa antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 101; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 101, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0221] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 102; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 102, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0222] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 103; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 144 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 144. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 103, and V L , the V L Comprising the amino acid sequence SEQ ID NO:144.

[0223] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 104; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 145 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 145. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 104, and V L , the V L Comprising the amino acid sequence SEQ ID NO:145.

[0224] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 105 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 105; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 141. In some embodiments, the anti-FXIIa antibody comprises V H, the V H Comprising the amino acid sequence SEQ ID NO: 105, and V L , the V L Comprising the amino acid sequence SEQ ID NO:141.

[0225] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 106 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 106; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 106, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0226] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 107 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 107; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 107, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0227] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 108; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 108, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0228] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 109 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 109; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 109, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0229] In some embodiments, the anti-FXIIa antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 110 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 110; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 110, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0230] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 111 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 111; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 111, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0231] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 112 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 112; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 141. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 112, and V L , the V L Comprising the amino acid sequence SEQ ID NO:141.

[0232] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 113 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 113; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 113, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0233] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 114 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 114; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H, the V H Comprising the amino acid sequence SEQ ID NO: 114, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0234] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 108; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 108, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0235] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 93; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 93, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0236] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 115 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 115; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 115, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0237] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 116 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 116; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 146 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 146. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 116, and V L , the V L Comprising the amino acid sequence SEQ ID NO:146.

[0238] In some embodiments, the anti-FXIIa antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 117 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 117; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 117, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0239] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 118 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 118; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 118, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0240] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 104; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 104, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0241] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 119 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 119; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 119, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0242] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 120 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 120; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H, the V H Comprising the amino acid sequence SEQ ID NO: 120, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0243] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 111 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 111; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 111, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0244] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 121 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 121; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 121, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0245] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 122 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 122; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 141. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 122, and V L , the V L Comprising the amino acid sequence SEQ ID NO:141.

[0246] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 123 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 123; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 142. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 123, and V L , the V L Comprising the amino acid sequence SEQ ID NO:142.

[0247] In some embodiments, the anti-FXIIa antibody comprises: V H , the V Hcomprising the amino acid sequence of SEQ ID NO: 124 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 124; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 124, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0248] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 125 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 125; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 125, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0249] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 126 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 126; and V L , the V Lcomprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 126, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0250] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 112 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 112; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 147 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 147. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 112, and V L , the V L Comprising the amino acid sequence SEQ ID NO:147.

[0251] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 108; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 148 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 148. In some embodiments, the anti-FXIIa antibody comprises V H, the V H Comprising the amino acid sequence SEQ ID NO: 108, and V L , the V L Comprising the amino acid sequence SEQ ID NO:148.

[0252] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 127; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 127, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0253] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 128; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 128, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0254] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 129 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 129; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 129, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0255] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 130 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 130; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 140. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 130, and V L , the V L Comprising the amino acid sequence SEQ ID NO:140.

[0256] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 43, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 57, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0257] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 26, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:57, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:66, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:81.

[0258] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 131 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 149 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0259] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 131 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 131; and V L , the VL comprising the amino acid sequence of SEQ ID NO: 149 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 149. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 131, and V L , the V L Comprising the amino acid sequence SEQ ID NO:149.

[0260] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 27, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 44, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 58, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 67, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0261] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 27, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 44; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:58, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:67, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:82.

[0262] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 132H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 150 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0263] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 132 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 132; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 150 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 150. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 132, and V L , the V L Comprising the amino acid sequence SEQ ID NO:150.

[0264] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 45, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 59, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 68, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0265] In some embodiments, the anti-FXIIa antibody comprises V H , the 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: 28, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 45; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:59, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:68, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:83.

[0266] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 133 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 151 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0267] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 133 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 133; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 151 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 151. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 133, and V L , the V L Comprising the amino acid sequence SEQ ID NO:151.

[0268] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 60, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 69, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0269] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:60, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:69, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:84.

[0270] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 134 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 152 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0271] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 134 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 134; and V L , the VL comprising the amino acid sequence of SEQ ID NO: 152 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 152. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 134, and V L , the V L Comprising the amino acid sequence SEQ ID NO:152.

[0272] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 47, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 70, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 85, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0273] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 47; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:61, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:70, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:85.

[0274] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 135H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 153 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0275] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 135 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 135; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 153 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 153. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 135, and V L , the V L Comprising the amino acid sequence SEQ ID NO:153.

[0276] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 31, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 48, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 62, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 71, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 86, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0277] In some embodiments, the anti-FXIIa antibody comprises V H , the VH comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 31, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 48; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:62, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:71, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:86.

[0278] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 136 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 154 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0279] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 136 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 136; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 154 or a variant thereof, wherein the variant has at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 154. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 136, and V L , the V L Comprising the amino acid sequence SEQ ID NO:154.

[0280] In some embodiments, the anti-FXIIa antibody comprises V H , the V Hcomprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 49, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 63, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 87, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0281] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 49; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:63, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:72, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:87.

[0282] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 137 H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 155 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0283] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 137 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 137; and V L , the VL comprising the amino acid sequence of SEQ ID NO: 155 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 155. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 137, and V L , the V L Comprising the amino acid sequence SEQ ID NO:155.

[0284] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 9, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 33, HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 50, or the V H A variant comprising up to about 5 amino acid substitutions in its HC-CDRs; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 64, LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 73, LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 88, or the V L A variant comprising up to about 5 amino acid substitutions in its LC-CDRs.

[0285] In some embodiments, the anti-FXIIa antibody comprises V H , the V H comprising: HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 9, HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 50; and V L , the V L It comprises: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:64, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:73, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:88.

[0286] In some embodiments, the anti-FXIIa antibody comprises V H , which comprises V as shown in the amino acid sequence SEQ ID NO: 138H HC-CDR1, HC-CDR2 and HC-CDR3 included; and V L , which comprises V as shown in the amino acid sequence SEQ ID NO: 156 L Contains LC-CDR1, LC-CDR2 and LC-CDR3.

[0287] In some embodiments, the anti-FXIIa antibody comprises: V H , the V H comprising the amino acid sequence of SEQ ID NO: 138 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 138; and V L , the V L comprising the amino acid sequence of SEQ ID NO: 156 or a variant thereof having at least about 80% (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity to the amino acid sequence of SEQ ID NO: 156. In some embodiments, the anti-FXIIa antibody comprises V H , the V H Comprising the amino acid sequence SEQ ID NO: 138, and V L , the V L Comprising the amino acid sequence SEQ ID NO:156.

[0288] In some embodiments, the above-mentioned amino acid substitutions are limited to the "exemplary substitutions" shown herein in Table 4. In some embodiments, the amino acid substitutions are limited to the "preferred substitutions" shown herein in Table 4.

[0289] In some embodiments, functional epitopes can be resolved using combinatorial alanine scanning. In this process, combinatorial alanine scanning can be used to identify amino acids in the FXIIa protein that are essential for interaction with an anti-FXIIa antibody. In some embodiments, the epitope is conformational and can be identified using a crystal structure of an anti-FXIIa antibody bound to the FXIIa protein.

[0290] In some embodiments, the present application provides antibodies that competitively bind to FXIIa with any of the anti-FXIIa antibodies described herein. In some embodiments, antibodies that can competitively bind to an epitope on FXIIa with any of the anti-FXIIa antibodies described herein are provided. In some embodiments, anti-FXIIa antibodies are provided that are combined with a V H and V L The anti-FXIIa antibody molecules bind to the same epitope, wherein the VH comprising the amino acid sequence shown in any one of SEQ ID NOs: 93-138, and said V L comprising the amino acid sequence shown in any one of SEQ ID NOs: 139-156. In some embodiments, an anti-FXIIa antibody is provided, which is combined with a V H and V L The anti-FXIIa antibody competitively binds to FXIIa, wherein the V H comprising the amino acid sequence shown in any one of SEQ ID NOs: 93-138, and said V L Comprising the amino acid sequence shown in any one of SEQ ID NOs: 139-156.

[0291] In some embodiments, competition assays can be used to identify monoclonal antibodies that compete with the anti-FXIIa antibodies described herein for binding to FXIIa. Competition assays can determine whether two antibodies bind to the same epitope by recognizing the same or spatially overlapping epitopes or by competitively inhibiting antigen binding of one antibody to the other. 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 described in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for resolving epitopes bound by antibodies are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, each antibody is said to bind to the same epitope if it blocks 50% or more of the binding of the other antibody. In some embodiments, the antibodies that compete with the anti-FXIIa antibodies described herein are chimeric, humanized, or fully human antibodies.

[0292] Exemplary anti-FXIIa antibody sequences are shown in Tables 2 and 3, where CDR numbering is performed according to the Kabat definition. Those skilled in the art will recognize that there are a variety of known algorithms for predicting the positions of CDRs and defining the variable regions of antibody light and heavy chains. H and / or V L Sequences, but based on prediction algorithms other than those exemplified in the table below, are also within the scope of this application.

[0293] Table 2 Exemplary anti-FXIIa antibody CDR sequences

[0294] Table 3 Exemplary sequences

[0295] FXIIa

[0296] There are two convergent pathways of coagulation, triggered by either extrinsic (vessel wall) or intrinsic (blood-borne) components of the vascular system. The extrinsic pathway is initiated by a complex of factor VII (FVII) and the intrinsic membrane protein tissue factor (TF). TF, expressed in circulating microvesicles, may also promote clot propagation by maintaining thrombin generation on the surface of activated platelets. The intrinsic, or contact-activated, pathway is initiated when FXII comes into contact with a negatively charged surface in a reaction. Robert Colman first described FXII and contact activation as a surface-activated defense mechanism to describe contact activation with foreign pathogens (e.g., bacteria, viruses, yeast, parasites) or artificial surfaces (e.g., glass, medical devices) (Colman RW et al., 1997, Blood;90:3819–43). FXII has the unique property of autoactivating from a zymogen to an active enzyme. When the zymogen is incubated alone with a negatively charged surface, FXII autoactivation is slow (90–120 minutes). When FXII is incubated with PK and HK or in plasma, the autoactivation process is greatly accelerated. FXIIa is a serine protease whose substrates include PK, FXI, plasminogen, complement component 1r (C1r), C1s, and HK. FXIIa activates PK to pKal, resulting in a mutually activated state where pKal activates FXII. The resulting FXIIa activates more PK, thereby amplifying the activity of the system. HK stabilizes PK for optimal activation of FXIIa. Autoactivation, reciprocal activation, and amplification are the essence of the contact activation system (CAS) (Tankersley DL et al., 1984, Biochemistry; 23:273–9). The formation of pKal by FXIIa activation or other means initiates the so-called kallikrein-kinin system. pKal cleaves HK, releasing bradykinin and a kininogen fragment (cHK). Bradykinin affects vascular permeability by binding to the G protein-coupled receptors bradykinin B2 and B1. FXIIa activates FXI to initiate contact activation of coagulation. FXIIa activates plasminogen, which in turn activates C1r / C1s to initiate fibrinolysis and classical complement activation, respectively.

[0297] Full-length anti-FXIIa antibody

[0298] In some embodiments, the anti-FXIIa antibody is a full-length anti-FXIIa antibody. In some embodiments, the full-length anti-FXIIa antibody is IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-FXIIa antibody comprises an IgG constant region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the full-length anti-FXIIa antibody comprises a lambda light chain constant region. In some embodiments, the full-length anti-FXIIa antibody comprises a kappa light chain constant region. In some embodiments, the full-length anti-FXIIa antibody is a full-length human anti-FXIIa antibody. In some embodiments, the full-length anti-FXIIa antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-FXIIa antibody comprises an altered or otherwise modified Fc sequence such that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) effector functions.

[0299] Thus, for example, in some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided that specifically binds to FXIIa. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0300] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG2 constant region is provided, wherein the anti-FXIIa antibody specifically binds to FXIIa. 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: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0301] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG3 constant region is provided, wherein the anti-FXIIa antibody specifically binds to FXIIa. In some embodiments, the IgG3 is a human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0302] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody specifically binds to FXIIa. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0303] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-9 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 10-33 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 34-50 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs:51-64 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs:65-73 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs:74-88 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0304] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG2 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-9 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 10-33 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 34-50 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs:51-64 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs:65-73 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs:74-88 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG2 is a human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0305] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG3 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-9 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions, an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 10-33 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 34-50 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: NOs:51-64 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; LC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs:65-73 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids; and LC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs:74-88 or a variant thereof, the variant comprising a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG3 is a human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0306] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 1-9 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; an HC-CDR2 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 10-33 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and an HC-CDR3 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 34-50 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions; and b) a light chain variable domain comprising: an LC-CDR1 comprising an amino acid sequence as shown in any one of SEQ ID NOs: 35-37 or a variant thereof, wherein the variant comprises up to about 3 (e.g., 1, 2, or 3) amino acid substitutions. NOs:51-64 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, LC-CDR2, comprising an amino acid sequence as set forth in any one of SEQ ID NOs:65-73 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids, and LC-CDR3, comprising an amino acid sequence as set forth in any one of SEQ ID NOs:74-88 or a variant thereof, wherein the variant comprises a substitution of up to about 3 (e.g., 1, 2, or 3) amino acids. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO:160.

[0307] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-9, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-33, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 34-50, or a variant of the heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 51-64, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 65-73, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NOs: The amino acid sequence shown in any one of NOs:74-88, or a variant of the light chain variable domain, comprises a substitution of up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acids in its LC-CDR sequence. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0308] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-9, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-33, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 34-50, or a variant of the heavy chain variable domain comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions in the HC-CDR sequence; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 51-64, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 65-73, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NOs: NOs: 74-88, or a variant of the light chain variable domain, comprising a substitution of up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acids in its LC-CDR sequence. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0309] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-9, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-33, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 34-50; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 51-64, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 65-73, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 74-88. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0310] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 1-9, an HC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 10-33, and an HC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 34-50; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of any one of SEQ ID NOs: 51-64, an LC-CDR2 comprising the amino acid sequence of any one of SEQ ID NOs: 65-73, and an LC-CDR3 comprising the amino acid sequence of any one of SEQ ID NOs: 74-88. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0311] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0312] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0313] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0314] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0315] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 54, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0316] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0317] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0318] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0319] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0320] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 17, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0321] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0322] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0323] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 55, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 77. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0324] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0325] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0326] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 18, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0327] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0328] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0329] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0330] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 20, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0331] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 19, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0332] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0333] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0334] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 41; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0335] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 56, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 78. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0336] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0337] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 22, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0338] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 42; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0339] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0340] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 23, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0341] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0342] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 25, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0343] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 79. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0344] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0345] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 21, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0346] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 2, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 26, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 43; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 57, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 66, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 81. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0347] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 3, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 44; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 58, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 67, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 82. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0348] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 4, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 45; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 59, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 68, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 83. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0349] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 5, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 29, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 46; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 60, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 69, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 84. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0350] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 6, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 30, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 47; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 61, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 70, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 85. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0351] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 7, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 31, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 48; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 62, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 71, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 86. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0352] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 8, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 32, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 49; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 63, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 72, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 87. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0353] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG1 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 9, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 33, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 50; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 64, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 73, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 88. In some embodiments, the IgG1 is a human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 157 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0354] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 10, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 51, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 74. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0355] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 11, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0356] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 12, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0357] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 53, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0358] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 14, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 54, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0359] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 15, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0360] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 13, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0361] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 16, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and b) a light chain variable domain comprising: an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 52, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 65, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 75. In some embodiments, the IgG4 is a human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 159. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 158 and the light chain constant region comprises or consists of the amino acid sequence of SEQ ID NO: 160.

[0362] In some embodiments, a full-length anti-FXIIa antibody comprising an IgG4 constant region is provided, wherein the anti-FXIIa antibody comprises: a) a heavy chain variable domain comprising: an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 1, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO...

Claims

1. An isolated anti-FXIIa antibody, wherein the anti-FXIIa antibody comprises: Heavy chain variable domain (V H ), the V H Include: heavy chain complementarity determining region (HC-CDR) 1, comprising SQTMS (SEQ ID NO: 1); HC-CDR2, which contains SX 1 X 2 X 3 ISX 4 RX 5 YYADSVKG (SEQ ID NO: 89), wherein X 1 I or S, X 2 H or S, X 3 H, V or Y, X 4 is G, K or R, X 5 is A, D, K, M, N, P, R, S, T, or Y; and HC-CDR3, which comprises X 1 HX 2 FDX 3 (SEQ ID NO:90), wherein X 1 A, G, H, Q, S or W, X 2 A, D or R, X 3 is L or V; and Light chain variable domain (V L ), the V L Include: Light chain complementarity determining region (LC-CDR) 1, which contains RASQSX 1 X 2 X 3 X 4 LA (SEQ ID NO: 91), wherein X 1 L or V, X 2 is F, W or Y, X 3 S or Y, X 4 is A, H or N; LC-CDR2 comprising GASTRAT (SEQ ID NO:65); and LC-CDR3, which contains QQX 1 X 2 X 3 WPLS (SEQ ID NO: 92), wherein X 1 N or Y, X 2 is H, K, N or Q, X 3 K, R or W.

2. The isolated anti-FXIIa antibody according to claim 1, comprising: (i)V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:74; (ii) V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (iii)V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:52, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:76; (iv)V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (v)V H , the 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: 14, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (vi)V H , the 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: 15, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (vii) V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (viii)V H , the 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: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (ix)V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:53, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:75; (x)V H , the 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: 17, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xi)V H , the 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: 16, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xii)V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 36; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xiii)V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 37; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:55, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:77; (xiv)V H , the 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: 11, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:51, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xv)V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 38; and V L , the V L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:52, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:76; (xvi)V H , the 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: 18, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xvii)V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xviii)V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xix)V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 40; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xx)V H , the 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: 20, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxi)V H , the 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: 19, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L Comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:53, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:75; (xxii)V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxiii)V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxiv)V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 41; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxv)V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:56, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:78; (xxvi)V H , the 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: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxvii)V H , the 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: 22, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L Contains: LC-CDR1, which comprises amino acids sequence SEQ ID NO:52, LC-CDR2, which comprises the amino acid sequence SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence SEQ ID NO:75; (xxviii)V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 42; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:76; (xxix)V H , the 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: 10, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 35; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxx)V H , the 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: 23, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxxi)V H , the 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: 24, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxxii)V H , the 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: 25, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L comprising: LC-CDR1 comprising the amino acid sequence of SEQ ID NO:52, LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and LC-CDR3 comprising the amino acid sequence of SEQ ID NO:75; (xxxiii)V H , the 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: 12, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L Contains: LC-CDR1, which comprises amino acids sequence SEQ ID NO:52, LC-CDR2, which comprises the amino acid sequence SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence SEQ ID NO:79; (xxxiv)V H , the 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: 13, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 39; and V L , the V L comprising: a LC-CDR1 comprising the amino acid sequence of SEQ ID NO:53, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO:65, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO:80; or (xxxv)V H , the 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: 21, and HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 34; and V L , the V L It comprises: LC-CDR1, which comprises the amino acid sequence of SEQ ID NO:52, LC-CDR2, which comprises the amino acid sequence of SEQ ID NO:65, and LC-CDR3, which comprises the amino acid sequence of SEQ ID NO:

75.

3. The isolated anti-FXIIa antibody according to any one of claims 1-2, comprising: (i)V H , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; and V L , comprising the amino acid sequence of SEQ ID NO: 139 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 139; (ii) V H , comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (iii)V H , comprising the amino acid sequence of SEQ ID NO: 95 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 95; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (iv)V H , comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 96; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (v)V H , comprising the amino acid sequence of SEQ ID NO: 97 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 97; and V L , comprising the amino acid sequence of SEQ ID NO: 143 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 143; (vi)V H , comprising the amino acid sequence of SEQ ID NO: 98 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 98; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (vii) V H , comprising the amino acid sequence of SEQ ID NO: 96 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 96; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (viii)V H , comprising the amino acid sequence of SEQ ID NO: 99 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 99; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (ix)V H , comprising the amino acid sequence of SEQ ID NO: 94 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 94; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (x)V H , comprising the amino acid sequence of SEQ ID NO: 100 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 100; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xi)V H , comprising the amino acid sequence of SEQ ID NO: 101 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 101; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xii)V H , comprising the amino acid sequence of SEQ ID NO: 102 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 102; and V L , which comprises the amino acid sequence SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 142; (xiii)V H , comprising the amino acid sequence of SEQ ID NO: 103 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 103; and V L , comprising the amino acid sequence of SEQ ID NO: 144 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 144; (xiv)V H , comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 104; and V L , comprising the amino acid sequence of SEQ ID NO: 145 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 145; (xv)V H , comprising the amino acid sequence of SEQ ID NO: 105 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 105; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (xvi)V H , comprising the amino acid sequence of SEQ ID NO: 106 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 106; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xvii)V H , comprising the amino acid sequence of SEQ ID NO: 107 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 107; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xviii)V H , comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xix)V H , comprising the amino acid sequence of SEQ ID NO: 109 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 109; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xx)V H , comprising the amino acid sequence of SEQ ID NO: 110 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 110; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxi)V H , comprising the amino acid sequence of SEQ ID NO: 111 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 111; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxii)V H , comprising the amino acid sequence of SEQ ID NO: 112 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 112; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (xxiii)V H , comprising the amino acid sequence of SEQ ID NO: 113 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 113; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxiv)V H , comprising the amino acid sequence of SEQ ID NO: 114 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 114; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxv)V H , comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxvi)V H , comprising the amino acid sequence of SEQ ID NO: 93 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 93; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxvii)V H , comprising the amino acid sequence of SEQ ID NO: 115 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 115; and V L , which contains amino acids The sequence SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence SEQ ID NO: 140; (xxviii)V H , comprising the amino acid sequence of SEQ ID NO: 116 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 116; and V L , comprising the amino acid sequence of SEQ ID NO: 146 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 146; (xxix)V H , comprising the amino acid sequence of SEQ ID NO: 117 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 117; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxx)V H , comprising the amino acid sequence of SEQ ID NO: 118 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 118; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxi)V H , comprising the amino acid sequence of SEQ ID NO: 104 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 104; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxxii)V H , comprising the amino acid sequence of SEQ ID NO: 119 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 119; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxiii)V H , comprising the amino acid sequence of SEQ ID NO: 120 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 120; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxiv)V H , comprising the amino acid sequence of SEQ ID NO: 111 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 111; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxxv)V H , comprising the amino acid sequence of SEQ ID NO: 121 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 121; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxvi)V H , comprising the amino acid sequence of SEQ ID NO: 122 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 122; and V L , comprising the amino acid sequence of SEQ ID NO: 141 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 141; (xxxvii)V H , comprising the amino acid sequence of SEQ ID NO: 123 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 123; and V L , comprising the amino acid sequence of SEQ ID NO: 142 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 142; (xxxviii)V H , comprising the amino acid sequence of SEQ ID NO: 124 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 124; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xxxix)V H , comprising the amino acid sequence of SEQ ID NO: 125 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 125; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xl)V H , comprising the amino acid sequence of SEQ ID NO: 126 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 126; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xli)V H , comprising the amino acid sequence of SEQ ID NO: 112 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 112; and V L , comprising the amino acid sequence of SEQ ID NO: 147 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 147; (xlii)V H , comprising the amino acid sequence of SEQ ID NO: 108 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 108; and V L , which comprises the amino acid sequence SEQ ID NO: 148 or a variant thereof, wherein the variant has at least 80% sequence identity to the amino acid sequence of SEQ ID NO: 148; (xliii)V H , comprising the amino acid sequence of SEQ ID NO: 127 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 127; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xliv)V H , comprising the amino acid sequence of SEQ ID NO: 128 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 128; and V L , comprising the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; (xlv)V H , comprising the amino acid sequence of SEQ ID NO: 129 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 129; and V L , which comprises the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 140; or (xlvi)V H , comprising the amino acid sequence of SEQ ID NO: 130 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO: 130; and V L , which comprises the amino acid sequence of SEQ ID NO: 140 or a variant thereof, wherein the variant has at least 80% sequence identity with the amino acid sequence of SEQ ID NO:

140. 4 . The isolated anti-FXIIa antibody according to any one of claims 1 to 3 , wherein the anti-FXIIa antibody binds to human FXIIa with a Kd value of 0.1 pM to 1 nM.

5. The isolated anti-FXIIa antibody according to any one of claims 1 to 4, wherein the anti-FXIIa antibody comprises an Fc fragment.

6. The isolated anti-FXIIa antibody according to claim 5, wherein the anti-FXIIa antibody is a full-length IgA, IgD, IgE, IgG or IgM antibody.

7. The isolated anti-FXIIa antibody according to claim 6, wherein the anti-FXIIa antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody.

8. The isolated anti-FXIIa antibody according to any one of claims 1 to 7, wherein the anti-FXIIa antibody is a chimeric, human or humanized antibody.

9. The isolated anti-FXIIa antibody according to any one of claims 1 to 4, wherein the anti-FXIIa antibody is an antigen-binding fragment selected from the group consisting of Fab, Fab', F(ab)' 2 , Fab'-SH, single-chain Fv (scFv), Fv fragment, dAb, Fd, nanobody, diabody and linear antibody.

10. An isolated nucleic acid molecule encoding the anti-FXIIa antibody of any one of claims 1-9.

11. A vector comprising the nucleic acid molecule of claim 10. 12 . An isolated host cell comprising the anti-FXIIa antibody of any one of claims 1 to 9 , the nucleic acid molecule of claim 10 , or the vector of claim 11 .

13. A method for preparing an anti-FXIIa antibody, comprising: a) culturing the host cell of claim 12 under conditions effective for expressing the anti-FXIIa antibody; and b) obtaining the expressed anti-FXIIa antibody from the host cells.

14. A pharmaceutical composition comprising the anti-FXIIa antibody of any one of claims 1 to 9, the nucleic acid molecule of claim 10, the vector of claim 11, the isolated host cell of claim 12 or the antibody prepared by the method of claim 13, and a pharmaceutically acceptable carrier.

15. Use of the antibody of any one of claims 1 to 9, the nucleic acid molecule of claim 10, the vector of claim 11, the host cell of claim 12, the antibody prepared by the method of claim 13, or the pharmaceutical composition of claim 14 in the preparation of a medicament for treating a disease or condition in an individual in need thereof, wherein the disease or condition is a disease and / or condition caused by dysregulation of the FXIIa signaling pathway, such as thrombosis, diseases associated with FXII / FXIIa-induced kinin formation, diseases associated with FXII / FXIIa-induced complement activation, diseases associated with the contact activation system, and diseases associated with inflammation.

16. The method of claim 15, wherein the disease or condition is selected from the group consisting of venous, arterial or capillary thrombosis, intracardiac thrombosis, thrombosis during and / or after contacting the blood of a human or animal subject with an artificial surface, thromboembolism, atherosclerosis, interstitial lung disease, inflammation, neuroinflammatory diseases, neurotraumatic diseases, traumatic brain injury, complement activation, fibrinolysis, angiogenesis, hereditary angioedema (HAE), bacterial pulmonary infection, trypanosoma infection, hypotensive shock, pancreatitis, chagas disease, arthritis, arthritis, disseminated intravascular coagulation and sepsis, macular edema, diabetic retinopathy, hypertensive retinopathy, age-related macular degeneration, retinal vein occlusion, organ ischemia, distal ischemia-reperfusion injury (IRI), chronic kidney disease, renal fibrosis, multiple sclerosis.

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