Dual inhibitor trypsin antibodies and uses thereof

Abstract

Aspects of the application provide dual inhibitor anti-trypsin 1 / trypsin 2 antibodies and methods of using the same for treating pancreatitis. Other aspects of the application provide engineered non-human organisms encoding a human trypsin 1 protein.

Description

DUAL INHIBITOR TRYPSIN ANTIBODIES AND USES THEREOFRELATED APPLICATIONS

[0001] This application claims the benefit under 35 U. S. C. § 119(e) of U. S. Provisional Application Serial No. 63 / 708,239, entitled “DUAL INHIBITOR TRYPSIN ANTIBODIES AND USES THEREOF” and filed on October 16, 2024; U. S. Provisional Application Serial No.63 / 725,853. entitled “DUAL INHIBITOR TRYPSIN ANTIBODIES AND USES THEREOF” and filed on November 27, 2024; and U. S. Provisional Application Serial No. 63 / 836,842, entitled “DUAL INHIBITOR TRYPSIN ANTIBODIES AND USES THEREOF” and filed on July 1, 2025, the entire contents of each of which are incorporated herein by reference in their entirety for all purposes.REFERENCE TO AN ELECTRONIC SEQUENCE LISTING

[0002] The contents of the electronic sequence listing (A140770012WO00-SEQ-KGC.xml; Size: 283,945 bytes; and Date of Creation: October 7, 2025) are herein incorporated by reference in their entirety.BACKGROUND

[0003] Pancreatitis is an inflammatory disease of the pancreas, which can be an acute or chronic condition. In certain cases, pancreatitis can be associated with genetic abnormalities that may be inherited or spontaneously arising. However, there are other causes, including heavy alcohol use, gallstones, treatment with certain medicines, and still others. Effective treatment options remain limited, and consequently, pancreatitis can result in significant morbidity and mortality.SUMMARY

[0004] Certain aspects of the disclosure relate to a recognition that activation of trypsin (e.g., trypsin 1 and trypsin 2) in the pancreas is associated with the development of pancreatitis. In some embodiments, methods and related compositions are provided that are useful for inhibition of trypsin 1 and trypsin 2 for purposes of treating pancreatitis. In particular, aspects of the disclosure provide dual inhibitor antibodies targeting trypsin 1 and trypsin 2 (referred to as anti-trypsin 1 / trypsin 2 antibodies) that have high binding affinity and specificity to both trypsin 1and trypsin 2 via a common distinct antigen-specific binding site. Accordingly, in some embodiments, the disclosure provides methods and related antibody compositions for treating conditions associated with trypsin 1 and trypsin 2 dysregulation, such as hereditary pancreatitis, acute pancreatitis, recurrent acute pancreatitis, or chronic pancreatitis.

[0005] Provided herein, in some aspects, is a dual inhibitor antibody that specifically bind to trypsin 1 and trypsin 2, the dual inhibitor antibody comprising: (a) a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), HC CDR2, and HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 57, and a light chain (LC) complementarity determining region (CDR) 1 (LC CDRl), LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 58; (b) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 59, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 60; (c) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 61, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 62; (d) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 63, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 64; (e) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 65, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 66; (f) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 67, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 68; (g) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 166, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 66; (h) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 69, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70; (i) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 71, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70; (j) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 72, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73; (k) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 74, and a LCCDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73; (1) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 75, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73; (m) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 76, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73; (n) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 77, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 78; (o) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 79, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 80; (p) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 81, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 82; (q) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 203, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204; (r) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 217, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204; (s) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 83, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70; (t) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 84, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70; (u) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 233, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70; or (v) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 237, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73; and a heavy chain constant region that comprises: one or more substitutions that reduce effector function; and one or more substitutions that extend serum half-life.

[0006] In some embodiments, the one or more substitutions that reduce effector function are substitutions at L234, L235, and / or P329 according to the EU numbering. In some embodiments, the one or more substitutions that reduce effector function are L234A, L235A, and / or P329Aaccording to the EU numbering. In some embodiments, the heavy chain constant region comprises L234A, L235A, and P329A substitutions according to the EU numbering.

[0007] In some embodiments, the one or more substitutions that extend serum half-life are substitutions at M428, N434S, M252, S254, and / or T256 according to the EU numbering. In some embodiments, one or more substitutions that extend serum half-life are M428L, N434S, M252Y, S254T, and / orT256E according to the EU numbering. In some embodiments, the one or more substitutions that extend serum half-life are M428L, N434A, M252Y, S254T, and / or T256E according to the EU numbering. In some embodiments, wherein the heavy chain constant region comprises: (i) M428L and N434A according to the EU numbering; (ii) M428L and N434S according to the EU numbering; or (iii) M252Y, S254T, and T256E according to the EU numbering.

[0008] In some embodiments, wherein the heavy chain constant region comprises L234A, L235A, P329A, M428L and N434A substitutions according to the EU numbering.

[0009] In some embodiments, the heavy chain constant regions comprises the amino acid sequence of SEQ ID NO: 229. In some embodiments, the heavy chain constant region comprises L234A, L235A, P329A, M428L and N434S substitutions according to the EU numbering.

[0010] In some embodiments, the heavy chain constant regions comprises the amino acid sequence of SEQ ID NO: 230. In some embodiments, the heavy chain constant region comprises L234A, L235A, P329A, M252Y, S254T, and T256E substitutions according to the EU numbering.

[0011] In some embodiments, the heavy chain constant regions comprises the amino acid sequence of SEQ ID NO: 231.

[0012] In some embodiments, the dual inhibitor antibody comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 7, a HC CDR2 having the amino acid sequence of SEQ ID NO: 8, a HC CDR3 having the amino acid sequence of SEQ ID NO: 9, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 10; (c) a HCCDR1 having the amino acid sequence of SEQ ID NO: 11, a HC CDR2 having the amino acid sequence of SEQ ID NO: 12, a HC CDR3 having the amino acid sequence of SEQ ID NO: 13, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 16; (d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 17, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 19, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 20; (e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 23, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24; (f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 25, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 26; (g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 165, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24; (h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 27, a HC CDR2 having the amino acid sequence of SEQ ID NO: 28, a HC CDR3 having the amino acid sequence of SEQ ID NO: 29, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32; (i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 33, a HC CDR2 having the amino acid sequence of SEQ ID NO: 34, a HC CDR3 having the amino acid sequence of SEQ ID NO: 35, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32; (j) a HC CDRl having the amino acid sequence of SEQ ID NO: 36, a HC CDR2 having the amino acid sequence of SEQ ID NO: 37, a HC CDR3 having the amino acidsequence of SEQ ID NO: 38, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39; (k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 38, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, find a LC CDR3 having the amino acid sequence of SEQ ID NO: 39; (1) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39; (m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 43, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39; (n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 44, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 45; (o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 46, a HC CDR3 having the amino acid sequence of SEQ ID NO: 47, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48; (p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 having the amino acid sequence of SEQ ID NO: 50, a HC CDR3 having the amino acid sequence of SEQ ID NO: 51, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 52; (q) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 202, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the aminoacid sequence of SEQ ID NO: 48; (r) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 216, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48; (s) a HC CDR1 having the amino acid sequence of SEQ ID NO: 27, a HC CDR2 having the amino acid sequence of SEQ ID NO: 28, a HC CDR3 having the amino acid sequence of SEQ ID NO: 53, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32; or (t) a HC CDR1 having the amino acid sequence of SEQ ID NO: 54, a HC CDR2 having the amino acid sequence of SEQ ID NO: 55, a HC CDR3 having the amino acid sequence of SEQ ID NO: 56, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32.

[0013] In some embodiments, the dual inhibitor antibody comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 57, and a VL comprising the amino acid sequence of SEQ ID NO: 58; (b) a VH comprising the amino acid sequence of SEQ ID NO: 59, and a VL comprising the amino acid sequence of SEQ ID NO: 60; (c) a VH comprising the amino acid sequence of SEQ ID NO: 61, and a VL comprising the amino acid sequence of SEQ ID NO: 62; (d) a VH comprising the amino acid sequence of SEQ ID NO: 63, and a VL comprising the amino acid sequence of SEQ ID NO: 64; (e) a VH comprising the amino acid sequence of SEQ ID NO: 65, and a VL comprising the amino acid sequence of SEQ ID NO: 66; (f) a VH comprising the amino acid sequence of SEQ ID NO: 67, and a VL comprising the amino acid sequence of SEQ ID NO: 68; (g) a VH comprising the amino acid sequence of SEQ ID NO: 166, and a VL comprising the amino acid sequence of SEQ ID NO: 66; (h) a VH comprising the amino acid sequence of SEQ ID NO: 69, and a VL comprising the amino acid sequence of SEQ ID NO: 70; (i) a VH comprising the amino acid sequence of SEQ ID NO: 71, and a VL comprising the amino acid sequence of SEQ ID NO: 70; (j) a VH comprising the amino acid sequence of SEQ ID NO: 72, and a VL comprising the amino acid sequence of SEQ ID NO: 73; (k) a VH comprising the amino acid sequence of SEQ ID NO: 74, and a VL comprising the amino acid sequence of SEQ ID NO: 73; (1) a VH comprising the amino acid sequence of SEQ ID NO: 75, and a VL comprising the amino acid sequence of SEQ ID NO: 73; (m) a VHcomprising the amino acid sequence of SEQ ID NO: 76, and a VL comprising the amino acid sequence of SEQ ID NO: 73; (n) a VH comprising the amino acid sequence of SEQ ID NO: 77, and a VL comprising the amino acid sequence of SEQ ID NO: 78; (o) a VH comprising the amino acid sequence of SEQ ID NO: 79, and a VL comprising the amino acid sequence of SEQ ID NO: 80; (p) a VH comprising the amino acid sequence of SEQ ID NO: 81, and a VL comprising the amino acid sequence of SEQ ID NO: 82; (q) a VH comprising the amino acid sequence of SEQ ID NO: 203, and a VL comprising the amino acid sequence of SEQ ID NO: 204; (r) a VH comprising the amino acid sequence of SEQ ID NO: 217, and a VL comprising the amino acid sequence of SEQ ID NO: 204; (s) a VH comprising the amino acid sequence of SEQ ID NO: 83, and a VL comprising the amino acid sequence of SEQ ID NO: 70; (t) a VH comprising the amino acid sequence of SEQ ID NO: 84, and a VL comprising the amino acid sequence of SEQ ID NO: 70; (u) a VH comprising the amino acid sequence of SEQ ID NO: 223, and a VL comprising the amino acid sequence of SEQ ID NO: 70; or (v) a VH comprising the amino acid sequence of SEQ ID NO: 237, and a VL comprising the amino acid sequence of SEQ ID NO: 73.

[0014] In some embodiments, the dual inhibitor antibody further comprises a light chain constant region. In some embodiments, the light chain constant region comprises the amino acid sequence of SEQ ID NO: 232.

[0015] Provided herein, in some aspects, is a dual inhibitor antibody that specifically binds trypsin 1 and trypsin 2, the dual inhibitor antibody comprising: (a) a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), a HC CDR2, a HC CDR3, a light chain (LC) complementarity determining region (CDR) 1 (LC CDR1), a LC CDR2, and / or a LC CDR3 of any one of the antibodies listed in I' able la and Table lb; or (b) a heavy chain variable domain (VH) and / or a light chain variable domain (VL) of any one of the antibodies listed in Table la; and a heavy chain constant region comprising: a L234A, L235A, and P329A substitution according to the EU numbering, and: (i) M428L and N434A substitutions according to the EU numbering; (ii) M428L and N434S substitutions according to the EU numbering; or (iii) M252Y / S254T / T256E substitutions according to the EU numbering.

[0016] In some embodiments, the dual inhibitor antibody comprises: (a) a heavy chain (HC) comprising the amino acid sequence of any one of SEQ ID NOs: 141-143; and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 144; (b) a HC comprising the amino acidsequence of any one of SEQ ID NOs: 145-147; and a LC comprising the amino acid sequence of SEQ ID NO: 148; (c) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 149-151; and a LC comprising the amino acid sequence of SEQ ID NO: 152; (d) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 153-155; and a LC comprising the amino acid sequence of SEQ ID NO: 156; (e) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 157-159; and a LC comprising the amino acid sequence of SEQ ID NO: 160; (f) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 161-163; and a LC comprising the amino acid sequence of SEQ ID NO: 164; (g) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 167-169; and a LC comprising the amino acid sequence of SEQ ID NO: 160; (h) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 170-172; and a LC comprising the amino acid sequence of SEQ ID NO: 173; (i) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 174-176; and a LC comprising the amino acid sequence of SEQ ID NO: 173; (j) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 177-179; and a LC comprising the amino acid sequence of SEQ ID NO: 180; (k) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 181-183; and a LC comprising the amino acid sequence of SEQ ID NO: 180; (I) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 184-186; and a LC comprising the amino acid sequence of SEQ ID NO: 180; (m) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 187-189; and a LC comprising the amino acid sequence of SEQ ID NO: 180; (n) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 190-192; and a LC comprising the amino acid sequence of SEQ ID NO: 193; (o) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 194-196; and a LC comprising the amino acid sequence of SEQ ID NO: 197; (p) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 198-200; and a LC comprising the amino acid sequence of SEQ ID NO: 201; (q) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 205-207; and a LC comprising the amino acid sequence of SEQ ID NO: 208; (r) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 218-220; and a LC comprising the amino acid sequence of SEQ ID NO: 208; (s) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 209-212; and a LC comprising the amino acid sequence of SEQ ID NO: 173; (t) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 213-215; and a LC comprising the amino acid sequence of SEQ ID NO: 173; (u) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 234-236;and a LC comprising the amino acid sequence of SEQ ID NO: 173; or (v) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 238-240; and a LC comprising the amino acid sequence of SEQ ID NO: 173.

[0017] In some embodiments, the dual inhibitor antibody binds to the active site of trypsin 1 and the active site of trypsin 2.

[0018] In some embodiments, the dual inhibitor antibody binds to an active form of trypsin 1 and an active form of trypsin 2 but does not bind to an inactive form of trypsin 1 or the inactive form of trypsin 2. In some embodiments, the dual inhibitor antibody inhibits protease activity of trypsin 1 and / or trypsin 2.

[0019] In some embodiments, the dual inhibitor antibody is not cleaved in the heavy chain by trypsin 1 and / or trypsin 2 on binding to trypsin 1 and trypsin 2.

[0020] In some embodiments, the dual inhibitor antibody is cleaved in the heavy chain by trypsin 1 and / or trypsin 2 on binding to trypsin 1 and / or trypsin 2 but remains bound to trypsin 1 and trypsin 2.

[0021] In some embodiments, the dual inhibitor antibody inhibits protease activity of trypsin 1 and / or trypsin 2 after being cleaved in the heavy chain by trypsin 1 and / or trypsin 2 on binding to trypsin 1 and trypsin 2.

[0022] Provided herein, in some aspects, is a dual inhibitor antibody that specifically binds trypsin 1 and trypsin 2, the dual inhibitor antibody comprising: (a) a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), a HC CDR2, and a HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 166, and a light chain (LC) complementarity determining region (CDR) 1 (LC CDR1), LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 66; (b) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 203, and a LC CDR1, LC CDR2,and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204; or (c) a HC CDR1, HC CDR2 and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 217, and a LC CDR1, LC CDR2 and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204.

[0023] In some embodiments, the dual inhibitor antibody comprises: (a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 165, a LC CDR1having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24; (b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 202, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48; or (c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 216, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48.

[0024] In some embodiments, the dual inhibitor antibody comprises: (a) a VH comprising the amino acid sequence of SEQ ID NO: 166, and a VL comprising the amino acid sequence of SEQ ID NO: 66; (b) a VH comprising the amino acid sequence of SEQ ID NO: 203, and a VL comprising the amino acid sequence of SEQ ID NO: 204; or (c) a VH comprising the amino acid sequence of SEQ ID NO: 217, and a VL comprising the amino acid sequence of SEQ ID NO: 204.

[0025] In some embodiments, the dual inhibitor antibody further comprises a heavy chain constant region that comprises: one or more substitutions that reduce effector function; and one or more substitutions that extend serum half-life.

[0026] Provided herein, in some aspects, is an isolated nucleic acid comprising a nucleic acid sequence encoding the VH and / or the VL, or the HC and / or the LC of a dual inhibitor antibody provided herein.

[0027] In some embodiments, the isolated nucleic acid comprises: (a) a nucleic acid sequence of SEQ ID NO: 105, and / or a nucleic acid sequence of SEQ ID NO: 106; (b) a nucleic acid sequence of SEQ ID NO: 107, and / or a nucleic acid sequence of SEQ ID NO: 108; (c) a nucleic acid sequence of SEQ ID NO: 109, and / or a nucleic acid sequence of SEQ ID NO: 110; (d) a nucleic acid sequence of SEQ ID NO: 111, and / or a nucleic acid sequence of SEQ ID NO: 112; (e) a nucleic acid sequence of SEQ ID NO: 113, and / or a nucleic acid sequence of SEQ ID NO: 114; (f) a nucleic acid sequence of SEQ ID NO: 115, and / or a nucleic acid sequence of SEQ ID NO: 116; (g) a nucleic acid sequence of SEQ ID NO: 221, and / or a nucleic acid sequence ofSEQ ID NO: 222; (h) a nucleic acid sequence of SEQ ID NO: 117, and / or a nucleic acid sequence of SEQ ID NO: 118; (i) a nucleic acid sequence of SEQ ID NO: 119, and / or a nucleic acid sequence of SEQ ID NO: 120; (j) a nucleic acid sequence of SEQ ID NO: 121, and / or a nucleic acid sequence of SEQ ID NO: 122; (k) a nucleic acid sequence of SEQ ID NO: 123, and / or a nucleic acid sequence of SEQ ID NO: 124; (1) a nucleic acid sequence of SEQ ID NO: 125, and / or a nucleic acid sequence of SEQ ID NO: 126; (m) a nucleic acid sequence of SEQ ID NO: 127, and / or a nucleic acid sequence of SEQ ID NO: 128; (n) a nucleic acid sequence of SEQ ID NO: 129, and / or a nucleic acid sequence of SEQ ID NO: 130; (o) a nucleic acid sequence of SEQ ID NO: 131, and / or a nucleic acid sequence of SEQ ID NO: 132; (p) a nucleic acid sequence of SEQ ID NO: 133, and / or a nucleic acid sequence of SEQ ID NO: 134; (q) a nucleic acid sequence of SEQ ID NO: 223, and / or a nucleic acid sequence of SEQ ID NO: 224; (r) a nucleic acid sequence of SEQ ID NO: 225 and / or a nucleic acid sequence of SEQ ID NO: 226; (s) a nucleic acid sequence of SEQ ID NO: 135, and / or a nucleic acid sequence of SEQ ID NO: 136; or (t) a nucleic acid sequence of SEQ ID NO: 137, and / or a nucleic acid sequence of SEQ ID NO: 138.

[0028] Provided herein, in some aspects, is an expression vector comprising an isolated nucleic acid provided herein.

[0029] Provided herein, in some aspects, is a host cell comprising dual inhibitor antibody, an isolated nucleic acid, or an expression vector provided herein. In some embodiments, the host cell is a CHO cell, or a HEK293 cell.

[0030] Provided herein, in some aspects is a method for producing a dual inhibitor antibody provided herein, the method comprising: (i) culturing a host cell provided herein under conditions for expressing the dual inhibitor antibody; and (ii) harvesting the dual inhibitor antibody from a host cell lysate or culture supernatant.

[0031] In some embodiments, the method further comprises purifying the dual inhibitor antibody.

[0032] Provided herein, in some aspects, is a composition comprising a dual inhibitor antibody, an isolated nucleic acid, an expression vector or a cell provided herein. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier.

[0033] Provided herein, in some aspects, is method of treating pancreatitis, the method comprising administering to a subject in need thereof an effective amount of a dual inhibitorantibody, an isolated nucleic acid, an expression vector, a cell, or a composition provided herein. In some embodiments, the subject has hereditary pancreatitis, acute pancreatitis, recurrent acute pancreatitis, or chronic pancreatitis.

[0034] Provided herein, in some aspects, is a method of treating pancreatitis, the method comprising administering to a subject in need thereof an effective amount of at least one antibody that specifically binds to trypsin 1 and / or trypsin 2.

[0035] In some embodiments, the at least one antibody specifically binds to trypsin 1. In some embodiments, the at least one antibody specifically binds to the active site of trypsin 1. In some embodiments, the at least one antibody inhibits protease activity of trypsin 1.

[0036] In some embodiments, the at least one antibody specifically binds to trypsin 2. In some embodiments, the at least one antibody specifically binds to the active site of trypsin 2. In some embodiments, the at least one antibody inhibits protease activity of trypsin 2.

[0037] In some embodiments, the method further comprises administering to the subject at least one antibody that specifically binds to trypsin 1 and trypsin 2 and inhibits their respective protease activities. In some embodiments, the at least one antibody is a dual inhibitor antibody that specifically binds to trypsin 1 and trypsin 2.

[0038] In some embodiments, the subject has hereditary pancreatitis, acute pancreatitis, recurrent acute pancreatitis, or chronic pancreatitis.

[0039] Provided herein, in some aspects, is a method for treating hereditary pancreatitis (HP), the method comprising administering to a subject having (HP) an amount of an anti-trypsin 1 / trypsin 2 antibody effective for inhibiting trypsin 1 and / or trypsin 2 protease activity, regardless of if the subject is having a flare-up episode, hi some embodiments, wherein the administration reduces pancreas tissue damage. In some embodiments, the administration reduces pancreas cell death. In some embodiments, the administration reduces pancreas edema.

[0040] Provided herein, in some aspects, is a polypeptide comprising a sequence as set forth in SEQ ID NO: 103 or a fragment thereof suitable for generating an antibody that specifically binds to and inhibits protease activity of trypsin 1, optionally wherein the polypeptide comprises a tag, such as a His-tag.

[0041] Provided herein, in some aspects, is a polypeptide comprising a sequence as set forth in SEQ ID NO: 104 or a fragment thereof suitable for generating an antibody that specificallybinds to and inhibits protease activity of trypsin 2. optionally wherein the polypeptide comprises a tag, such as a His-tag.

[0042] Provided herein, in some aspects, is a method of obtaining a dual inhibitor anti-trypsin 1 / trypsin 2 antibody, the method comprising: generating an antibody that (i) specifically binds to the polypeptide of claim 46 and inhibits protease activity of trypsin 1; and (ii) specifically binds to the polypeptide of claim 47 and inhibits protease activity of trypsin 2; thereby obtaining a dual inhibitor anti-trypsin 1 / trypsin 2 antibody.

[0043] Provided herein, in some aspects, is an engineered non-human organism comprising in its genome an engineered nucleic acid encoding a human trypsin 1 protein that is operably linked to fin endogenous promoter of the non-human organism.

[0044] In some embodiments, the endogenous promoter is a promoter of a homolog of the human PRSS l gene in the non-human organism.

[0045] Tn some embodiments, the engineered non-human organism is a mouse. In some embodiments, the homolog is a mouse cationic trypsinogen T7 gene.

[0046] In some embodiments, wherein the human trypsin 1 protein comprises an amino acid substitution associated with hereditary pancreatitis. In some embodiments, the amino acid substitution is R122H.

[0047] In some embodiments, the engineered nucleic acid encoding the human trypsin 1 protein comprises the nucleic acid sequence set forth in SEQ ID NO: 227.

[0048] Provided herein, in some aspects, is a method of selecting an antibody that specifically binds to trypsin 1 and / or trypsin 2, the method comprising: (i) generating a set of antibodies that specifically binds trypsin 1 and / or trypsin 2; (ii) selecting an antibody that comprises a heavy chain complementarity determining region 3 (HC CDR3) in the range of 16-22 amino acid residues in length from the set of antibodies generated in step (i); and (iii) determining that the HC CDR3 of the selected antibody forms a loop that fits into an active site of trypsin 1 and / or trypsin 2.

[0049] Provided herein, in some aspects, is a method of selecting an antibody that specifically binds to trypsin 1 and / or trypsin 2, the method comprising: (i) selecting an antibody that comprises a HC CDR3 in the range of 16-22 amino acid residues in length from a set of antibodies identified as specifically binding to trypsin 1 and / or trypsin 2 enzyme; and (ii)determining that the HC CDR3 of the selected antibody forms a loop that fits into an active site of trypsin 1 and / or trypsin 2.

[0050] In some embodiments, the determining of step (ii) is performed by modeling the three- dimensional structure of the antibody.

[0051] In some embodiments, the HC CDR3 of the selected antibody is in the range of 19-20 amino acid residues in length. In some embodiments, in the set of antibodies, the HC CDR3s comprise, on average, fewer than 16 amino acids.

[0052] In some embodiments, the CDRs of the antibodies are determined by Kabat, Chothia, or IMGT.

[0053] Provided herein, in some aspects, is an antibody selected from a method of selecting an antibody that specifically binds to trypsin 1 and / or trypsin 2, as provided herein.

[0054] Provided herein, in some aspects, is an antibody that specifically binds trypsin 1 and / or trypsin 2, wherein the antibody comprises a heavy chain variable domain (VH) comprising a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDRl), a HC CDR2, and a HC CDR3, wherein the HC CDR3 comprises 16-22 amino acids residues forming a loop that fits into an active site of trypsin 1 and / or trypsin 2.BRIEF DESCRIPTION OF THE DRAWINGS

[0055] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate certain embodiments, and together with the written description, serve to provide non-limiting examples of certain aspects of the compositions and methods disclosed herein.

[0056] FIG. 1 shows Biacore competition assays comparing binding of three anti-trypsin antibodies (L2-Ab3, L4-Ab3, and L5-Ab2), Ulinastatin (a naturally occurring pan-serine protease inhibitor), Leupeptin (a tripeptide pan-protease inhibitor), and phenylmethanesulfonyl fluoride (PMSF; a small molecule pan-protease inhibitor) to PRSS1. The three anti-trypsin antibodies bind the same active site epitope on PRSS1 as Ulinastatin, Leupeptin and PMSF, pan-protease small molecule inhibitors. Binding is shown as relative response (RU) over time (seconds).

[0057] FIGs. 2A-2G show assessment of binding specificity of several anti-trypsin antibodies: Ll-Abl, Ll-Ab2, L2-Abl, L2-Ab2, L2-Ab3. L2-Ab4, L3-Abl, L3-Ab2, L4-Abl. L4-Ab2, L4-Ab7, L4-Ab6, L4-Ab3, L4-Ab4, L4-Ab5, L5-Abl, and L5-Ab2. Each antibody wasassessed for inhibition of proteolytic activity of proteases closely related to PRSS1 and PRSS2. Antibodies were screened at a single concentration of 10μg / ml and data was normalized to a negative control IgG. FIG.2A shows effects on KLK5 protease activity by each anti-trypsin antibodies. FIG.2B shows effects on inhibition of chymotrypsin by each anti-trypsin antibody.FIG. 2C shows effects on inhibition of Factor Xa by each anti-trypsin antibody. FIG.2D shows effects on inhibition of Cathepsin G by each anti-trypsin antibody. FIG.2E shows effects on inhibition of Cathepsin B by each anti-trypsin antibody. FIG. 2F shows effects on inhibition of Pancreatic Elastase by each anti-trypsin antibody. FIG.2G shows effects on inhibition of Plasmin by each anti-trypsin antibody.

[0058] FIGs. 3A-3B show characterization of cleavage of anti-trypsin antibody by human Trypsin 1. FIG.3A shows results of a denaturing protein gel in which anti-trypsin antibodies (L4-Ab3, L5-Ab2, and L2-Ab5) or control IgG were incubated with active human Trypsin 1 (hTrypsinl), a catalytically inactive hTrypsinl variant, hTrypsinl StoA, or buffer for 16 hours at 37 °C. FIG. 3B shows mass spectrometry analysis of resulting complexes from the experiment in FIG. 3A. An exemplary H3 of L4-Ab3 is shown (ARGDEVVGKRTYYIGMDV (SEQ ID NO: 42)), with K indicating the primary cleavage site (about 66% of all cleavage), and R indicating a secondary cleavage site (about 33% of all cleavage). An exemplary L4-Ab3 shown in FIG. 3 A is apparentlyuncleaved and Vi cleaved after an overnight incubation 37C.

[0059] FIG. 4 shows results of absolute size exclusion chromatography (aSEC) of complexes formed by L4-Ab3, L5-Ab2, or L2-Ab5 with either active human Trypsin 1 (hTrypsinl) or catalytically inactive hTrpysinl (hTrypsinl StoA) after 16-hour incubation.

[0060] FIGs. 5A-5D show binding to and inhibition of trypsin by anti-trypsin antibodies. FIG. 5A shows binding curves (relative response (RU) over Is cycles) for five free anti-trypsin antibodies (L5-Ab2, L4-Ab3, L4-Ab8, L4-Ab9 and L2-Ab5) to immobilized hTrypsinl, hTrypsinl StoA, or control IgG, as determined by a Biacore assay. FIG. 5B shows binding curves for three free anti-trypsin antibodies (L5-Ab2, L4-Ab3, and L2-Ab5) to immobilized hTrypsin2, hTrypsin2 StoA, or control IgG. FIG. 5C shows inhibition of Trypsin activity (normalized to inhibition of control IgGl) by L4-Ab3, L4-Ab8, L4-Ab9, L5-Ab2, L2-Ab5 based on increasing concentrations (nM) of each uncleaved anti-trypsin antibody. Control IgGl (lOOnM) and hTrypsinl (InM) are also shown. FIG.5D shows comparison of integratedhTrypsinl activity following 2-hour incubation with L4-Ab3, L4-Ab8, L4-Ab9, L5-Ab2, L2-Ab5 based on increasing initial concentrations (nM).

[0061] FIGs. 6A-6C show generation and validation of hPRS> SlR122HHOM mice. FIG.6A is a schematic showing insertion of a human PRSS1 gene containing an R122H mutation into a mouse trypsinogen 7 gene (2210010C04RIK) to generate hPRSSlR122HHOM mice. FIG.6B shows mRNA transcripts of hPRSSlR122Hin sera of mice treated with cerulein to induce pancreatitis and sacrificed at 7hrs, 24hrs, or 5 days post first dose, as measured using qPCR. FIG. 6C show's human trypsin protein in mouse pancreas lysate in the same mice, as analyzed using a commercially available ELISA assay (R& D Systems) (FIG. 6C).

[0062] FIGs. 7A-7D show reduction of histological features associated with pancreatitis in hPRSSlR122HHOM mice treated with an anti-trypsin antibody. hPRSSlR122HHOM mice (expressing human Trypsin 1 containing the most common hereditary pancreatitis mutation (R122H)) were generated. Pancreatitis was induced in hPRSSlR122HHOM mice with saline (induction control) or cerulein. Mice were treated with multiple doses of IgGl (treatment control), an anti-trypsin antibody (L4-Ab3) or camostat. Mice were sacrificed on Day 7 and pancreatic tissue was assessed for signatures of pancreatic disease. FIG. 7A shows Edema score (0-5) on Day 7. FIG.7B shows acinar cell necrosis scores (0-5) on Day 7. FIG.7C shows pancreas inflammation scores (0-5) on Day 7. FIG.7D shows representative cross-sections of pancreatic tissue for mice in each condition of FIGs. 6A-6C.

[0063] FIG. 8 shows the predicted three-dimensional structure of an illustrative anti-trypsin 1 / trypsin 2 antibody, L4-Ab3, which is predicted to have a HC CDR 3 loop that fits into the active site of trypsin 1 and trypsin 2.

[0064] FIGs. 9A-9D show in various biomarkers and histological features associated with pancreatitis in cerulein-induced pancreatitis mouse models (hPRSSlR122HHOM) treated with PBS, an IgG control, or an anti-trypsin antibody (20mg / kg or 60mg / kg) 39 hours prior to and 24 hours after pancreatitis induction by cerulein. FIG. 9A shows measures of serum trypsin activity and total trypsin levels at 24 hours post pancreatitis induction. FIG. 9B shows serum amylase levels at 24 hours (left panel), lipase levels at 24 hours (middle panel), and relative pancreas weight per body weight on day 5 (right panel). FIG.9C shows representative histology sections of hematoxylin-eosin-stained pancreas sections for each condition. FIG. 9D show's tissueinflammation, fibrosis, and adipose replacement in pancreas sections for each condition, as scored by a pathologist.

[0065] FIG. 10 shows serum cytokine levels at 24 hours in pancreatitis in cerulein-induced pancreatitis mouse models (hPRSSlR122HHOM).

[0066] FIGs. 11A-11C show the pharmacokinetic profile of an illustrative anti-trypsin 1 / trypsin 2 antibody, L4-Ab3. FIG. HA shows serum L4-Ab3 concentration across 48 hours after a single dose of 10 mg / kg i.v. injection. FIG. 11B shows serum and tissue concentration of L4-Ab3 after 5 days of 30 mg / kg i.v. injection. FIG. 11C shows antibody biodistribution coefficient (ABC) calculated from FIG. 1 IB and a similar experiment using a 60 mg / kg dose.

[0067] FIG. 12 shows representati ve histology sections of formalin-fixed, paraffin-embedded pancreas tissue from hPRSSlR122HHOM mice without cerulein induction, cerulein-induced pancreatitis model hPRSSlR122HHOM mice (CRN) pre-treated with an IgG control (“CRN + Con-IgG”) or with L4-Ab3 (20mg / kg) (“CRN + L4-Ab3”) 39 hours prior to and 24 hours after pancreatitis induction. Tissue is stained with H& E, and stained for caspase-3, Cdllb, F40 / 80, and a-SMA.

[0068] FIGs. 13A-13D show improvements in various biomarkers associated with pancreatitis in cerulein-induced pancreatitis mouse models (hPRSSlR122HHOM) pre-treated 18-hours before pancreatitis induction with PBS, an IgG control, or an anti-trypsin antibody (lOmg / kg or 20mg / kg); or treated with PBS, an IgG control, or an anti-trypsin antibody (lOmg / kg or 20mg / kg) 7 hours after pancreatitis induction. FIG. 13A shows measures of serum trypsin activity at 24 hours post pancreatitis induction. FIG. 13B shows total trypsin levels at 24 hours post pancreatitis induction. FIG. 13C shows serum amylase levels at 24 hours post pancreatitis induction. FIG. 13D shows lipase levels at 24 hours post pancreatitis induction.

[0069] FIGs. 14A-14D show serum cytokine levels at 24 hours in pancreatitis in cerulein- induced pancreatitis mouse models (hPRSSlR122HHOM) pre-treated 18-hours before pancreatitis induction with PBS, an IgG control, or an anti-trypsin antibody (lOmg / kg or 20mg / kg); or treated with PBS, an IgG control, or an anti-trypsin antibody (lOmg / kg or 20mg / kg) 7 hours after pancreatitis induction; cytokines include MCP-1 (FIG. 14A), IL-5 (FIG. 14B), IL-6 (FIG. 14C), and KC / GRO (FIG. 14D),

[0070] FIGs. 15A-15D show improvements in various histological features associated with pancreatitis in cerulein-induced pancreatitis mouse models (hPRSSlR122HHOM) pre-treated 18-hours before pancreatitis induction with PBS, an IgG control, or an anti-trypsin antibody (lOmg / kg or 20mg / kg); or treated with PBS, an IgG control, or an anti-trypsin antibody (20mg / kg) 7 hours after pancreatitis induction. FIG. 15A shows relative pancreas weight per body weight on day 5. FIG. 15B shows tissue inflammation for each treatment condition, as scored by a pathologist. FIG. 15C shows fibrosis for each treatment condition, as scored by a pathologist. FIG. 15D shows a total score for each treatment condition, as scored by a pathologist.DETAILED DESCRIPTION

[0071] As discussed herein, activation of trypsin (e.g., trypsin 1 and trypsin 2) in the pancreas is associated with the development of pancreatitis. Trypsin enzymes are synthesized as trypsinogen, an inactive precursor, in the rough endoplasmic reticulum and transported to the Golgi apparatus for sorting in the pancreas. Trypsinogen is co-synthesized and packed with a pancreatic secretory trypsin inhibitor (PSTI) that inhibits its premature activation. These zymogen granules are released into the lumen of pancreatic duct, which carries the digestive enzymes into the duodenum. Once in duodenum, enteropeptidase activates trypsinogen into active trypsin. Trypsin 1 is the most abundant trypsin enzyme secreted by the pancreas followed by trypsin 2. Accordingly, the present disclosure, at least in part, is based on the development of dual inhibitor antibodies and variants thereof targeting trypsin 1 and trypsin 2. These dual inhibitor antibodies target trypsin 1 and trypsin 2 via a common distinct antigen-specific binding site. Such dual inhibitor antibodies have high binding affinity and specificity to trypsin 1 and trypsin 2 (also referred to as anti-trypsin 1 / trypsin 2 antibodies in the present disclosure). Also provided are methods of using the anti- trypsin 1 / trypsin 2 antibodies and their variants in research, diagnostic / detection, and therapeutic applications.I. Definitions

[0072] Administering: As used herein, the terms “administering” or “administration” mean to provide an antibody or a composition thereof to a subject in a manner that is physiologically and / or pharmacologically useful (e.g., to treat a condition in the subject).

[0073] Affinity Matured Antibody: The term “Affinity Matured Antibody” is used herein to refer to an antibody with one or more alterations in one or more CDRs, which result in animprovement in the affinity (e g.. KD, kd or ka) of the antibody for a target antigen compared to a parent antibody, which does not possess the alteration(s). Exemplary affinity matured antibodies may have nanomolar or even picomolar affinities for the target antigen in some embodiments. A variety of procedures for producing affinity matured antibodies are available, including the screening of a combinatory antibody library that has been prepared using bio-display. For example, Marks et al., BioTechnology, 10: 779-783 (1992) describes affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and / or framework residues is described by Barbas et al., Proc. Nat. Acad. Sci. US A, 91: 3809-3813 (1994); Schier et al., Gene, 169: 147-155 (1995); Yelton et al., J. Immunol., 155: 1994-2004 (1995); Jackson et al., J. Immunol.. 154(7): 3310-3319 (1995); and Hawkins et al, J. Mol. Biol., 226: 889-896 (1992). Selective mutation at selective mutagenesis positions and at contact or hypermutation positions with an activity-enhancing amino acid residue is described in U. S. Pat. No. 6,914,128 Bl.

[0074] Antibody: As used herein, the term “antibody” refers to a polypeptide that comprises at least one immunoglobulin variable domain, which comprises at least one distinct antigenspecific binding site, or a portion of an immunoglobulin variable domain (such as a paratope or portion thereof) that comprises at least one distinct antigen-specific binding site. In some embodiments, an antibody is a full-length antibody. In some embodiments, an antibody is a chimeric antibody. In some embodiments, an antibody is a humanized antibody. However, in some embodiments, an antibody is a Fab fragment, a F(ab’)2 fragment, a Fv fragment or a scFv fragment. In some embodiments, an antibody is a multi-specific antibody (e.g., a bispecific antibody), hi some embodiments, an antibody is a nanobody derived from a camelid antibody or a nanobody derived from shark antibody. In some embodiments, an antibody is a diabody. In some embodiments, an antibody comprises a framework having a human germline sequence, hi another embodiment, an antibody comprises a heavy chain constant domain selected from the group consisting of IgG, IgGl, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgAl, IgA2, IgD, IgM, and IgE constant domains. In some embodiments, an antibody comprises a heavy (H) chain variable region (abbreviated herein as VH), and / or a light (L) chain variable region (abbreviated herein as VL). In some embodiments, an antibody comprises a constant domain, e.g., an Fc region. An immunoglobulin constant domain refers to a heavy or light chain constant domain. Human IgG heavy chain and light chain constant domain amino acid sequences andtheir functional variations are known. With respect to the heavy chain, in some embodiments, the heavy chain of an antibody described herein can be an alpha (a), delta (A), epsilon (e), gamma (y) or mu (p) heavy chain. In some embodiments, the heavy chain of an antibody described herein can comprise a human alpha (a), delta (A), epsilon (e), gamma (y) or mu (p) heavy chain. In a particular embodiment, an antibody described herein comprises a human gamma 1 CH1, CH2, and / or CH3 domain. In some embodiments, the amino acid sequence of heavy chain comprises the amino acid sequence of a human gamma (y) heavy chain constant region, such as any known in the art. Non-limiting examples of human constant region sequences have been described in the art, e.g., see U. S. Pat. No. 5,693,780 and Kabat E A et al., (1991) supra. In some embodiments, the heavy chain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the heavy chain constant regions provided herein. In some embodiments, an antibody is modified, e.g., modified via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, an antibody is a glycosylated antibody, which is conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecule are conjugated to the antibody via N -glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecule are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecule is a branched oligosaccharide or a branched glycan. In some embodiments, the one or more sugar or carbohydrate molecule includes a mannose unit, a glucose unit, an N-acetylglucosamine unit, or a phospholipid unit. In some embodiments, an antibody is a construct that comprises a polypeptide comprising one or more antigen binding fragments of the disclosure linked to a linker polypeptide or an immunoglobulin constant domain. Linker polypeptides comprise two or more amino acid residues joined by peptide bonds and are used to link one or more antigen binding portions. Examples of linker polypeptides have been reported (see e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, R. J., et al. (1994) Structure 2:1121-1123). Still further, an antibody may be part of a larger immunoadhesion molecule, formed by covalent or noncovalent association of the antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to make a tetrameric scFv molecule (Kipriyanov, S. M., et al. (1995)Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue, a marker peptide and a C -terminal polyhistidine tag to make bivalent and biotinylated scFv molecules (Kipriyanov, S. M., et al. (1994) Mol. Immunol. 31:1047-1058).

[0075] Approximately: As used herein, the term “approximately” or “about,” as applied to one or more values of interest, refers to a value that is similar to a stated reference value. In certain embodiments, the term “approximately” or “about” refers to a range of values that fall within 15%, 14%, 13%. 12%, 11%, 10%, 9%, 8%, 7%. 6%, 5%, 4%, 3%, 2%, 1%, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100% of a possible value).

[0076] Bispecific Antibody: As used herein, the term “bispecific antibody” refers to an antibody that comprises two distinct antigen-specific binding sites or two linked (covalently or non-covalently) antibodies that, combined, comprise two distinct antigen -specific binding sites. Non-limiting examples of bispecific antibody formats or architectures are provided in Labrijn, AF, et al., Bispecific antibodies: a mechanistic review of the pipeline. Nature Reviews Drug Discovery volume 18, pages 585-608 (2019) and Brinkmann U and Kontermann EE, The making of bispecific antibodies, MAbs. 2017 Feb / Mar;9(2): 182-212, the entire contents of each of which are incorporated herein by reference in their entireties.

[0077] CDR: As used herein, the term " CDR" refers to the complementarity determining region within antibody variable sequences. A typical antibody molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), which are usually involved in antigen binding. The VH and VL regions can be further subdivided into regions of hypervariability, also known as “complementarity determining regions” (“CDR”), interspersed with regions that are more conserved, which are known as “framework regions” (“FR”). Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy -terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework region and CDRs can be precisely identified using methodology known in the art, for example, by the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the contact definition, all of which are well known in the art. See, e.g., Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U. S.Department of Health and Human Services, NIH Publication No. 91-3242; IMGT®, theinternational ImMunoGeneTics information system®, Lefranc, M.-P. et al., Nucleic Acids Res., 27:209-212 (1999); Ruiz, M. et al., Nucleic Acids Res., 28:219-221 (2000); Lefranc, M.-P., Nucleic Acids Res., 29:207-209 (2001); Lefranc, M.-P. Nucleic Acids Res., 31:307-310 (2003); Lefranc, M.-P. et al., In Silico Biol., 5, 0006 (2004) Epub. 5:45-60 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 33: D593-597 (2005); Lefranc, M.-P. et al., Nucleic Acids Res., 37: D1006-1012 (2009); Lefranc, M.-P. et al., Nucleic Acids Res., 43: D413-422 (2015); Chothia et al., (1989) Nature 342:877; Chothia, C. et al. (1987) J. Mol. Biol. 196:901-917, Al-lazikani et al (1997) J. Molec. Biol. 273:927-948; and Almagro, J. Mol. Recognit. 17:132-143 (2004). See also hgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, a CDR may refer to the CDR defined by any method known in the art. Two antibodies having the same CDR means that the two antibodies ha ve the same amino acid sequence of that CDR as determined by the same method, for example, the IMGT definition.

[0078] In certain embodiments, there are three CDRs in each of the variable regions of a heavy chain and a light chain, which are designated CDR1, CDR2 and CDR3, for each of the variable regions. The term " CDR set" as used herein refers to a group of three CDRs that occur in a single variable region capable of binding the antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system described by Kabat (Rabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Sub-portions of CDRs may be designated as LI, L2 and L3 or Hl, H2 and H3 where the " L" and the " H" designates the light chain and the heavy chains regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan (FASEB J. 9:133-139 (1995)) and MacCallum (J Mol Biol 262(5):732-45 (1996)). Still other CDR boundary definitions may not strictly follow one of the above systems, but will nonetheless overlap with the Kabat CDRs, although they may be shortened or lengthened in light of prediction or experimental findings that particular residues or groups of residues or even entire CDRs do not significantly impact antigen binding. The methods used herein may utilize CDRsdefined according to any of these systems, although preferred embodiments use Kabat or Chothia defined CDRs.

[0079] In certain embodiments, the CDRs of an antibody may have different amino acid sequences when different definition systems are used (e.g., the IMGT definition, the Kabat definition, the Chothia definition, or any other known definition). A definition system annotates each amino acid in a given antibody sequence (e.g., VH or VL sequence) with a number, and numbers corresponding to the heavy chain and light chain CDRs are provided in Table 2. One skilled in the art is able to derive the CDR sequences using the different numbering systems for the anti-trypsin 1 / trypsin 2 antibodies provided in Tables la and lb.Table 2. CDR DefinitionsIMGT1Kabat2Chothia3HC CDR1 27-38 31-35 26-32HC CDR2 56-65 50-65 53-55HC CDR3 105-116 / 117 95-102 96-101LC CDR1 27-38 24-34 26-32LC CDR2 56-65 50-56 50-52LC CDR3 105-116 / 117 89-97 91-961IMGT®, the international ImMunoGeneTics information system®, imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res.. 27:209-212 (1999)2Kabat et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U. S.Department of Health and Human Services, NIH Publication No. 91-32423Chothia et al., J. Mol. Biol. 196:901-917 (1987))

[0080] CDR-grafted antibody: As used herein, the term " CDR-grafted antibody" refers to antibodies which comprise heavy and light chain variable region sequences from one species but in which the sequences of one or more of the CDR regions of VH and / or VL are replaced with CDR sequences of another species, such as antibodies having murine heavy and light chain variable regions in which one or more of the murine CDRs (e.g., CDR3) has been replaced with human CDR sequences.

[0081] Chimeric antibody: As used herein, the term "chimeric antibody" refers to antibodies which comprise heavy and light chain variable region sequences from one species and constantregion sequences from another species, such as antibodies having murine heavy and light chain variable regions linked to human constant regions.

[0082] Complementary: As used herein, the term “complementary” refers to the capacity for precise pairing between two nucleotides or two sets of nucleotides. In particular, complementary is a term that characterizes an extent of hydrogen bond pairing that brings about binding between two nucleotides or two sets of nucleotides. For example, if a base at one position of an oligonucleotide is capable of hydrogen bonding with a base at the corresponding position of a target nucleic acid (e.g., an mRNA), then the bases are considered to be complementary to each other at that position. Base pairings may include both canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., Wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for complementary base pairings, adenosine-type bases (A) are complementary to thymidine-type bases (T) or uracil-type bases (U), that cytosine-type bases (C) are complementary to guanosine-type bases (G), and that universal bases such as 3-nitropyrrole or 5-nitroindole can hybridize to and are considered complementary to any A, C, U, orT. Inosine (I) has also been considered in the art to be a universal base and is considered complementary to any A, C, U or T.

[0083] Conservative amino acid substitution: As used herein, a “conservative amino acid substitution” refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the amino acid substitution is made. Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references which compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et al., eds., Fourth Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F. M. Ausubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative substitutions of amino acids include substitutions made amongst amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q. N; and (g) E, D.

[0084] Cross-reactive: As used herein, the term “cross-reactive,” refers to a property of the agent being capable of specifically binding to more than one antigen of a similar type or class (e.g., antigens of multiple homologs, paralogs, or orthologs) with similar affinity or avidity. For example, in some embodiments, an antibody that is cross-reactive against human and non-human primate antigens of a similar type or class (e.g., a human trypsin 1 and non-human primatetrypsin 1, a human trypsin 2 and non-human primate trypsin 2) is capable of binding to the human antigen and non-human primate antigens with a similar affinity or avidity. In some embodiments, an antibody is cross-reactive against a human antigen and a rodent antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a rodent antigen and a non-human primate antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a human antigen, a non-human primate antigen, and a rodent antigen of a similar type or class.

[0085] Dual Inhibitor Antibody: As used herein, the term “dual inhibitor antibody” refers to an antibody that targets at least two (e.g., two, three) different antigens via a common distinct antigen -specific binding site and inhibits activity of those antigens. In some embodiments, a dual inhibitor antibody targets at least two different proteins (e.g., expressed from two different genes (e.g., endogenous genes, e.g., homologues, paralogues) via a common distinct antigen-specific binding site and inhibits activity of the at least two different proteins (e.g., enzymes, such as proteases). In some embodiments, a dual inhibitor antibody targets at least two different proteases (e.g., expressed by two different endogenous genes, e.g., trypsin 1 and trypsin 2) via a common distinct antigen-specific binding site and inhibits activity of the at least two different proteases. In some embodiments, the common distinct antigen-specific binding site binds to a similar (e.g., homologous) domain shared between or among the at least two different antigens. For example, in some embodiments, the common distinct antigen-specific binding site binds to a similar (e.g., homologous) catalytic domain or substrate binding site shared between or among the at least two different enzymes, e.g., proteases. In some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody comprises amino acids of one or more complementarity determining regions of the antibody. In some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody is within a heavy chain variable region and / or a light chain variable region of the antibody, hi some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody comprises one or more complementarity determining regions of a heavy chain variable region and / or a light chain variable region of the antibody. In some embodiments, the common distinct antigen-specific binding site of a dual inhibitor antibody comprises HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 of a heavy chain variable region and a light chain variable region ofthe antibody. In some embodiments, a dual inhibitor antibody specifically binds to two different proteins expressed from two different genes (e.g., PRSS1 gene and PRSS2 gene).

[0086] Effective Amount: As used herein, “an effective amount” refers to the amount of each active agent (e.g., anti- trypsin 1 / trypsin 2 antibody) required to confer a desired effect (e.g., a therapeutic effect on the subject), either alone or in combination with one or more other active agents. In some embodiments, the therapeutic effect is reduced trypsin 1 and / or trypsin 2 activity and / or alleviated disease (e.g., pancreatitis) or related symptoms, e.g., improved barrier function.

[0087] Framework: As used herein, the term "framework" or "framework sequence" refers to the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined by different systems, the meaning of a framework sequence is subject to correspondingly different interpretations. The six CDRs (CDR-L1, CDR-L2, and CDR-L3 of light chain and CDR-H1, CDR-H2, and CDR-H3 of heavy chain) also divide the framework regions on the light chain and the heavy chain into four sub-regions (FR1, FR2, FR3 and FR4) on each chain, in which CDR1 is positioned between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without specifying the particular sub-regions as FR1, FR2, FR3 or FR4, a framework region, as referred by others, represents the combined FRs within the variable region of a single, naturally occurring immunoglobulin chain. As used herein, a FR represents one of the four sub-regions, and FRs represents two or more of the four sub-regions constituting a framework region. Human heavy chain and light chain acceptor sequences are known in the ait. In one embodiment, the acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0088] Human antibody: The term "human antibody", as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site¬ specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular CDR3. However, the term "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0089] Humanized antibody: As used herein, the term "humanized antibody" refers to antibodies which comprise heavy and light chain variable region sequences from a non-humanspecies (e.g., a mouse) but in which at least a portion of the VH and / or VL sequence has been altered to be more "human-like", i.e., more similar to human germline variable sequences. One type of humanized antibody is a CDR-grafted antibody, in which human CDR sequences are introduced into non-human VH and VL sequences to replace the corresponding nonhuman CDR sequences. In one embodiment, humanized antibodies are provided. Such antibodies may be generated by obtaining murine monoclonal antibodies using traditional hybridoma technology followed by humanization using in vitro genetic engineering, such as those disclosed in Kasaian et al PCT publication No. WO 2005 / 123126 A2.

[0090] Humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, the humanized antibody may comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Antibodies may have Fc regions modified as described in WO 99 / 58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, six) which are altered with respect to the original antibody, which are also termed one or more CDRs derived from one or more CDRs from the original antibody. Humanized antibodies may also involve affinity maturation.

[0091] In some embodiments, humanization is achieved by grafting the CDRs (e.g., as shown in Tables la, or lb) into the human variable domains (e.g., IGKVl-NLl*01 and IGHVl-3*01 human variable domain). In some embodiments, an antibody of the present disclosure is a humanized variant comprising one or more amino acid substitutions (e.g., in the VH framework region) as compared with any one of the VHs listed in Tables la, or lb and / or one or more aminoacid substitutions (e.g., in the VL framework region) as compared with any one of the VLs listed in Tables la, or lb.

[0092] Isolated antibody: An "isolated antibody", as used herein, is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated dual inhibitor antibody that specifically binds trypsin 1 and trypsin 2 is substantially free of antibodies that specifically bind antigens other than trypsin 1 and trypsin 2). An isolated antibody may, however, have cross-reactivity to other antigens, in some embodiments.Moreover, an isolated antibody may be substantially free of other cellular material and / or chemicals.

[0093] Kabat numbering: As used herein, the terms " Kabat numbering", " Kabat definitions”, and " Kabat labeling" are used interchangeably herein. These terms, which are recognized in the art, refer to a system of numbering amino acid residues which are more variable (i.e. hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody, or an antigen binding portion thereof (Kabat et al. (1971) Ann. NY Acad, Sei. 190:382-391 and, Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U. S. Department of Health and Human Services, NIH Publication No. 91-3242). For the heavy chain variable region, the hypervariable region ranges from amino acid positions 31 to 35 for CDR1, amino acid positions 50 to 65 for CDR2, and amino acid positions 95 to 102 for CDR3. For the light chain variable region, the hypervariable region ranges from amino acid positions 24 to 34 for CDR1, amino acid positions 50 to 56 for CDR2, and amino acid positions 89 to 97 for CDR3.

[0094] Multi-Specific Antibody: As used herein, the term “multi-specific antibody” refers to an antibody that comprises at least two distinct antigen-specific binding sites or at least two linked (covalently or non-covalently) antibodies that, combined, comprise at least two distinct antigen-specific binding sites. In some embodiments, a multi-specific antibody is a bispecific antibody. Non-limiting examples of multi-specific specific antibody formats or architectures are provided in Sawant MS, et al., Toward Drug-Like Multispecific Antibodies by Design, Int J Mol Sci. 2020 Oct 12;21(20):7496; Klein C, et al., The use of CrossMAb technology for the generation of bi- and multispecific antibodies, MAbs 2016 Aug-Sep;8(6): 1010-20; and Brinkmann U and Kontermann EE, The making of bispecific antibodies, MAbs. 2017Feb / Mar;9(2): 182-212, the entire contents of each of which are incorporated herein by reference in their entireties.

[0095] Recombinant antibody: As used herein, the term "recombinant antibody" is intended to include all antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described in more details in this disclosure), including, for example, antibodies isolated from a recombinant, combinatorial human antibody library (Hoogenboom H. R., (1997) TIB Tech. 15:62-70; Azzazy H., and Highsmith W. E., (2002) Clin. Biochem. 35:425-445; Gavilondo J. V., and Larrick J. W. (2002) BioTechniques 29:128-145; Hoogenboom H., and Chames P. (2000) Immunology Today 21:371-378), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L. D., et al. (1992) Nucl. Acids Res. 20:6287-6295; Kellermann S-A., and Green L. L. (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al (2000) Immunology Today 21:364-370) or antibodies prepared, expressed, created or isolated by any other means that involves splicing of human immunoglobulin gene sequences to other DNA sequences. In some embodiments, recombinant human antibodies are provided herein. In certain embodiments, such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis) and thus the amino acid sequences of the VH and VL regions of the recombinant antibodies are sequences that, while derived from and related to human germline VH and VL sequences, may not naturally exist within the human antibody germline repertoire in vivo. One embodiment of the disclosure provides fully human antibodies, e.g., human antibody VH domain and a human antibody VL domain, which can be generated using appropriate techniques, such as, but not limited to, using human Ig phage libraries such as those disclosed in Jermutus et al., PCT publication No. WO 2005 / 007699 A2.

[0096] Selective: As used herein, the term “selective” or “selectively” refers to the ability of a molecule to produce an effect (e.g., inhibit, antagonize, agonize, etc) in relation to its target molecule compared to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that this molecule is capable of inhibiting its target molecule with a degree that is distinguishable from a reference molecule in an inhibition assay or other inhibitorycontext. For example, with respect to an inhibitor, the term, “selectively inhibits,” refers to the ability of the inhibitor to inhibit its target molecule with a degree that is distinguishable from a reference molecule that is not substantially inhibited in an inhibition assay, e g., to an extent that permit selective inhibition of the target molecule, as described herein. Once the reaction is terminated, the signal produced by inhibiting the target molecule can be measured. The half maximal inhibitor concentration for the target molecule and the reference molecule can be calculated.

[0097] Specifically binds: As used herein, the term “specifically binds” refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that enables the molecule to be used to distinguish the binding partner from an appropriate control in a binding assay or other binding context. With respect to an antibody, the term, “specifically binds,” refers to the ability of the antibody to bind to a specific antigen with a degree of affinity or avidity, compared with an appropriate reference antigen or antigens, that enables the antibody to be used to distinguish the specific antigen from others, as described herein. In some embodiments, an antibody specifically binds to a target if the antibody has a KD for binding the target of at least about IO’4M, 10’5M, IO’6M, IO’7M, IO’8M, 10’9M, IO’10M, l()’nM, IO’12M, IO’13M, or less. In some embodiments, an antibody specifically binds trypsin 1 or trypsin 2.

[0098] Subject: As used herein, the term “subject” refers to a mammal. In some embodiments, a subject is a non-human primate, or a rodent. In some embodiments, a subject is a human. In some embodiments, a subject is a patient, e.g., a human patient that has or is suspected of having a disease.

[0099] Treatment: As used herein, the term “treating” or “treatment” refers to the application or administration of a composition including one or more active agents (e.g., anti-trypsin 1 / trypsin 2 antibodies) to a subject, who has a target disease or disorder, a symptom of the disease / disorder, or a predisposition toward the disease / disorder, with the purpose to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve, or affect the disorder, the symptom of the disease, or the predisposition toward the disease or disorder. Alleviating a target disease / disorder includes delaying or preventing the development or progression of the disease, or reducing disease severity.II. Dual Inhibitor Antibodies Targeting Trypsin 1 and Trypsin 2[000100] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody is an antibody specific for both trypsin 1 and trypsin 2 via a common, specific antigen binding site. Provided herein, in some aspects, are antibodies that bind to trypsin- 1 (e.g., human trypsin 1, or non-human primate trypsin 1) and trypsin 2 (e.g., human trypsin 2, or non-human primate trypsin 2) with high specificity and affinity via a common antigen binding site. In some embodiments, the anti-trypsin 1 / trypsin 2 antibody described herein specifically binds to an epitope of trypsin 1 that is exposed or becomes exposed to an antibody, and an epitope of trypsin 2 that is exposed or becomes exposed to an antibody. In some embodiments, anti- Trypsin 1 / trypsin 2 antibodies provided herein bind specifically to trypsin 1 from human, non-human primates, etc. In some embodiments, anti-trypsin 1 antibodies provided herein specifically bind to human trypsin 1. In some embodiments, anti-trypsin 1 antibodies provided herein specifically bind to mouse trypsin 1.[000101] Trypsins are serine proteases produced in the pancreas and have important roles in the digestive systems of vertebrates (e.g., digestion of fats and proteins). Stimulation of the pancreas, e.g., by cholecystokinin, results in excretion of one or more of three isoforms of trypsinogens, the inactive forms of trypsins (sometimes referred to as the proforms or pro-forms of trypsins), by pancreatic acinar cells. In humans, these trypsinogens include trypsinogen- 1 (cationic trypsinogen), trypsinogen-2 (anionic trypsinogen), and trypsinogen-3 (inhibitor-resistant mesotrypsinogen). Once in the small intestine, trypsinogens are activated by enzymes (e.g., by enterokinase or active trypsins) to form catalytically active trypsins, which can, in turn, activate more trypsinogens and other pancreatic zymogens (e.g., chymotrypsinogen, procarboxypeptidase, and proelastase). Trypsin is eventually inactivated in the circulatory system, e.g., when bound to α1-antitrypsin (AAT) as part of a trypsin-AAT complex. Due in part to its ability to regulate activation of other digestive enzymes, trypsins play important roles in digestion and pancreatic function. Indeed, dysregulation (e.g., overactivation, overexpression) of some trypsin subtypes (e.g., trypsin 1, trypsin 2) is associated with pancreatic disease.Accordingly, certain compositions and methods described herein may be useful for, in some aspects, modulating activity (e.g., inhibiting activity) of one or more trypsins.[000102] Trypsin 1, also known as cationic trypsinogen, is a protease encoded by the PRSS1 gene on chromosome 7. Trypsin- 1 is the active form of the main isoform of trypsinogen secreted by pancreas. The PRSS1 gene encodes a trypsinogen, which is a member of the trypsin family ofserine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Certain mutations in the PRSS1 gene are autosome dominant mutations that lead to overactivation of trypsin 1, which is associated with hereditary pancreatitis. Further, the activity of trypsin 1 (e.g., with or without PRSS1 mutation) has been associated with the occurrence of pancreatitis (see, e.g., Gui et al., Trypsin activity governs increased susceptibility to pancreatitis in mice expressing human PRSS1R122H, J Clin Invest. 2020;130(1):189–202; Sendler et al., The Complex Role of Trypsin in Pancreatitis, Gastroenterology, EDITORIAL VOLUME 158, ISSUE 4, P822-826, MARCH 2020; Logsdon, Phosphatidylinositol 3-kinase and trypsin activation in pancreatitis, J Clin Invest. 2001 Nov 1; 108(9): 1267-1268). Indeed, certain mutations in the PRSS1 gene are autosome dominant mutations (e.g., R122H) that lead to overactivation of trypsin 1, which is associated with hereditary pancreatitis, as described in the section entitled “(a) Treatment of Hereditary Pancreatitis (HP)”.[000103] Trypsin 2, also known as anionic trypsinogen, is a protease encoded by the PRSS2 gene on chromosome 7. Trypsin 2 is the second most abundant trypsin secreted by the pancreas. Trypsin 2 has also been shown to be associated with pancreatitis (see, e.g., Dixit, Role of trypsinogen activation in genesis of pancreatitis, Pancreapedia: Exocrine Pancreas Knowledge Base, DOI: 10.3998 / panc.2016.25; Kemppainen et al., Increased serum trypsinogen 2 and trypsin 2-al -antitrypsin complex values identify endoscopic retrograde cholangiopancreatography induced pancreatitis with high accuracy, Gut 1997;41:690-695; Andersen et al., The ratio of trypsin-2-alpha(l)-antitrypsin to trypsinogen- 1 discriminates biliary and alcohol-induced acute pancreatitis, Clinical Chemistry, 01 Feb 2001, 47(2):231-236; Yu et al., Altered Gene Expression in Caerulein-Stimulated Pancreatic Acinar Cells: Pathologic Mechanism of Acute Pancreatitis, Korean J Physiol Pharmacol 2009; 13 (6): 409-416).[000104] hi some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein specifically binds to an epitope on human trypsin 1. Exemplary amino acid sequences of human trypsin 1 are set forth in NCBI Accession Numbers NP_002760.1, and UniProt Accession Numbers: P07477, or P00760, the entire sequences of which are incorporated herein by reference.[000105] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein specifically binds to an epitope on human trypsin 1. In some embodiments, the serine in thecatalytic domain of human trypsin 1 is mutated to alanine to raise the antibodies described herein. An exemplary amino acid sequence of human trypsin 1 with serine to alanine mutation is set forth in SEQ ID NO: 103 (including a His tag at C terminus):IVGGYNCEENSVP YQVSLNSGYHFCGGSLINEQWWSAGHCYKSRIQVRLGEHNIEVLE GNEQFINAAKIIRHPQYDRKTLNNDIMLIKLSSRAVINARVSTISLPTAPPATGTKCLI SGWGNTASSGADYPDELQCLDAPVLSQAKCEASYPGK1TSNMFCVGFLEGGKDSCQGDA GGPWCNGQLQGVVSWGDGCAQKNKPGVYTKVYNYVKWIKNTIAANSHHHHHH (SEQ ID NO: 103)[000106] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein specifically binds to an epitope on human trypsin 2. Exemplary amino acid sequences of human trypsin 2 are set forth in NCBI Accession Numbers NP_001290343.1, or NP_002761.1, and UniProt Accession Numbers: P07478, the entire sequences of which are incorporated herein by reference. In some embodiments,[000107] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein specifically binds to an epitope on human trypsin 2. In some embodiments, the serine in the catalytic domain of human trypsin 2 is mutated to alanine to raise the antibodies described herein. An exemplary amino acid sequence of human trypsin 2 with serine to alanine mutation is set forth in SEQ ID NO: 104 (including a His tag at C terminus):IVGGYICEENSVPYQVSLNSGYHFCGGSLISEQWWSAGHCYKSRIQVRLGEHNIEVLE GNEQFINAAKIIRHPKYNSRTLDNDILLIKLSSPAVINSRVSAISLPTAPPAAGTESLI SGWGNTLSSGADYPDELQCLDAPVLSQAECEASYPGK1TNNMFCVGFLEGGKDSCQGDA GGPWSNGELQGIVSWGYGCAQKNRPGVYTKVYNYVDWIKDTI ANSHHHHHH (SEQ ID NO: 104)[000108] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein specifically binds to an epitope on trypsin 1 (e.g., the catalytic domain / pocket of human trypsin 1 or non-human primate trypsin 1) and an epitope on trypsin 2 (e.g., the catalytic domain / pocket of human trypsin 2 or non-human primate trypsin 2). In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein binds to the active form of trypsin- 1 and trypsin 2. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein prevents trypsin 1 (e.g., the catalytic domain / pocket of human trypsin 1 or non-human primate trypsin 1) and trypsin 2 (e.g., the catalytic domain / pocket of human trypsin 2 or non-human primate trypsin 2) from cleaving its substrates. Trypsin-mediated catalysis of peptide substrates occurs at the catalytic domain / pocket of trypsin, comprising a catalytic triad consisting of Aspl02, His 57, and Serl95.When the substrate is present, the catalytic triad forms a pocket in which the three residues are positioned for a nucleophilic attack on the lysine or arginine of the substrate, thereby cleaving the substrate. Without wishing to be bound by theory, it is believed that by blocking this active site (e.g., by binding with an anti-trypsin 1 / trypsin 2 antibody), proteolytic activity of trypsin can be inhibited. However, because trypsins (e.g., trypsin 1 and trypsin 2) are proteases, targeting of trypsin at the active site can lead to cleavage of an anti-trypsin 1 / trypsin 2 antibody described herein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein does not bind to inactive form (i.e., the proform) of trypsin 1 and trypsin 2. In some embodiments, the HC CDR3 loop of an anti-trypsin 1 / trypsin 2 antibody described herein inserts into the catalytic domain of the active form of trypsin 1 and trypsin 2, thereby inhibiting the protease activity of trypsin 1 and trypsin 2. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein is cleaved by trypsin 1 and / or trypsin 2 but a fragment after cleavage remains bound to the active site of trypsin 1 and trypsin 2 and continues to inhibit the protease activity of trypsin 1 and trypsin 2. In some embodiments, HC CDR3 of an anti-trypsin 1 / trypsin 2 antibody described herein is cleaved by trypsin 1 and / or trypsin 2 but a fragment after cleavage remains bound to the active site of trypsin 1 and trypsin 2 and continues to inhibit the protease activity of trypsin 1 and trypsin 2. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein competes with Ulinastatin, Leupeptin and PMSF for binding to trypsin 1 and trypsin 2.[000109] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein inhibits protease activity of trypsin 1. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein inhibits protease activity of trypsin 2. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein inhibits protease activity of both trypsin 1 and trypsin 2. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein inhibits trypsin 1-mediated cleavage of peptide linkages involving the carboxyl group of lysine or arginine of a protein (e.g., peptide). In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein inhibits trypsin 1 -mediated cleavage of peptide linkages involving the carboxyl group of lysine or arginine of a protein with an IC50 of less than 2nM, less than 1.9nM, less than 1.8nM, less than 1.7nM, less than 1.6nM, less than 1.5nM, less than 1.4nM, less than 1.3nM, less than 1.2nM, less than l.lnM, less than InM, less than 0.9 nM. less than 0.8 nM, less than 0.7 nM, less than 0.6 nM, less than 0.5 nM, less than 0.4 nM, less than 0.3 nM, less than 0.2 nM, or less than 0.1 nM. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody described herein inhibitstrypsin 2-mediated cleavage of peptide linkages involving the carboxyl group of lysine or arginine of a protein with an IC50 of less than 2nM, less than 1.9nM, less than 1.8nM, less than 1.7nM, less than 1.6nM, less than 1.5nM, less than 1.4nM, less than 1.3nM, less than 1.2nM, less than 1. InM, less than InM, less than 0.9 nM, less than 0.8 nM, less than 0.7 nM, less than 0.6 nM, less than 0.5 nM, less than 0.4 nM, less than 0.3 nM, less than 0.2 nM, or less than 0.1 nM.[000110] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody described herein bind to a fragment of trypsin 1 (e.g., the catalytic domain / pocket of human trypsin 1 or non-human primate trypsin 1 ) and a fragment of trypsin 2 (e.g., the catalytic domain / pocket of human trypsin 2 or non-human primate trypsin 2). The fragment of trypsin 1 and / or trypsin 2 (e.g., human or non-human primate) may be between about 5 and about 425 amino acids, between about 10 and about 400 amino acids, between about 50 and about 350 amino acids, between about 100 and about 300 amino acids, between about 150 and about 250 amino acids, between about 200 and about 300 amino acids, between about 75 and about 150 amino acids, between about 25 and about 100 amino acids, between about 10 and about 30 amino acids in length. Not wishing to be bound to any particular theory, and in some embodiments, a heavy chain (HC) complementaritydetermining region 3 (CDR3) of any one of the anti-trypsin 1 / trypsin 2 antibodies described herein inhibits trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) by binding to the catalytic domain / pocket of trypsin 1 and trypsin 2 respectively.[000111] In some embodiments, antibodies described herein are optimized versions (e.g., affinity matured) of the parental antibody. In some embodiments, an antibody described herein specifically binds trypsin 1 (e.g., a human or non-human primate trypsin 1) and trypsin 2 (e.g., a human or non-human primate trypsin 2) with binding affinity (e.g., as indicated by KD) of at least about 10 M, i 04M, 10“6M, 107M, 10"8M, 10’9M, 1040M, 101M, 1042M, 1043M, or less. In some embodiments, an antibody described herein specifically binds trypsin 1 (e.g., a human or non-human primate trypsin 1) and trypsin 2 (e.g., a human or non-human primate trypsin 2) with binding affinity (e.g., as indicated by KD) of between 1x10-10M and 5x10-9M, between 1x10-10M and 1x10-9M, between 5x10-10and 1x10-9M, between 5x10-11and 1x10-10M, between 1x10-11and 5x10-10M, or between 5x10-13and 1x10-12M. For example, an antibody of the present disclosure can bind to a trypsin 1 protein (e.g., a human or non-human primate trypsin 1) and a trypsin 2 protein (e.g., a human or non-human primate trypsin 2) with an affinitybetween 1 pM and 500 nM, e.g., between 50 pM and 100 nM, between 500 pM and 50 nM, between 1 pM and 100 pM, between 10 pM and 100 pM, between 50 pM and 100 pM, between 100 pM and 500 pM, between 500 pM and 1 nM, between 1 nM and 5 nM, between 1 nM and 10 nM, between 5 nM and 25 nM, between 10 and 50 nM between 50 nM and 100 nM, between 100 n and 500 nM. The disclosure also includes antibodies that compete with any of the antibodies described herein for binding to a trypsin 1 protein (e.g., a human or non-human primate trypsin 1) and a trypsin 2 protein (e.g., a human or non-human primate trypsin 2) and that have an affinity of 100 nM or lower (e.g., 80 nM or lower, 50 nM or lower, 20 nM or lower, 10 nM or lower, 1 nM or lower, 500 pM or lower, 50 pM or lower, 10 pM or lower, or 5 pM or lower). The affinity and binding kinetics of an antibody can be tested using any suitable method including but not limited to biosensor technology (e.g., OCTET or BIACORE). In some embodiments, antibodies described herein binds to trypsin 1 and trypsin 2 with a KD of sub-nanomolar range.[000112] Binding affinity (or binding specificity) can be determined by a variety of methods including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance (SPR), florescent activated cell sorting (FACS) or spectroscopy (e.g., using a fluorescence assay). Exemplary conditions for evaluating binding affinity are in HBS-P buffer (10 mM HEPES pH7.4, 150 mM NaCl, 0.005% (v / v) surfactant P20) and PBS buffer (10 mM PO4-3, 137 mM NaCl, and 2.7 mM KCl). These techniques can be used to measure the concentration of bound proteins as a function of target protein concentration. The concentration of bound protein ([[Bound]]) is generally related to the concentration of free target protein ([[Free]]) by the following equation:[[Bound]] = [[Free]] / (Kd+[[Free]])[000113] It is not always necessary to make an exact determination of KA, though, since sometimes it is sufficient to obtain a quantitative measurement of affinity, e.g., determined using a method such as ELISA or FACS analysis, is proportional to KA, and thus can be used for comparisons, such as determining whether a higher affinity is, e.g., 2-fold higher, to obtain a qualitative measurement of affinity, or to obtain an inference of affinity, e.g., by activity in a functional assay, e.g., an in vitro or in vivo assay.[000114] Exemplary anti-trypsin 1 / trypsin 2 antibody sequences (e.g., heavy chain variable domain (VH) and light chain variable domain (VL), CDR sequences are provided in Tables la and lb.Table la: Exemplary Anti-trypsin 1 / trypsin 2 AntibodiesTrypsin 1 / Trypsin 2 Sequences SEQ ID NO AntibodyTrypsin HC CDR1 FTFSSYAMS 1 1 / Trypsin 2 - HC CDR2 AISASGGSTYYADSVKG 2 Dual-Ll- HC CDR3 ARG SP IGYS YARVSYYYYMDV 3 Abl LC CDR1 RASQGISRWLA 4LC CDR2 AAS SLQ S 5LC CDR3 QQGNSFPLT 6VH EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPG 57KGLEWVSAISASGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSPIGYSYARVSYYYYMDVWGKGTTVTVSSVL DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 58APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA T YYCQQGNSFPLTFGGGTKVE I K EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPG 141 KGLEWVSAISASGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSPIGYSYARVSYYYYMDVWGKGTTVTV HC 1 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFP P KP KD T LMI SRTP EVT C WVDVS HED P EVKFN WYVD GVE M428L / N43 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4A) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK L T VD K S RWQ QGN VF S C S VLHE ALHAH Y T Q K S L S L S P GK EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPG 142 KGLEWVSAISASGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSPIGYSYARVSYYYYMDVWGKGTTVTV HC 2 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFP P KP KD T LMI SRTP EVT C WVDVS HED P EVKFN WYVD GVE M428L / N43 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4S) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPG 143 KGLEWVSAISASGGSTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSPIGYSYARVSYYYYMDVWGKGTTVTV HC 3 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVF 5A / P329A; LFPPKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVE M252Y / S25 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4T / T256E) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKDIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 144APKLLIYAASSLQSGVPSRFSGSGSGTDFTLT I SSLQPEDFA TYYCQQGNSFPLTFGGGTKVEIKRTVAAP SVFIFPPSDEQLK LC SGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 FTFGDYAMW 7 1 / Trypsin 2 - HC CDR2 Al S ASGDVT Y YAD SVKG 8 Dual-Ll- HC CDR3 ARG S L I G Y S YARVS Y Y Y Y S D V 9 Ab2 LC CDR1 RASQGISRWLA 4LC CDR2 AASSI. QS 5 LC CDR3 QQGWSFPI. T 10 VH EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMWWVRQAPG 59KGLEWVSAISASGDVTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSLIGYSYARVSYYYYSDVWGKGTTVTV SS VL DIQMTQSPS SVS ASVGDRVT I T CRASQGI SRWLAWYQQKPGK 60APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQGWSFPLTFGGGTKVEIK EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMWWVRQAPG 145 KGLEWVSAISASGDVTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSLIGYSYARVSYYYYSDVWGKGTTVTV HC 1 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVE M428L / N43 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4A) KALAAP I E K T I S KAKG Q P RE P Q V Y T L P P S RD E L T KN Q V S L T C LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMWWVRQAPG 146 KGLEWVSAISASGDVTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSLIGYSYARVSYYYYSDVWGKGTTVTV HC 2 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVF 5A / P329A; LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVE M428L / N43 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4S) KAI. AAP I E K T I S K A K G Q P RE P Q V Y T L P P S RD E I. T KN Q V S L T C LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK EVQLLESGGGLVQPGGSLRLSCAASGFTFGDYAMWWVRQAPG 147 KGLEWVSAISASGDVTYYADSVKGRFTISRDNSKNTLYLQMN SLRAEDTAVYYCARGSLIGYSYARVSYYYYSDVWGKGTTVTV HC 3 (IgGlwith SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIL234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFP P KP KD T LYI TREP EVT C WVDVS HED P EVKFN WYVD GVE M252Y / S25 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4T / T256E) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK L T VD K S RWQ QGN VF SCSVMHEALHNHYTQKSLSLSPGK D I QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAWYQQKPGK 148 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLT I SSLQPEDFA LC TYYCQQGWSFPLTFGGGTKVEIKRTVAAP SVFIFPPSDEQLKSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 GSISSYYWS 11 1 / Trypsin 2 - HC CDR2 RIYTSGSTNYNPSLKS 12 Dual-L2- HC CDR3 ARDLTNYGSGKSIRFYGMDV 13 Ahl LC CDR1 QASQDISNYLN 14LC CDR2 DASNLET 15 LC CDR3 QQDDNF IT 16 VH QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAG 61KGLEWIGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGSGKSIRFYGMDVWGQGTTVTVSS VL DIQMTQSPSSLSASVGDRVTITCQASQDTSNYLNWYQQKPGK 62APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA T Y Y C QQDDNF I T F G G G T K VE I K QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAG 149 KGLEWIGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGSGKSIRFYGMDVWGQGTTVTVSS HC 1 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4A) LAAPIEKTI SKAKGQPREPQVYTLPP SRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAG 150 KGLEWIGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGSGKSIRFYGMDVWGQGTTVTVSS HC 2 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4S) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPAG 151 KGLEWIGRIYTSGSTNYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGSGKSIRFYGMDVWGQGTTVTVSS HC 3 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLYITREPEVTCWVDVSHEDPEVKFNWYVDGVEVH M252Y / S25 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4T / T256E) LAAP I E KT I S KAKGQP RE P QVY T LP P S RD E L T KNQ V S L T C LV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGKVFSCSVMHEALHNHYTQKSLSLSPGK DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 152 APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA T Y Y C QQDDNF I T F GGG T KVE I KRT VAAP S VF I F P P S D E Q LK S LC GTASWCLLNNFYPREAKVQWKVDNALQSGMSQESVTEQDSK KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECTrypsin HC CDR1 GSISSNYWH 17 1 / Trypsin 2 - HC CDR2 RIHTSGSTFYNPSLKS 18HC CDR3 ARD ITNYGSGKS IRFYPMDV 19Dual-L2- LC CDR1 QASQDISNYLN 14 Ab2 LC CDR2 DASNLET 15LC CDR3 QQDDTFIT 20 VH QVQLQESGPGLVKPSETLSLTCTVSGGSISSNYWHWIRQPAG 63KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDITNYGSGKSIRFYPMDVWGQGTTVTVSS VL DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 64APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA TYYCQQDDTFITFGGGTKVEIK QVQLQESGPGLVKPSETLSLTCTVSGGSISSNYWHWIRQPAG 153 KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDITNYGSGKSIRFYPMDVWGQGTTVTVSS HC 1 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVYA'DVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4A) LAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSNYWHWIRQPAG 154 KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDITNYGSGKSIRFYPMDVWGQGTTVTVSS HC 2 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA 4S) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSNYWHWIRQPAG 155 KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDITNYGSGKSIRFYPMDVWGQGTTVTVSS HC 3 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKD TLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEVH M252Y / S25 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4T / T256E) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DIQMTQSPSSLSASVGRRVTITCQASQDISNYLNWYQQKPGK 156 APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA TYYCQQDDTFITFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS LC GTASWCLLNNFYPREAKVQWKVDNALQSGMSQESVTEQDSK KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECTrypsin HC CDR1 GSISSHYWH 21 1 / Trypsin 2 - HC CDR2 RIATSGSTYYNP SLKS 22 Dual -1,2- HC CDR3 ARDLTNYGI TKS TRFYGMDV 23 Ab3 LC CDR1 QASQDISNYLN 14LC CDR2 DASNLET 15LC CDR3 QQVDNFIT 24VH QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 65KGLEWIGRIATSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGITKSIREYGMDVWGQGTTVTVSS VL DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 66APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA TYYCQQVDNFITFGGGTKVEIK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 157 KGLEWIGRIATSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGITKSIRFYGMDVWGQGTTVTVSS HC 1 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKD TLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4A) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 158 KGLEWIGRIATSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGITKSIRFYGMDVWGQGTTVTVSS HC 2 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4S) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSLGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 159 KGLE WI GRI ATSGSTYYNP SLKSRVTMSVD T S KNQF SLKL S S VTAADTAVYYCARDLTNYGITKSIRFYGMDVWGQGTTVTVSS HC 3 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEVH M252Y / S25 NAKTKPR. EEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4T / T256E) LAAPIEKTI SKAKGQPREPQVYTLPP SRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DTQMTQSPSSLSASVGERVTITCQASQDISNYLNWYQQKPGK 160 APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA TYYCQQVDNFITFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS LC GTASWCLLNNFYPREAKVQWKVDNALQSGMSQESVTEQDSK KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECTrypsin HC CDR1 GSISSHYWH 21 1 / Trypsin 2 - HC CDR2 RIHTSGSTFYNP SLKS 18 Dual-L2- HC CDR3 ARD L T N Y G W S K S I RF Y GMD V 25 Ab4 LC CDR1 QASQDISNYLN 14LC CDR2 DASNLET 15 LC CDR3 QQTDNFIT 26 VH QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 67KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSSVTAADTAVYYCARDLTNYGWSKSIREYGMDVWGQGTTVTVSSVL DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 68APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA T Y Y CQQTDNF I T F GGG T KVE I K QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 161 KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGWSKSIRFYGMDVWGQGTTVTVSS HC 1 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA 4A) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 162 KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGWSKSIRFYGMDVWGQGTTVTVSS HC 2 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKD TLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4S) LAAP I E KT I S KAKGQP RE P QVY T LP P S RD E L T KNQ V S L T C LV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 163 KGLEWIGRIHTSGSTFYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGWSKSIRFYGMDVWGQGTTVTVSS HC 3 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYTCN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEVH M252Y / S25 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4T / T256E) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 164 APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA TYYCQQTDNFITFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS LC GTASWCLLNNFYPREAKVQWKVDNALQSGMSQESVTEQDSK KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECTrypsin HC CDR1 GSISSHYWH 21 1 / Trypsin 2 - HC CDR2 RIATSGSTYYNPSLKS 22 Dual-L2- HC CDR3 ARDLTMYGITRSIRFYGMDV 165 Ab5 LC CDR1 QASQDISNYLN 14LC CDR2 DASNLET 15 LC CDR3 QQVDNFIT 24 VH QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 166KGLE WI GRI ATSGSTYYNP SLKSRVTMSVD T S KNQF SLKL S S VTAADTAVYYCARDLTNYGITRSIRFYGMDVWGQGTTVTVSS VL DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 66APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDTAT Y YCQQVDNF I T F GGG T KVE I KQVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 167KGLEWIGRIATSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGITRSIRFYGMDVWGQGTTVTVSS HC 1 (IgGl ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4A) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 168 KGLEWIGRIATSGSTYYNPSLKSRVTMSVDTSKNQFSLKLSS VTAADTAVYYCARDLTNYGITRSIRFYGMDVWGQGTTVTVSS HC 2 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN L234A / L23 VN H KP S N T K VD K K VE P K S C D K T H T C P P C P AP E AAG G P S VF L F 5A / P329A; PPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVH M428L / N43 NAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKA 4S) LAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLQESGPGLVKPSETLSLTCTVSGGSISSHYWHWIRQPAG 169 KGLE WI GRI ATSGSTYYNP SLKSRVTMSVD T S KNQF SLKL S S VTAADTAVY YCARDLTNYGITRSIRFYGMDVWGQGTTVTVSS HC 3 (IgGl ASTKGP SVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWN with SGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICN L234A / L23 VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLF 5A / P329A; PPKPKDTLYITREPEVTCWVDVSHEDPEVKFNWYVDGVEVH M252Y / S25 NAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKA 4T / T256E) LAAP I E KT I S KAKGQP RE P QVY T LP P S RD E L T KNQ V S L T C LV KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLT VDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DIQMTQSPSSLSASVGDRVTITCQASQDISNYLNWYQQKPGK 160 APKLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIA TYYCQQVDNFITFGGGTKVEIKRTVAAPSVFIFPPSDEQLKS LC GTASWCLLNNFYPREAKVQWKVDNALQSGMSQESVTEQDSK KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECTrypsin HC CDR1 YTFTGYYMH 27 1 / Trypsin 2 - HC CDR2 SINPSSGGTNYAQKFQG 28 Dual-L3- HC CDR3 ARVGGAAAAGKAYTASAFD I 29 AM LC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31 LC CDR3 QQFHNWPPLT 32 VH QVQ LVQ S GAE VKKP GA S VKV SC KASGYTF TGYYMHWVRQ AP G 69QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVS S VL EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAIAIYQQKPGQ 70APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IK HC 1 (IgGl QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TGY YMH WVRQ AP G 170 with QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS L234A / L23 RLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVS5A / P329A; SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWM428L / N43 NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC 4A) N VN H KP S N T KVP KKVE P K S C D K T H T C P P C P AP E AAGGP S VF L FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEV HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNK ALAAP IEKT I SKAKGQPREPQVYTLPP SRDELTKNQVSLTCL VKGFYP SPIAVEWESNGQPENN YKTTPPVLPSPGSFFLYSKL T VD K S RWQQ GNVF S C S VLH E AL HAH Y T QK S L S L S P GK QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPG 171 QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVS HC 2 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 5A / P329A; FPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV M428L / N43 HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNK 4S) ALAAP IEKT I SKAKGQPREPQVYTLPP SRDELTKNQVSLTCL VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TGY YMH WVRQ AP G 172 QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDT SI STAYMELS RLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVS HC 3 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 5A / P329A; FPPKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEV M252Y / S25 HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK 4T / T256E) ALAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 173APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFAVYYCQQFHNWPPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLLC KSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGECTrypsin HC CDR1 YTFTPHYMH 33 1 / Trypsin 2 - HC CDR2 AINP S SGGTAYAQKFQG 34 Dual-L3- HC CDR3 ARVGGAARVGKAYTASAFP I 35 Ab2 LC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31 LC CDR3 QQFHNWPPLT 32 VH QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TDH YMH WVRQ AP G 71QGLEWMGAINPSSGGTAYAQKFQGRVTMTRPTSISTAYMELS RLRSPPTAVYYCARVGGAARVGKAYTASAFDTWGQGTMVTVS S VL EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 70APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEPFA VYYCQQFHNWPPLTFGGGTKVE IK QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TDH YMH WVRQ AP G 174 HC 1 (IgGl QGLEWMGAINPSSGGTAYAQKFQGRVTMTRPTSISTAYMELS with RLRSPPTAVYYCARVGGAARVGKAYTASAFDIWGQGTMVTVS L234A / L23 SASTKGPSVFPLAPSSKSTSGGTAALGCLVKPYFPEPVTVSW 5A / P329A; NSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC M428L / N43 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 4A) FPPKPKDTLMISRTPEVTCVWPVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKALAAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL VKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KA S G YTF TDH YMH WVRQ AP G 175 QGLEWMGAINPSSGGTAYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARVGGAARVGKAYTASAFDIWGQGTMVTVS HC 2 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 5A / P329A; FPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV M428L / N43 HNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK 4S) ALAAP IEKT I SKAKGQPREPQVYTLPP SRDELTKNQVSLTCL VKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGKQVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TDH YMH WVRQ AP G 176 QGLEWMGAINPSSGGTAYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARVGGAARVGKAYTASAFDIWGQGTMVTVS HC 3 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 5A / P329A; FPPKPKD TLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEV M252Y / S25 HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNK 4T / T256E) ALAAP I E KT I S KAKGQ P RE P QV Y T LP P SRDEL TKN QV S L T C L VKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 173 APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IKRTVAAP SVFIFPP SDEQL LC KSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKD STYSLS STLTLSKADYEKHKVYACEVTHQGLS SPVTKSF NRGECTrypsin HC CDR1 YTFTGYYMH 27 1 / Trypsin 2 - HC CDR2 S INP S SGGTNYAQKFQG 28 Dual -13- HC CDR3 ARVGGAAAAGKAYTASAFD I 29 Ab3 LC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31 LC CDR3 QQFHNWPPLT 32 VH QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TGY YMH WVRQ AP G 233QGLEWMGSINPSSGGTNYAQKFQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVSVL EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 70APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IK QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPG 234 QGLEWMGSINPSSGGTNYAQKFQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVS HC 1 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVN H KP S N T KVD KKVE P K S C D K T H T C P P C P AP E AAGGP S VF L 5A / P329A; FPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV M428L / N43 HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNK 4A) ALAAP IEKT I SKAKGQPREPQVYTLPP SRDELTKNQVSLTCL VKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGKQVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWRQAPG 235QGLEWMGSINPSSGGTNYAQKFQGRVTMTTDTSTSTAYMELR SLR SDD TAVYYCARVGGAAAAGKAYTASAFDI WGQGTMVTVS HC 2 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 5A / P329A; FPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEV M428L / N43 HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNK 4S) ALAAPIEKT I SKAKGQPREPQVYTLPP SRDELTKNQVSLTCL VKGFYP SDIAVEWESNGQPENN YKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPG 236 QGLEWMGSINPSSGGTNYAQKFQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARVGGAAAAGKAYTASAFDIWGQGTMVTVS HC 3 (IgGl SASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSW with NSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYIC L234A / L23 NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFL 5A / P329A; FPPKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEV M252Y / S25 HNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNK 4T / T256E) ALAAPIEKT I SKAKGQPREPQVYTLPP SRDELTKNQVSLTCL VKGFYP SDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 173 APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IKRTVAAP SVFIFPP SDEQL LC KSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD S KD S T Y S L S S T L T L S KAD Y E KH KV YAC E VT HQ GL S S P V T K S F NRGECTrypsin HC CDR1 YTFTSYGIS 36 1 / Trypsin 2 - HC CDR2 WI SAYSGDTNYAQKLQG 37 Dual-L4- HC CDR3 ARG D E VVGKMT Y Y YGMD V 38 AM LC CDR1 RA S Q G I S RW LA 4LC CDR2 AASSLQS 5 LC CDR3 QQANSFPIT 39 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPG 72QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKMTYYYGMDVWGQGT TVTVS S VL DIQMTQSPS SVS ASVGLRVT I T CRASQGI SRWLAWYQQKPGK 73APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIK QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPG 177 QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARGDEVVGKMTYYYGMDVWGQGTTVTVSSAHC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSwith GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVL234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP5A / P329A; PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNM428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL4A) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGHC 2 (IgGl 178QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR with SLR SDD TAVYYCARGDEWGKMTYYYGMDVWGQGT TVTVS SA L234A / L23 STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS 5A / P329A;GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVM428L / N43 NHKPSNTKVDKKVEPKSCEKTHTCPPCPAPEAAGGPSVFLFP 4S) PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPG 179 QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAV Y YCARGDEWGKMTYYYGMDVWGQGT TVTVS SA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAP I E K T I S KAK GQ P RE P Q V Y T L P P S R D E L T KN Q V S L T C L VK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV D K S RWQQGNVF S C S VMH E ALHN H Y T Q K S L S L S P GK DTQMTQSPSSVSASVGERVTITCRASQGISRWLAWYQQKPGK 180 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIKRTVAAP SVFIFPPSDEQLK LC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTDYAIS 40 1 / Trypsin 2 - HC CDR2 WI SASTADTNYAQKLQG 41 Dual-L4- HC CDR3 ARGDEVVGKMTYYYGMDV 38 Ab2 LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQANSFPIT 39 VH QVQ LVQ S GAE VKKP GA S VK V SC KASGYTF TDYAIS WVRQ AP G 74QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKMTYYYGMDVWGQGT TVTV S S VL D T QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAW YQQKP GK 73APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIK QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 181QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELRSLRSDDTAVYYCARGDEVVGKMTYYYGMDVWGQGTTVTVSSAHC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSwith GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVL234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP5A / P329A; PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNM428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL4A) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 182 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR HC 2 (IgGl SLRSDD TAVYYCARGDEWGKMTYYYGMDVWGQGT TVTVS SA with STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS L234A / L23 GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV 5A / P329A; NHKPSNTKVDKKVEPKSCEKTHTCPPCPAPEAAGGPSVFLFP M428L / N43 PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN 4S) AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALAAP I E K T I S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VKGFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TD YAI S WVRQ AP G 183 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAV Y YCARGDEWGKMTYYYGMDVWGQGT TVTVS SA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAP I E K T I S KAKGQP REP Q VY T LP P S RD E L T KNQ V S L T C LV K GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 180 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIKRTVAAPSVFIFPPSDEQLK LC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTDYAIS 40 1 / Trypsin 2 - HC CDR2 WI SASTADTNYAQKLQG 41 Dual-L4- HC CDR3 ARGDEVVGKRTYYIGMDV 42 Ab3 LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQANSFPIT 39 VH QVQ LVQ S GAE VKKP GA S VK V SC KASGYTF TD YAI S WVRQ AP G 75QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTV S S VL D I QMTQ SP S SV S ASVGDRVT I T CRASQGI SRWLAW YQQKP GK 73APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIK QVQ LVQ S GAE VKKP GA S VK V S C KAS G YTF TD YAI S WVRQ AP G 184 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTV S SA HC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4A) A AP I E K T I S K A K G Q P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KA S G YTF TD YAI S WVRQ AP G. 185 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA HC 2 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV L234A / L23 NHKP SN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL4S) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGKHC 3 (IgGl QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TD YAI S WVRQ AP G 186 with QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELRL234A / L23 SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA5A / P329A; STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS M252Y / S25 GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV 4T / T256E) NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL AAP I E K T I S KAKGQP REP Q VY T LP P S RD E L T KNQ V S L T C LVK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV D K S RWQ QGN VF S C S VMHE ALHN H Y T Q K S L S L S P GK DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 180 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIKRTVAAPSVFIFPPSDEQLK LC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTF TDYAIS 40 1 / Trypsin 2 - HC CDR2 WI SASTADTNYAQKLQG 41 Dual-L4- HC CDR3 ARGTEVVGKMTVYLGMDV 43 AM LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQANSFPIT 39 VH QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TDYAIS WVRQ AP G 76QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGTEVVGKMTVYLGMDVWGQGT TVTVS S VL D I QMTQ SP S SV S ASVGDRVT I T CRASQGI SRWLAW YQQKP GK 73APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVE1KQVQ LVQ S GAE VKKP GA S VK V S C KAS G YTF TDYAIS WVRQ AP G 187 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGTEVVGKMTVYLGMDVWGQGT TVTV S SA HC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GAL T S G VH T F P A VL Q S S GL Y S L S S V V T V P S S S L G T Q T Y I C NV L234A / L23 NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4A) A AP I E K T I S K A K G Q P R E P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KA S G YTF TD YAI S WVRQ AP G. 188 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGTEVVGKMTVYLGMDVWGQGT TVTVS SA HC 2 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKP SN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKAL 4S) AAP I E K T I S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C LVK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGKQVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TD YAI S WVRQ AP G 189 HC 3 (IgGl QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR with SLRSDD TAVYYCARGTEVVGKMTVYLGMDVWGQGT TVTVS SA L234A / L23 STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS 5A / P329A; GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV M252Y / S25 NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 4T / T256E) PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALA AP I E K T I S K A K G Q P R E P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV D K S RWQ QGN VF S C S VMHE ALHN H Y T Q K S L S L S P GK D I QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAW YQQKP GK 180 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIKRTVAAP SVFIFPPSDEQLK LC SGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTDYAIS 40 1 / Trypsin 2 - HC CDR2 WISASTADTNYAQKLQG 41 Dual-L4- HC CDR3 ARQ D E VVGKMT Y Y I GT D V 44 Ab5 LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQANSFPLT 45 VH QVQ LVQ S GAE VKKP GA S VKVS C KA SG YTF TD YAI S WVRQ AP G 77QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARQDEVVGKMTYYIGTDVWGQGTTVTVSS VL DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 78APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA T YYCQQANSFPLTFGGGTKVE I PtQVQ LVQ S GAE VKKP GA S VKVS C KA S G YTF TD YAI S WVRQ AP G 190 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARQDEWGKMTYYIGTDVWGQGT TVTVS SA HC 1 (IgGlwith STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVL234A / L23 NHKP SN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKAL 4A) AAP I E K T I S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFL YSKLT'V DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGKQVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TD YAI S WVRQ AP G 191 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARQDEWGKMTYYIGTDVWGQGT TVTVS SA HC 2 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL4S) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VK V S C KAS G YTF TD YAI S WVRQ AP G 192 QGLEWMGWISASTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARQDEWGKMTYYIGTDVWGQGT TVTV S SA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GAL T S G VH T F P A VL Q S S GL Y S L S S V V T V P S S S L G T Q T Y I C NV L234A / L23 NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV D K S RWQ QGN VF S C S VMHE ALHN H Y T Q K S L S L S P GK D I QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAW YQQKP GK LC 193APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIKRTVAAPSVFIFPPSDEQLK SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTDYAIS 40 1 / Trypsin 2 - HC CDR2 WISAGTADTNYAQKLQG 46 Dual-L4- HC CDR3 ARGDEVVGKMTYYYDMDV 47 Ab6 LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQASSFPIT 48 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 79QGLE WMGWI SAGTADTNYAQKLQGRVTMT TD T S T S TAYMELR SLRSDD TAV Y YCARGDEWGKMTYYYDMDVWGQGT TVTVS S VL DIQMIQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 80APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQASSFPITFGGGTKVEIK QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 194 QGLE WMGWI SAGTADTNYAQKLQGRVTMT TD T STS TAYMELR SLRSDD TAVYYCARGDEWGKMTYYYDMDVWGQGT TVTVS SA HC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKAL 4A) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFL YSKLT'V DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGKQVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TD YAI S WVRQ AP G 195 QGLEWMGWISAGTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKMTYYYDMDVWGQGT TVTVS SA HC 2 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4S) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYP SD IAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TD YAI S WVRQ AP G 196 QGLEWMGWISAGTADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKMTYYYDMDVWGQGT TVTVS SA HC 3 (IgGlwith STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GAL T S G VH T F P A VL Q S S GL Y S L S S V V T V P S S S L G T Q T Y I C NVL234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLYITREPEVTCVWDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYP SD IAVEWE SNGQPENNYKTTPPVLDSDGSFFLYSKLTV D K S RWQ QGN VF S C S VMHE ALHN H Y T Q K S L S L S P GK DIQMIQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 197 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQASSFPITFGGGTKVEIKRTVAAPSVFIFPPSDEQLKLC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECHC CDR1 YTFDDYGIS 49Trypsin HC CDR2 WISATVADTNYAQKLQG 50 1 / Trypsin 2 - HC CDR3 ARGDEPVGKMTYYYGMDV 51 Dual-L4- LC CDR1 RASQGISRWLA 4 Ab7 LC CDR2 AASSLQS 5LC CDR3 QQANSLPIT 52 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFDDYGISWVRQAPG 81QGLEWMGWISATVADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARGDEPVGKMTYYYGMDVWGQGTTVTVSS VL DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 82APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSLPITFGGGTKVEIK QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTFDD YGI S WVRQ AP G 198 QGLEWMGWISATVADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARGDEPVGKMTYYYGMDVWGQGTTVTVSSA HC 1 (IgGlwith STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVL234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4A) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFDDYGISWVRQAPG 199 QGLE WMGWI SATVADTNYAQKLQGRVTMT TE T S T S TAYMELR SLRSDDTAVYYCARGDEPVGKMTYYYGMDVWGQGTTVTVSSA HC 2 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMISRTPEVTCWVEVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4S) AA P I E K T I S KAK GQ P RE P Q V Y T L P P S R D E L T KN Q V S L T C L VK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFDDYGISWVRQAPG 200 QGLEWMGWISATVADTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDTAVYYCARGDEPVGKMTYYYGMDVWGQGTTVTVSSA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAP I E K T T S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VK GF YP SE IAVEWE SNGQPENNYKTTPPVLE SEGSFFLYSKLTV E K S RWQ QGN VF S C S VMHE ALHN H Y T Q K S L S L S P GK E I QMTQ SP S SVS ASVGERVT T T CRASQGI SRWLAWYQQKP GK 201 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEEFA TYYCQQANSLPITFGGGTKVEIKRTVAAP SVFIFPPSEEQLK LC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTDYAIS 40 1 / Trypsin 2 - HC CDR2 WISASTADANYAQKLQG 202 Dual-L4- HC CDR3 ARGDEVVGKRTYYIGMDV 42 AbS LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5LC CDR3 QQASSFPIT 48VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 203QGLEWMGWISASTADANYAQKLQGRVTMTTDTSTSTAYMELR SLR SDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS S VL D I QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAW YQQKP GK 204APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQASSFPITFGGGTKVEIK QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TD YAI S WVRQ AP G 205 QGLEWMGWISASTADANYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA HC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4A) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TD YAI S WVRQ AP G 206 QGLEWMGWISASTADANYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA HC 2 (IgGlSTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL4S) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 207 QGLEWMGWISASTADANYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 208 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQASSFPITFGGGTKVEIKRTVAAPSVFIFPPSDEQLKLC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTDYAIS 40 1 / Trypsin 2 - HC CDR2 WISASTADINYAQKLQG 216 Dual-L4- HC CDR3 ARGDEVVGKRTYYIGMDV 42 Ab9 LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQASSFPIT 48 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYAISWVRQAPG 217QGLEWMGWISASTADINYAQKLQGRVTMTTDTSTSTAYMELRSLR SDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SVL DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 204APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQASSFPITFGGGTKVEIK QVQ LVQ S GAE VKKP GA S VKVS C KA SG YTF TD YAI S WVRQ AP G 218 QGLEWMGWISASTADINYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA HC 1 (IgGlwith STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVL234A / L23 NHKP SN TKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKAL 4A) AAP I E K T I S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TD YAI S WVRQ AP G 219 QGLEWMGWISASTADINYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTVS SA HC 2 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4S) AAP I E K T I S KAKGQP REP Q VY T LP P S RD E L T KNQ V S L T C LV K GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VK V S C KAS G YTF TD YAI S WVRQ AP G 220 QGLEWMGWISASTADINYAQKLQGRVTMTTDTSTSTAYMELR SLRSDD TAVYYCARGDEWGKRTYYIGMDVWGQGT TVTV S SA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKP SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVFLFP 5A / P329A; PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) A AP I E K T I S K A K G Q P R E P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYP SD IAVEWE SNGQPENNYKTTPPVLD SDGSFFLYSKLTV D K S RWQ QGN VF S C S VMHE ALHN H Y T Q K S L S L S P GK D I QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAW YQQKP GK 208 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQASSFPITFGGGTKVEIKRTVAAPSVFIFPPSDEQLK LC SGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTSYGIS 36 1 / Trypsin 2 - HC CDR2 WI SAYSGDTNYAQKLQG 37 Dual-L4- HC CDR3 ARGDEVVGKMTYYYGMDV 38 AblO LC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5 LC CDR3 QQANSFPIT 39 VH QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPG 237QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDMAVYYCARGDEWGKMTYYYGMDVWGQGTTVTVSS VL D I QMTQ SP S SVS ASVGDRVT I T CRASQGI SRWLAWYQQKP GK 73APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQANSFPITFGGGTKVEIKQVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWRQAPG 238QGLE WMGWI SAYSGDTNYAQKLQGRVTMT TD T STS TAYMELR SLRSDDMAVYYCARGDEWGKMTYYYGMDVWGQGTTVTVSSA HC 1 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMISRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4A) AAP I E K T I S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VK GF YP SD IAVEWE SNGQPENN YKTTPPVLD SDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWRQAPG 239 QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDMAVYYCARGDEWGKMTYYYGMDVWGQGT TVTVS SA HC 2 (IgGlwith STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS GALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYICNVL234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLMI SRTPEVTCWVDVSHEDPEVKFNWYVDGVEVHN M428L / N43 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4S) AAP I E K T I S KAK GQ P RE P Q V Y T L P P S RD E L T KN Q V S L T C L VK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPG 240 QGLEWMGWISAYSGDTNYAQKLQGRVTMTTDTSTSTAYMELR SLRSDDMAVYYCARGDEWGKMTYYYGMDVWGQGTTVTVSSA HC 3 (IgGl STKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNS with GALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV L234A / L23 NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP 5A / P329A; PKPKDTLYITREPEVTCVVVDVSHEDPEVKFNWYVDGVEVHN M252Y / S25 AKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL 4T / T256E) AAP I E K T T S KAKGQP REP Q VY T LP P S RD E L T KNQ V S L T C LVK GFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV D K S RWQ QGN VF S C S VMH E ALHN H Y T Q K S I. S I. S P GK DIQMTQSPSSVSASVGDRVTITCRASQGISRWLAWYQQKPGK 180 APKLLIYAASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFA TYYCQQANSFPITFGGGTKVEIKRTVAAPSVFIFPPSDEQLK LC SGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDS KDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFN RGECTrypsin HC CDR1 YTFTGYYMH 27 1 / Trypsin 2 - HC CDR2 SINPSSGGTNYAQKFQG 28 Dual-L5- HC CDR3 ARD P VLLLRQQRI LHE SAF D I 53 AM LC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31 LC CDR3 QQFHNWPPLT 32 VH QV Q LVQ S GAE VKKP GA S VK V SC KASGYTF TGY YMH WVRQ AP G 83QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARDPVLLLRQQRILHESAFDIWGQGTTVTV VL EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 70APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IK HC 1 (IgGl QVQ LVQ S GAE VKKP GA S VKVS C KASGYTF TGY YMH WVRQ AP G 209 with QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS L234A / L23 RLRSDDTAVYYCARDPVLLLRQQRILHESAFDIWGQGTTVTV5A / P329A; SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSM428L / N43 WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI 4A) CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVF LFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVE VHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSN KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK L T VD K S RW Q QGN VF S C S VLHE ALHAH Y T Q K S L S L S P GK QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TGY YMH WVRQ AP G 210 QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARDPVLLLRQQRILHESAFDIWGQGTTVTV HC 2 (IgGlSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFP P KP KD T LMI SRTP EVT C WVDVS HED P EVKFN WYVD GVE M428L / N43 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4S) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTF TGY YMH WVRQ AP G 212 QGLEWMGSINPSSGGTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARDPVLLLRQQRILHESAFDIWGQGTTVTV HC 3 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFP P KP KD T LYI TREP E VTCVWDV S HED P EVKFN WYVD GVE M252Y / S25 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4T / T256E) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSD IAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK ETVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 173 APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IKRTVAAP SVFIFPP SDEQL LC KSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD SKD STYSLS STLTLSKADYEKHKVYACEVTHQGLS SPVTKSF NRGECTrypsin HC CDR1 YTFEGHYMH 54 1 / Trypsin 2 - HC CDR2 A I N P Y S G Q T N YA Q K F Q G 55 Dual-L5- HC CDR3 ARDFVLLLRQSRILHESAFDI 56 Ab2 LC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31 LC CDR3 QQFHNWPPLT 32 VH QVQ LVQ S GAE VKKP GA S VKVS C KAS G YTFEGHYMH WVRQAP G 84QGLEWMGAINPYSGQTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARDFVLLLRQSRILHESAFDIWGQGTTVTVc>c>VL ETVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 70APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IK QVQLVQSGAEVKKPGASVKVSCKASGYTFEGHYMHWVRQAPG HC 1 (IgGl 213QGLEWMGAINPYSGQTNYAQKFQGRVTMTRDTSISTAYMELSwith RLRSDDTAVYYCARDFVLLLRQSRILHESAFDIWGQGTTVTV L234A / L23 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS 5A / P329A; WNSGALTSGVHTFPAVLQSSGLYSLSSWTVPSSSLGTQTYI M428L / N43 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 4A)LFP P KP KD T LMI SRTP EVT C WVDVS HED P EVKFN WYVD GVEVHNAKTKPREEQYNSTYRWSVLTVLHQDWLNGKEYKCKVSNKAL AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVLHEALHAHYTQKSLSLSPGK QVQ LVQ S GAE VKKP GA S VKV S C KAS G YTFEGH YMH WVRQ AP G 214 QGLEWMGAINPYSGQTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARDFVLLLRQSRILHESAFDIWGQGTTVTV HC 2 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WN S GAL T S G VH T F P AVLQ S S GL Y S L S S W T VP S S S L G T Q T Y I L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGP SVF 5A / P329A; LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVE M428L / N43 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4S) KAL AAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVLHEALHSHYTQKSLSLSPGK QVQLVQSGAEVKKPGASVKVSCKASGYTFEGHYMHWVRQAPG 215 QGLEWMGAINPYSGQTNYAQKFQGRVTMTRDTSISTAYMELS RLRSDDTAVYYCARDFVLLLRQSRILHESAFDIWGQGTTVTV HC 3 (IgGl SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS with WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYI L234A / L23 CNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF 5A / P329A; LFPPKPKDTLYITREPEVTCWVDVSHEDPEVKFNWYVDGVE M252Y / S25 VHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSN 4T / T256E) KALAAPIEKTI SKAKGQPREPQVYTLPPSRDELTKNQVSLTC LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK L T VD K S RWQ QGN VF S C S VMHE ALHNH Y T Q K S L S L S P GK EIVMTQSPATLSVSPGERATLSCRASQSVGSNLAWYQQKPGQ 173 APRLLIYGASTRATGIPARFSGSGSGTEFTLTISSLQSEDFA VYYCQQFHNWPPLTFGGGTKVE IKRTVAAP SVFIFPP SDEQL LC KSGTASWCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQD S KD S T Y S L S S T L T L S KAD Y E KH KVYAC E VT HQ GL S S P VT K S FNRGEC[000115] In some embodiments, certain amino acid positions in an antibody described herein (e.g., amino acids in the VH / VL regions and / or CDR regions) are substitutable and the substitution results in an antibody with substantially similar binding and biological activities (e.g., substantially similar binding affinity, binding specificity, protease activity inhibitory activity, anti-inflammatory activity, or a combination thereof) as the reference antibody. In order to identify a substitutable position of an antibody, the amino acid sequence of that antibody is compared to the sequences of other antibodies belonging to the same group as that antibody. If the identity of that amino acid varies between the different related antibodies of a group at any particular position, that position is a substitutable position of the antibody. In other words, a substitutable position is a position in which the identity of the amino acid varies between the related antibodies. Positions that contain a constant amino acid are not substitutable positions.[000116] In some embodiments, the above method may be employed to provide a consensus antibody sequence. In such a consensus sequence, a non-substitutable position is indicated by the amino acid present at that position, and a substitutable position is indicated as an " X".[000117] Depending on how the antibodies are to be employed, X may be a) any amino acid, b) any amino acid present at that position in any of the related antibodies in the group or a conservatively substituted variant thereof or c) any amino acid present at that position in any of the related antibodies in the group. Any antibody having a sequence that is encompassed by the consensus should bind to the same antigen as any of the related antibodies.[000118] Tn some embodiments, the method described above may be employed in methods of designing and making a variant of a parental antibody that at least maintains (e.g., maintains or increases) the antigen binding activity of the parental antibody. Because antibodies containing substitutions at substitutable positions have already been produced and tested, substitutions at those posi tions can be made in the knowledge that they should not significantly decrease the binding activity of the antibody. In general, an antibody variant of a parental antibody has an antigen binding affinity that is at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 100% (e.g., at least 150%, at least 200%, at least 500%, at least 1000%, usually up to at least 10,000%) of the binding affinity of the parental antibody to a particular antigen.[000119] In some embodiments, a substitutable position of a parental antibody may be substituted by a) any of the 20 naturally occurring amino acids to produce random substitutions, b) an amino acid having biochemical properties similar to the amino acid already present at the substitutable position to produce conservative substitutions, c) an amino acid that is present at the same position in a related antibody to produce a directed substitution, or d) an amino acid that is present at the same position in a similar human antibody to produce a humanizing substitution. A substitution may be made at any part of an antibody variable region, including any framework region or CDR. In certain embodiments, a single substitutable amino acid may be substituted. However, in other embodiments, a plurality of substitutable amino acids (e.g., up to about 5 or 10 or more) may be substituted. In particular embodiments, the type of substitution that can be made at each substitutable position may be indicated by the types of amino acids present at that position in the related antibodies. For example, if unrelated amino acids (e.g., Ala, Gly, Cys, Glu and Thr) are present at a certain position of a group of related antibodies, then anyamino acid could be substituted at that position without significantly reducing binding activity of the antibody.[000120] Exemplary amino acids substitutions of an anti-trypsin 1 / trypsin 2 antibody described herein are set forth in Table lb:Table lb. Exemplary Anti-Trypsin 1 / Trypsin 2 Antibody Amino Acid Substitutions Trypsin 1 / Tryi osin 2 Sequences SEQ ID NO Trypsin HC CDR1 FTFXiX2YAMX385 1 / Trypsin 2 - XI is S or GDual-Ll- X2is S or DAbO X3is S or WHC CDR2 AISASGX4X5TYYADSVKG 86X3is G or DXs is S or VHC CDR3 ARGSX6IGYSYARVSYYYYX7DV 87X6is P or LX? is M or SLC CDR1 RASQGISRWLA 4LC CDR2 AASSLQS 5LC CDR3 QQGXgSFPLT 88X3is N or WTrypsin HC CDR1 GSI SSXIYWX289 1 / Trypsin 2 - XI is Y, N, or HDual-L2- X2is S or HAbO HC CDR2 R I X3T S G S T X 4 Y N P S L K S 90X3is Y, H, or AX4is N, F, or YHC CDR3 ARDX5TNYGX6X7X8SIX9FYX10MDV 91Xs is L or IX6is S, I, or WX7 is G, T, or SXgis K or RX3is F or RX10is G or PLC CDR1 QASQDISNYLN 14LC CDR2 DASNLET 15LC CDR3 QQX11DX12FIT 92Xu is D, V, or TXi2is N or TTrypsin HC CDR1 YTFTX1X2YMH 93 1 / Trypsin 2 - XI is G or DDual-L3- X2is Y or HAbO HC CDR2 X3INPSSGGTX4YAQKFQG 94X3is S or AX4is N or AHC CDR3 ARVGGAAX5X6GKAYTASAFDI 95X5is A or RXg is A or VLC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31LC CDR3 QQFHNWPPLT 32 Trypsin HC CDR1 YTFX1X2YX3IS 96 1 / Trypsin 2 - Xi T or DDual-L4- X2is S or DAbO X3is G or AHC CDR2 WISAX4X5X6DX7NYAQKLQG 97X4is Y, S, G, or TX5is S, T, or VXs is G or AX? is T, I, or AHC CDR3 ARXgXsEXinVGKXi i TXu YXi 3X14X15DV 98X3is G or QXsis D or TXio is V or PXn is M or RX12 is Y or VXi 3 is Y, I, or LXi4 is G or DXis is M or TLC CDR1 RASQGISRWLA 4 LC CDR2 AASSLQS 5 LC CDR3 QQAX16SX17PXlgT 99Xis is N or SX- 7 is F or LXis is I or LTrypsin HC CDR1 YTFX1GX2YMH 100 1 / Trypsin 2 - Xi is T or EDual-L5- X2is Y or HAbO HC CDR2 X3INPX4SGX5TKYAQKFQG 101X3is S or AX4is S or YX5is G or QHC CDR3 ARDX6VLLLRQX7RILHESAFDI 102X6is P or FX? is Q or SLC CDR1 RASQSVGSNLA 30LC CDR2 GASTRAT 31LC CDR3 QQFHNWPPLT 32[000121] In some embodiments, an antibody of the present disclosure comprises a HC CDR1 comprising the amino acid sequence of FTFX1X2YAMX3 (SEQ ID NO: 85), in which Xi is S or G, X2 is S or D, or X3 is S or W; a HC CDR2 comprising the amino acid sequence of AISASGX4X5TYYADSVKG (SEQ ID NO: 86). in which X4is G or D, or X5is S or V; a HC CDR3 comprising the amino acid sequence of ARGSX6IGYSYARVSYYYYX7DV (SEQ ID NO: 87), in which X6is P or L, X7is M or S; a EC CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 comprising the amino acid sequence of QQGX8SFPLT (SEQ ID NO: 88), in which X8is N or W.[000122] In some embodiments, an antibody of the present disclosure comprises a HC CDR1 comprising the amino acid sequence of GSISSX1YWX2 (SEQ ID NO: 89), in which Xi is Y, N, or H, or X2 is S or H; a HC CDR2 comprising the amino acid sequence of RIX3TSGSTX4YNPSLKS (SEQ ID NO: 90). in which X3is Y, H. or A. or X4is N, F, or Y; a HC CDR3 comprising the amino acid sequence of ARDX5TNYGX6X7X8SIX9FYX10MDV (SEQ ID NO: 91), in which X5is L or I, X6is S. I, or W, X? is G, T, or S. X8is K or R, X9is F or R, X10 is G or P; a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 14; a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 comprising the amino acid sequence of QQX9DX10FIT (SEQ ID NO: 92), in which X9 is D, V, or T, or X10 is N or T.[000123] Tn some embodiments, an antibody of the present disclosure comprises a HC CDR1 comprising the amino acid sequence of YTFTX1X2YMH (SEQ ID NO: 93), in which Xi is G or D, or X2 is Y or H; a HC CDR2 comprising the amino acid sequence of X3INPSSGGTX4YAQKFQG (SEQ ID NO: 94), in which X3is S or A, or X4is N or A; a HC CDR3 comprising the amino acid sequence of ARVGGAAXsXeGKAYTASAFDI (SEQ ID NO: 95), in which X5 is A or R, or Xe is A or V; a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 30; a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 32.[000124] In some embodiments, an antibody of the present disclosure comprises a HC CDR1 comprising the amino acid sequence of YTFXIX2YX3IS (SEQ ID NO: 96), in which Xi is T or D, X2 is S or D, or X2 is G or A; a HC CDR2 comprising the amino acid sequence of WISAX4X5X6DX7NYAQKLQG (SEQ ID NO: 97), in which X4is Y, S, G, or T, X5is S, T, or V, Xe is G or A, X7is T, I, or A; a HC CDR3 comprising the amino acid sequence of ARX8X9EXioVGKXiiTXi2YXi3Xi4Xi5DV (SEQ ID NO: 98), in which X8is G or Q, X9is D or T, X10 is V or P, Xu is M or R, X12 is Y or V, X13 is Y, I, or L, X14 is G or D, or X15 is M or T; a LC CDR1 comprising the amino acid sequence of SEQ ID NO: 4; a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 comprising the amino acid sequence of QQAXI6SXI7PXI8T (SEQ ID NO: 99), in which Xi6is N or S, X17 is F or L, or Xi8is I or L.[000125] In some embodiments, an antibody of the present disclosure comprises a HC CDR1 comprising the amino acid sequence of YTFX1GX2YMH (SEQ ID NO: 100), in which Xi is T or E, or X2 is Y or H; a HC CDR2 comprising the amino acid sequence ofX3INPX4SGX5TNYAQKFQG (SEQ ID NO: 101), in which X3is S or A, X4is S or Y, or X5 is G or Q; a HC CDR3 comprising the amino acid sequence of ARDX6VLLLRQX7RILHESAFDI (SEQ ID NO: 102), in which Xc> is P or F, X7 is Q or S; a EC CDR1 comprising the amino acid sequence of SEQ ID NO: 30; a LC CDR2 comprising the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 comprising the amino acid sequence of SEQ ID NO: 32.[000126] In some embodiments, an antibody of the present disclosure comprises one or more of the HC CDRs (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. In some embodiments, an antibody of the present disclosure comprises the HC CDR3 amino acid sequences from any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. In some embodiments, an antibody of the present disclosure comprise the HC CDR1, HC CDR2, and HC CDR3 as provided for any one of the anti-trypsin 1 / trypsin 2 antibodies elected from Tables la and lb. In some embodiments, an antibody of the present disclosure comprises the LC CDR3 amino acid sequences from any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. In some embodiments, an antibody of the present disclosure comprises one or more of the LC CDRs (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of the antitrypsin 1 / trypsin 2 antibodies selected from Tables la and lb. In some embodiments, an antibody of the present disclosure comprise the LC CDR1, LC CDR2, and LC CDR3 s provided for any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb.[000127] In some embodiments, an antibody of the present disclosure comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 as provided for any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. hi some embodiments, antibody heavy and / or light chain CDR3 domains may play a particularly important role in the binding specificity / affinity of an antibody for an antigen. Accordingly, an antibody of the disclosure may include at least the heavy and / or light chain CDR3s of any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb.[000128] Also within the scope of the present disclosure are variants of any of the exemplary anti-trypsin 1 / trypsin 2 antibodies as disclosed herein. A variant may contain one or more amino acid residue variations in the VH and / or VL, or in one or more of the HC CDRs and / or one or more of the LC CDRs as relative to the reference antibody, while retaining substantially similar binding and biological activities (e.g., substantially similar binding affinity, binding specificity,protease activity inhibitory activity, anti-inflammatory activity, or a combination thereof) as the reference antibody.[000129] In some embodiments, an antibody of the disclosure have one or more CDRs (e.g., HC CDR or LC CDR) sequences substantially similar to any of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 sequences from one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. In some embodiments, the position of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2. or HC CDR3) and / or VL (e.g.. LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary by one, two, three, four, five, or six amino acid positions so long as specific binding to trypsin 1 (e.g., human or non¬ human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived). For example, in some embodiments, the position defining a CDR of any antibody described herein can vary by shifting the N-terminal and / or C -terminal boundary of the CDR by one, two, three, four, five, or six amino acids, relative to the CDR position of any one of the antibodies described herein, so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived), hi another embodiment, the length of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) region of an antibody described herein can vary (e.g., be shorter or longer) by one, two, three, four, five, or more amino acids, so long as immunospecific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived).[000130] Accordingly, in some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids shorter than one or more of the CDRs described herein (e.g., CDRS from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-humanprimate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein may be one, two, three, four, five or more amino acids longer than one or more of the CDRs described herein (e.g., CDRs from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). Tn some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the amino portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%,at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, the carboxy portion of a HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). Any method can be used to ascertain whether specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained, for example, using binding assays and conditions described in the art.[000131] In some examples, an antibody of the disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. For example, an antibody described herein may include one or more CDR sequence(s) from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb containing up to 5, 4, 3, 2, or 1 amino acid residue variations as compared to the corresponding CDR region in any one of the CDRs provided herein (e.g., CDRs from any of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb) so long as specific binding to trypsin 1 (e.g., human or non-human primate trypsin 1) and trypsin 2 (e.g., human or non-human primate trypsin 2) is maintained (e.g., substantially maintained, for example, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, any of the amino acid variations in any of the CDRs provided herein may be conservative variations. Conservative variations can be introduced into the CDRs at positions where the residues are not likely to be involved in interacting with a trypsin 1 (e.g., human or non-human primate trypsin 1) and / or a trypsin 2 (e.g., human or non-human primate trypsin 2), for example, as determined based on a crystal structure. Some aspects of the disclosure provide antibodies that comprise one or more of the heavy chain variable (VH) and / or light chain variable (VL) domains provided herein. In some embodiments, any of the VH domains provided herein include one or more of the HC CDR sequences (e.g., HC CDR1, HC CDR2, and HC CDR3) provided herein, for example, any of theHC CDR sequences provided in any one of the anti-trypsin 1 / trypsin 2 selected from Tables la and lb. In some embodiments, any of the VL domains provided herein include one or more of the LC CDR sequences (e.g., LC CDR1, LC CDR2, and LC CDR3) provided herein, for example, any of the LC CDR sequences provided in any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb.[000132] In some embodiments, an antibody of the disclosure include any antibody that includes a heavy chain variable domain and / or a light chain variable domain of any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb, and variants thereof. In some embodiments, fin antibody of the disclosure include any antibody that includes the heavy chain variable and light chain variable pairs of any anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb.[000133] Aspects of the disclosure provide antibodies having a heavy chain variable (VH) and / or a light chain variable (VL) domain amino acid sequence homologous to any of those described herein. In some embodiments, an antibody comprises a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the heavy chain variable sequence and / or any light chain variable sequence of any one of the anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb. In some embodiments, the homologous heavy chain variable and / or a light chain variable amino acid sequences do not vary within any of the CDR sequences provided herein. For example, in some embodiments, the degree of sequence variation ((e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a heavy chain variable and / or a light chain variable sequence excluding any of the CDR sequences provided herein. In some embodiments, an antibody provided herein comprise a heavy chain variable sequence and a light chain variable sequence that comprises a framework sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of any anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb.[000134] In some embodiments, an anti- trypsin 1 / trypsin 2 antibody of the present disclosure is an antibody comprising a VH containing no more than 20 amino acid variations (e.g., no morethan 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH of any of the anti- trypsin 1 / trypsin 2 antibodies listed in Tables la and lb. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure is an antibody comprising a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL, of any one of the anti-trypsin 1 / trypsin 2 antibodies listed in Tables la and lb. In some embodiments, a heavy chain variable and / or a light chain variable amino acid sequences do not vary within any of the CDR sequences provided herein. For example, in some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a heavy chain variable and / or a light chain variable sequence excluding any of the CDR sequences provided herein. In some embodiments, any of the anti-trypsin 1 / trypsin 2 antibodies provided herein comprise a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of any one of anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of any one of anti-trypsin 1 / trypsin 2 antibodies selected from Tables la and lb.[000135] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 57. Alternatively or in addition, the anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 58.[000136] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000137] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all of the three heavy chain CDRs is within the defined range. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000138] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%’, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000139] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3,2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000140] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%’, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 2; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%’, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 3.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 6.[000141] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 57. Alternatively or inaddition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 58.[000142] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 57. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 58. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 57 and / or a VL of SEQ ID NO: 58 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 57, and / or a light chain variable sequence that comprises a framework sequence that collectively contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 58.[000143] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 57. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 58. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 57, and / or a VL of SEQ ID NO: 58 excluding any of the CDR sequences therein.In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable region that comprises framework region sequences that collectively are at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the framework sequences of a VH as set forth in SEQ ID NO: 57, and / or a light chain variable region that comprises a framework region sequences that collectively are at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identical to the framework sequences of a VL as set forth in SEQ ID NO: 58.[000144] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 59. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 60.[000145] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 7, a HC CDR2 having the amino acid sequence of SEQ ID NO: 8, a HC CDR3 having the amino acid sequence of SEQ ID NO: 9, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 10.[000146] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 7, HC CDR2 having the amino acid sequence of SEQ ID NO: 8, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 10.[000147] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 7, HC CDR2 having the amino acid sequence of SEQ ID NO: 8, and HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 10.[000148] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 7; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 8; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 9. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 10.[000149] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO:7; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 8; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 9.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80%’ (e.g., at least 80%’, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 10.[000150] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 59. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 60.[000151] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 59. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 60. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 59 and / or a VL of SEQ ID NO: 60 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chainvariable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 59, and / or a light chain variable sequence that comprises a framework sequence that collectively contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 60.[000152] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 59. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 60. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%’, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 59, and / or a VL of SEQ ID NO: 60 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 59, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 60.[000153] hi some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 61. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 62.[000154] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 11, a HC CDR2 having the amino acid sequence of SEQ ID NO: 12, a HC CDR3 having the amino acid sequence of SEQ ID NO: 13, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 16.[000155] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 11, HC CDR2 having the amino acid sequence of SEQ ID NO: 12, and HC CDR3 having the amino acid sequence of SEQ ID NO: 13. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 16.[000156] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 11, HC CDR2 having the amino acid sequence of SEQ ID NO: 12, and HC CDR3 having the amino acid sequence of SEQ ID NO: 13.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 16.[000157] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 11; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 12; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 13. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 16.[000158] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%’, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 11; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%’, at least 90%, at least 91%, at least 92%’, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 12; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 13.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, atleast 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 16.[000159] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 61. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 62.[000160] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 61. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 62. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 61 and / or a VL of SEQ ID NO: 62 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 61, and / or a light chain variable sequence that comprises a framework sequence that collectively contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 62.[000161] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 61. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth inSEQ ID NO: 62. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 61, and / or a VL of SEQ ID NO: 62 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 61, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 62.[000162] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 63. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 64.[000163] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 17, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 19, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 20.[000164] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 17, HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and HC CDR3 having the amino acid sequence of SEQ ID NO: 19. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) ascompared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 20.[000165] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 17, HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and HC CDR3 having the amino acid sequence of SEQ ID NO: 19.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 20.[000166] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 17; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 18; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 19. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 20.[000167] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 17; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 18; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 19.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 that is at least 80%’ (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%’, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%’, at least 90%, at least 91%, at least 92%’, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 20.[000168] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 63. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 64.[000169] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 63. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 64. In someembodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 63 and / or a VL of SEQ ID NO: 64 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 63, and / or a light chain variable sequence that comprises a framework sequence that collectively contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 64.[000170] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 63. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 64. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 63, and / or a VL of SEQ ID NO: 64 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 63, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 64.[000171] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 65. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 66.[000172] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 23, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000173] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 21, HC CDR2 having the amino acid sequence of SEQ ID NO: 22, and HC CDR3 having the amino acid sequence of SEQ ID NO: 23. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000174] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 21, HC CDR2 having the amino acid sequence of SEQ ID NO: 22, and HC CDR3 having the amino acid sequence of SEQ ID NO: 23.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, atleast 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000175] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 21; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 22; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 23. Alternatively or in addition, the anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000176] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 21; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 22; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 23.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000177] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 65. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 66.[000178] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 65. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 66. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 65 and / or a VL of SEQ ID NO: 66 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 65, and / or a light chain variable sequence that comprises a framework sequence that collectively contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 66.[000179] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, atleast 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 65. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 66. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 65, and / or a VL of SEQ ID NO: 66 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%.’, at. least 85%, at least 90%, at least 91%, at least. 92%?, at. least 93%, at least 94%, at least 95%, at least 96%?, at. least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 65, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 66.[000180] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 67. Alternatively or in addition, the anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 68.[000181] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 25, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 26.[000182] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as comparedwith the HC CDR1 having the amino acid sequence of SEQ ID NO: 21, HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and HC CDR3 having the amino acid sequence of SEQ ID NO: 25. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 26.[000183] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 21, HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and HC CDR3 having the amino acid sequence of SEQ ID NO: 25.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%’, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%’, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 26.[000184] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 21; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 18; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 25. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 having no more than 3 amino acid variations (e.g., nomore than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 26.[000185] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 21; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 18; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 25.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 that is at least 80%’ (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 26.[000186] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 67. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 68.[000187] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared withthe VH as set forth in SEQ ID NO: 67. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 68. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 67 and / or a VL of SEQ ID NO: 68 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 67, and / or a light chain variable sequence that comprises a framework sequence that collectively contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 68.[000188] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%’, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 67. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 68. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 67, and / or a VL of SEQ ID NO: 68 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 67, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 68.[000189] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 166. Alternatively, or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 66.[000190] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 165, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000191] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 21, HC CDR2 having the amino acid sequence of SEQ ID NO: 22, and HC CDR3 having the amino acid sequence of SEQ ID NO: 165. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000192] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 21, HC CDR2 having the amino acid sequence of SEQ ID NO: 22, and HC CDR3 having the amino acid sequence of SEQ ID NO: 165.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14, LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000193] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 21; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 22; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 165. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000194] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 21; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 22; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 165.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 14; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 15; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 24.[000195] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody corresponding to the antibody “Trypsin 1 / Trypsin 2-Dual-L2-Ab5” (also referred to as “L2-Ab5”) in Table la is a variant of the anti-trypsin 1 / trypsin 2 antibody corresponding to the antibody “Trypsin 1 / Trypsin 2-Dual-L2-Ab3” (also referred to as “L2-Ab3”) in table 1a. HC CDR3 of L2-Ab5 was modified by introducing a K11R substitution with respect to HC CDR3 of L2-Ab3, corresponding to the amino acid sequence of SEQ ID NO: 23. Substitution of the lysine at amino acid position 11 of SEQ ID NO: 23 with an arginine removed the lysine glycation site, thereby reducing the acidic species in the population of the antibody being produced. Furthermore, the motif “KSIR” (SEQ ID NO: 243) in SEQ ID NO: 23 may be a target site for the enzyme furin. Changing it to “RSIR” (SEQ ID NO: 244) prevents the antibody from being cleaved by furin.[000196] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 166. Alternatively, or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 66.[000197] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 166. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 66. In someembodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 166 and / or a VL of SEQ ID NO: 66 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 166, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 66.[000198] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 166. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 66. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 166, and / or a VL of SEQ ID NO: 66 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 166, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%;, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 66.[000199] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having theamino acid sequence of SEQ ID NO: 69. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 70.[000200] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 27, a HC CDR2 having the amino acid sequence of SEQ ID NO: 28, a HC CDR3 having the amino acid sequence of SEQ ID NO: 29, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000201] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 27, HC CDR2 having the amino acid sequence of SEQ ID NO: 28, and HC CDR3 having the amino acid sequence of SEQ ID NO: 29. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 30, LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000202] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 27, HC CDR2 having the amino acid sequence of SEQ ID NO: 28, and HC CDR3 having the amino acid sequence of SEQ ID NO: 29.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LCCDR1 having the amino acid sequence of SEQ ID NO: 30, LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000203] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 27; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 28; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 29. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 30; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000204] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%’, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 27; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 28; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%?, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 29.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%?, at least 91%?, at least 92%, at least 93%, at least 94%, at least 95%?, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO:30; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000205] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 69. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 70.[000206] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 69. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 70. In some embodiments, the number of amino acid variations e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 69 and / or a VL of SEQ ID NO: 70 excluding any of the CDR sequences therein. In some embodiments, an anti -trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 69, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 70.[000207] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 69. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the presentdisclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 70. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 69, and / or a VL of SEQ ID NO: 70 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 69, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 70.[000208] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 71. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 70.[000209] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 33, a HC CDR2 having the amino acid sequence of SEQ ID NO: 34, a HC CDR3 having the amino acid sequence of SEQ ID NO: 35, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000210] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 33, HC CDR2 having the amino acid sequence of SEQ ID NO: 34, and HC CDR3 having the amino acid sequence of SEQID NO: 35. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 30, LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000211] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 33, HC CDR2 having the amino acid sequence of SEQ ID NO: 34, and HC CDR3 having the amino acid sequence of SEQ ID NO: 35.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%’, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%’, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 30, LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000212] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 33; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 34; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 35. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 30; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 having no more than 3 amino acid variations(e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000213] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 33; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 34; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 35.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 30; a LC CDR2 that is at least 80%’ (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%’, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000214] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 71. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 70.[000215] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 71. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acidvariations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 70. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 71 and / or a VL of SEQ ID NO: 70 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 71, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 70.[000216] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 71. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 70. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 71, and / or a VL of SEQ ID NO: 70 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 71, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%;, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 70.[000217] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 233. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 70.[000218] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 27, a HC CDR2 having the amino acid sequence of SEQ ID NO: 28, a HC CDR3 having the amino acid sequence of SEQ ID NO: 29, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000219] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 27, HC CDR2 having the amino acid sequence of SEQ ID NO: 28, and HC CDR3 having the amino acid sequence of SEQ ID NO: 29. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 30, LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000220] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 27, HC CDR2 having the amino acid sequence of SEQ ID NO: 28, and HC CDR3 having the amino acid sequence of SEQ ID NO: 29. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, atleast 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 30, LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000221] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 27; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 28; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 29. Alternatively or in addition, the anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 30; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000222] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 27; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 28; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 29.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 30; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 31; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 32.[000223] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 233. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 70.[000224] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 233. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 70. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 233 and / or a VL of SEQ ID NO: 70 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 233, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 70.[000225] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ IDNO: 233. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 70. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 233, and / or a VL of SEQ ID NO: 70 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 233, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 70.[000226] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 72. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 73.[000227] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 36, a HC CDR2 having the amino acid sequence of SEQ ID NO: 37, a HC CDR3 having the amino acid sequence of SEQ ID NO: 38, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000228] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 36, HC CDR2 having theamino acid sequence of SEQ ID NO: 37, and HC CDR3 having the amino acid sequence of SEQ ID NO: 38. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000229] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 36, HC CDR2 having the amino acid sequence of SEQ ID NO: 37, and HC CDR3 having the amino acid sequence of SEQ ID NO: 38.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%’, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000230] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 36; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 37; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 38. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acidsequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000231] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%;, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 36; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%?, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 37; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%?, at least 92%?, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 38.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%’, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000232] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 72. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 73.[000233] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 72. Alternatively or in addition, the anti-trypsin 1 / trypsin 2antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 73. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 72 and / or a VL of SEQ ID NO: 73 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 72, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 73.[000234] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 72. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 73. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 72, and / or a VL of SEQ ID NO: 73 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 72, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 73.[000235] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDRl, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 74. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDRl, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 73.[000236] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDRl having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 38, a LC CDRl having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000237] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDRl, a HC CDR2, and a HC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDRl having the amino acid sequence of SEQ ID NO: 40, HC CDR2 having the amino acid sequence of SEQ ID NO: 41, and HC CDR3 having the amino acid sequence of SEQ ID NO: 38. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDRl, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDRl having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000238] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDRl, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDRl having the amino acid sequence of SEQ ID NO: 40, HC CDR2 having the amino acid sequence of SEQ ID NO: 41, and HC CDR3 having the amino acid sequence of SEQ ID NO: 38.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosurecomprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000239] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR1 having the amino acid sequence of SEQ ID NO: 40; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 41; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 38. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000240] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 40; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 41; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 38.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosurecomprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000241] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 74. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 73.[000242] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 74. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 73. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 74 and / or a VL of SEQ ID NO: 73 excluding any of the CDR sequences therein, In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 74, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 73.[000243] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, atleast 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 74. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VL as set forth in SEQ ID NO: 73. In some embodiments, the degree of sequence variation (e.g., at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) may occur within a VH of SEQ ID NO: 74, and / or a VL of SEQ ID NO: 73 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprise a heavy chain variable sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VH of SEQ ID NO: 74, and / or a light chain variable sequence that comprises a framework sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical to the framework sequence of a VL of SEQ ID NO: 73.[000244] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 75. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 73.[000245] In some embodiments, an anti -trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000246] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3, which collectively contains no more than5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variation) as compared with the HC CDRl having the amino acid sequence of SEQ ID NO: 40, HC CDR2 having the amino acid sequence of SEQ ID NO: 41, and HC CDR3 having the amino acid sequence of SEQ ID NO: 42. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3, which collectively contains no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2 or 1 amino acid variation) as compared with the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000247] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 40, HC CDR2 having the amino acid sequence of SEQ ID NO: 41, and HC CDR3 having the amino acid sequence of SEQ ID NO: 42.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a LC CDRl, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%’, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000248] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDRl having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDRl having the amino acid sequence of SEQ ID NO: 40; a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR2 having the amino acid sequence of SEQ ID NO: 41; and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the HC CDR3 having the amino acid sequence of SEQ ID NO: 42. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDRl having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDRl having the amino acidsequence of SEQ ID NO: 4; a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variation) as compared with the LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000249] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 40; a HC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR2 having the amino acid sequence SEQ ID NO: 41; and / or a HC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 42.Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%,, at least 98%, or at least 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 39.[000250] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 75. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 73.[000251] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18,17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VH as set forth in SEQ ID NO: 75. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) as compared with the VL as set forth in SEQ ID NO: 73. In some embodiments, the number of amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) may occur within a VH of SEQ ID NO: 75 and / or a VL of SEQ ID NO: 73 excluding any of the CDR sequences therein. In some embodiments, an anti-trypsin 1 / trypsin 2 antibody provided herein comprises a heavy chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VH of SEQ ID NO: 75, and / or a light chain variable sequence that comprises a framework sequence that contains no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation to the framework sequence of a VL of SEQ ID NO: 73.[000252] In some embodiments, an anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VH comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99%) identical to the VH as set forth in SEQ ID NO: 75. Alternatively or in addition, the anti-trypsin 1 / trypsin 2 antibody of the present disclosure comprises a VL comprising an amino acid sequence that is at least 80% (e.g., at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, ...

Claims

CLAIMSWhat is claimed is:

1. A dual inhibitor antibody that specifically binds to trypsin 1 and trypsin 2, the dual inhibitor antibody comprising:(a) a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), HC CDR2, and HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 57, and a light chain (LC) complementarity determining region (CDR) 1 (LC CDR1), LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 58;(b) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 59, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 60;(c) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 61, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 62;(d) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 63, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 64;(e) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 65, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 66;(f) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 67, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 68;(g) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 166, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 66;(h) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 69, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70;(i) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 71, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70;(j) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 72, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73;(k) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 74, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73;(l) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 75, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73;(m) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 76, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73;(n) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 77, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 78;(o) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 79, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 80;(p) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 81, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 82;(q) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 203, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204;(r) a HC CDRl, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 217, and a LC CDRl, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204;(s) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 83, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70;(t) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 84, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70;(u) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 233, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 70; or(v) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 237, and a LC CDR1, LC CDR2, and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 73; anda heavy chain constant region that comprises:one or more substitutions that reduce effector function; andone or more substitutions that extend serum half-life.

2. The dual inhibitor antibody of claim 1, wherein the one or more substitutions that reduce effector function are substitutions at L234, L235, and / or P329 according to the EU numbering.

3. The dual inhibitor antibody of claim 1 or 2, wherein the one or more substitutions that reduce effector function are L234A, L235A, and / or P329A according to the EU numbering.

4. The dual inhibitor antibody of any one of claims 1 to 3, wherein the heavy chain constant region comprises L234A, L235A, and P329A substitutions according to the EU numbering.

5. The dual inhibitor antibody of any one of claims 1 to 4, wherein the one or more substitutions that extend serum half-life are substitutions at M428, N434S, M252, S254, and / or T256 according to the EU numbering.

6. The dual inhibitor antibody of any one of claims 1 to 5, wherein the one or more substitutions that extend serum half-life are M428L, N434S, M252Y, S254T, and / orT256E according to the EU numbering.

7. The dual inhibitor antibody of any one of claims 1 to 5, wherein the one or more substitutions that extend serum half-life are M428L, N434A, M252Y, S254T, and / or T256E according to the EU numbering.

8. The dual inhibitor antibody of any one of claims 1 to 7, wherein the heavy chain constant region comprises:(i) M428L and N434A according to the EU numbering;(ii) M428L and N434S according to the EU numbering; or(iii) M252Y, S254T, and T256E according to the EU numbering.

9. The dual inhibitor antibody of any one of claims 1 to 8, wherein the heavy chain constant region comprises L234A, L235 A, P329A, M428L and N434A substitutions according to the EU numbering.

10. The dual inhibitor antibody of any one of claims 1 to 9, wherein the heavy chain constant regions comprises the amino acid sequence of SEQ ID NO: 229.

11. The dual inhibitor antibody of any one of claims 1 to 8, wherein the heavy chain constant region comprises L234A, L235A, P329A, M428L and N434S substitutions according to the EU numbering.

12. The dual inhibitor antibody of any one of claims 1 to 8 or 11, wherein the heavy chain constant regions comprises the amino acid sequence of SEQ ID NO: 230.

13. The dual inhibitor antibody of any one of claims 1 to 8, wherein the heavy chain constant region comprises L234A, L235A, P329A, M252Y, S254T, and T256E substitutions according to the EU numbering.

14. The dual inhibitor antibody of any one of claims 1 to 8 or 13, wherein the heavy chain constant regions comprises the amino acid sequence of SEQ ID NO: 231.

15. The dual inhibitor antibody of any one of claims 1 to 14, wherein the dual inhibitor antibody comprises:(a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6;(b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 7, a HC CDR2 having the amino acid sequence of SEQ ID NO: 8, a HC CDR3 having the amino acid sequence of SEQ ID NO: 9, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 10;(c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 11, a HC CDR2 having the amino acid sequence of SEQ ID NO: 12, a HC CDR3 having the amino acid sequence of SEQ ID NO: 13, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 16;(d) a HC CDR1 having the amino acid sequence of SEQ ID NO: 17, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 19, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 20;(e) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 23, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24;(f) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 25, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 26;(g) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 165, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24;(h) a HC CDR1 having the amino acid sequence of SEQ ID NO: 27, a HC CDR2 having the amino acid sequence of SEQ ID NO: 28, a HC CDR3 having the amino acid sequence of SEQ ID NO: 29, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32;(i) a HC CDR1 having the amino acid sequence of SEQ ID NO: 33, a HC CDR2 having the amino acid sequence of SEQ ID NO: 34, a HC CDR3 having the amino acid sequence of SEQ ID NO: 35, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32;(j) a HC CDR1 having the amino acid sequence of SEQ ID NO: 36, a HC CDR2 having the amino acid sequence of SEQ ID NO: 37, a HC CDR3 having the amino acid sequence of SEQ ID NO: 38, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39;(k) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 38, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39;(l) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39;(m) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 43, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 39;(n) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 41, a HC CDR3 having the amino acid sequence of SEQ ID NO: 44, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 45;( o) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 46, a HC CDR3 having the amino acid sequence of SEQ ID NO: 47, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48;(p) a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 having the amino acid sequence of SEQ ID NO: 50, a HC CDR3 having the amino acid sequence of SEQ ID NO: 51, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 52;(q) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 202, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48;(r) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 216, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48;(s) a HC CDR1 having the amino acid sequence of SEQ ID NO: 27, a HC CDR2 having the amino acid sequence of SEQ ID NO: 28, a HC CDR3 having the amino acid sequence of SEQ ID NO: 53, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32; or(t) a HC CDR1 having the amino acid sequence of SEQ ID NO: 54, a HC CDR2 having the amino acid sequence of SEQ ID NO: 55, a HC CDR3 having the amino acid sequence of SEQ ID NO: 56, a LC CDR1 having the amino acid sequence of SEQ ID NO: 30, a LC CDR2 having the amino acid sequence of SEQ ID NO: 31, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 32.

16. The dual inhibitor antibody of any one of claims 1 to 15, wherein the dual inhibitor antibody comprises:(a) a VH comprising the amino acid sequence of SEQ ID NO: 57, and a VL comprising the amino acid sequence of SEQ ID NO: 58;(b) a VH comprising the amino acid sequence of SEQ ID NO: 59, and a VL comprising the amino acid sequence of SEQ ID NO: 60;(c) a VH comprising the amino acid sequence of SEQ ID NO: 61, and a VL comprising the amino acid sequence of SEQ ID NO: 62;(d) a VH comprising the amino acid sequence of SEQ ID NO: 63, and a VL comprising the amino acid sequence of SEQ ID NO: 64;(e) a VH comprising the amino acid sequence of SEQ ID NO: 65, and a VL comprising the amino acid sequence of SEQ ID NO: 66;(f) a VH comprising the amino acid sequence of SEQ ID NO: 67, and a VL comprising the amino acid sequence of SEQ ID NO: 68;(g) a VH comprising the amino acid sequence of SEQ ID NO: 166, and a VL comprising the amino acid sequence of SEQ ID NO: 66;(h) a VH comprising the amino acid sequence of SEQ ID NO: 69, and a VL comprising the amino acid sequence of SEQ ID NO: 70;(i) a VH comprising the amino acid sequence of SEQ ID NO: 71, and a VL comprising the amino acid sequence of SEQ ID NO: 70;(j) a VH comprising the amino acid sequence of SEQ ID NO: 72, and a VL comprising the amino acid sequence of SEQ ID NO: 73;(k) a VH comprising the amino acid sequence of SEQ ID NO: 74, and a VL comprising the amino acid sequence of SEQ ID NO: 73;(l) a VH comprising the amino acid sequence of SEQ ID NO: 75, and a VL comprising the amino acid sequence of SEQ ID NO: 73;(m) a VH comprising the amino acid sequence of SEQ ID NO: 76, and a VL comprising the amino acid sequence of SEQ ID NO: 73;(n) a VH comprising the amino acid sequence of SEQ ID NO: 77, and a VL comprising the amino acid sequence of SEQ ID NO: 78;(o) a VH comprising the amino acid sequence of SEQ ID NO: 79, and a VL comprising the amino acid sequence of SEQ ID NO: 80;(p) a VH comprising the amino acid sequence of SEQ ID NO: 81, and a VL comprising the amino acid sequence of SEQ ID NO: 82;(q) a VH comprising the amino acid sequence of SEQ ID NO: 203, and a VL comprising the amino acid sequence of SEQ ID NO: 204;(r) a VH comprising the amino acid sequence of SEQ ID NO: 217, and a VL comprising the amino acid sequence of SEQ ID NO: 204;(s) a VH comprising the amino acid sequence of SEQ ID NO: 83, and a VL comprising the amino acid sequence of SEQ ID NO: 70;(t) a VH comprising the amino acid sequence of SEQ ID NO: 84, and a VL comprising the amino acid sequence of SEQ ID NO: 70;(u) a VH comprising the amino acid sequence of SEQ ID NO: 223, and a VL comprising the amino acid sequence of SEQ ID NO: 70; or(v) a VH comprising the amino acid sequence of SEQ ID NO: 237, and a VL comprising the amino acid sequence of SEQ ID NO: 73.

17. The dual inhibitor antibody of any one of claims 1 to 16, wherein the dual inhibitor antibody further comprises a light chain constant region.

18. The dual inhibitor antibody of claim 17, wherein the light chain constant region comprises the amino acid sequence of SEQ ID NO: 232.

19. A dual inhibitor antibody that specifically binds trypsin 1 and trypsin 2, the dual inhibitor antibody comprising:(a) a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), a HC CDR2, a HC CDR3, a light chain (LC) complementarity determining region (CDR) 1 (LC CDRl), a LC CDR2, and / or a LC CDR3 of any one of the antibodies listed in Table la and Table lb; or(b) a heavy chain variable domain (VH) and / or a light chain variable domain (VL) of any one of the antibodies listed in Table la; anda heavy chain constant region comprising a L234A, L235A, and P329A substitution according to the EU numbering, and:(i) M428L and N434A substitutions according to the EU numbering;(ii) M428L and N434S substitutions according to the EU numbering; or(iii) M252Y, S254T, and T256E substitutions according to the EU numbering.

20. The dual inhibitor antibody of any one of claims 1 to 19 comprising:(a) a heavy chain (HC) comprising the amino acid sequence of any one of SEQ ID NOs: 141-143; and a light chain (LC) comprising the amino acid sequence of SEQ ID NO: 144;(b) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 145-147; and a LC comprising the amino acid sequence of SEQ ID NO: 148;(c) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 149-151; and a LC comprising the amino acid sequence of SEQ ID NO: 152;(d) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 153-155; and a LC comprising the amino acid sequence of SEQ ID NO: 156;(e) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 157-159; and a LC comprising the amino acid sequence of SEQ ID NO: 160;(f) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 161-163; and a LC comprising the amino acid sequence of SEQ ID NO: 164;(g) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 167-169; and a LC comprising the amino acid sequence of SEQ ID NO: 160;(h) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 170-172; and a LC comprising the amino acid sequence of SEQ ID NO: 173;(i) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 174-176; and a LC comprising the amino acid sequence of SEQ ID NO: 173;(j) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 177-179; and a LC comprising the amino acid sequence of SEQ ID NO: 180;(k) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 181-183; and a LC comprising the amino acid sequence of SEQ ID NO: 180;(l) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 184-186; and a LC comprising the amino acid sequence of SEQ ID NO: 180;(m) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 187-189; and a LC comprising the amino acid sequence of SEQ ID NO: 180;(n) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 190-192; and a LC comprising the amino acid sequence of SEQ ID NO: 193;(o) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 194-196; and a LC comprising the amino acid sequence of SEQ ID NO: 197;(p) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 198-200; and a LC comprising the amino acid sequence of SEQ ID NO: 201;(q) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 205-207; and a LC comprising the amino acid sequence of SEQ ID NO: 208;(r) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 218-220; and a LC comprising the amino acid sequence of SEQ ID NO: 208;(s) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 209-212; and a LC comprising the amino acid sequence of SEQ ID NO: 173;(t) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 213-215; and a LC comprising the amino acid sequence of SEQ ID NO: 173;(u) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 234-236; and a LC comprising the amino acid sequence of SEQ ID NO: 173; or(v) a HC comprising the amino acid sequence of any one of SEQ ID NOs: 238-240; and a LC comprising the amino acid sequence of SEQ ID NO: 173.

21. The dual inhibitor antibody of any one of claims 1 to 20, wherein the dual inhibitor antibody binds to the active site of trypsin 1 and the active site of trypsin 2.

22. The dual inhibitor antibody of any one of claims 1 to 21, wherein the dual inhibitor antibody binds to an active form of trypsin 1 and an active form of trypsin 2 but does not bind to an inactive form of trypsin 1 or the inactive form of trypsin 2.

23. The dual inhibitor antibody of any one of claims 1 to 22, wherein the dual inhibitor antibody inhibits protease activity of trypsin 1 and / or trypsin 2.

24. The dual inhibitor antibody of any one of claims 1 to 23, wherein the dual inhibitor antibody is not cleaved in the heavy chain by trypsin 1 and / or trypsin 2 on binding to trypsin 1 and trypsin 2.

25. The dual inhibitor antibody of any one of claims 1 to 24, wherein the dual inhibitor antibody is cleaved in the heavy chain by trypsin 1 and / or trypsin 2 on binding to trypsin 1 and / or trypsin 2 but remains bound to trypsin 1 and trypsin 2.

26. The dual inhibitor antibody of claim 25, wherein the dual inhibitor antibody inhibits protease activity of trypsin 1 and / or trypsin 2 after being cleaved in the heavy chain by trypsin 1 and / or trypsin 2 on binding to trypsin 1 and trypsin 2.

27. A dual inhibitor antibody that specifically binds trypsin 1 and trypsin 2, the dual inhibitor antibody comprising:(a) a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), a HC CDR2, and a HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 166, and a light chain (LC) complementarity determining region (CDR) 1 (LC CDR1), LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 66;(b) a HC CDR1, HC CDR2, and HC CDR3 of a VH having the amino acid sequence of SEQ ID NO: 203, and a LC CDR1, LC CDR2,and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204; or(c) a HC CDR1, HC CDR2 and HC CDR 3 of a VH having the amino acid sequence of SEQ ID NO: 217, and a LC CDR1, LC CDR2 and LC CDR3 of a VL having the amino acid sequence of SEQ ID NO: 204.

28. The dual inhibitor antibody of claim 27, wherein the dual inhibitor antibody comprises:(a) a HC CDR1 having the amino acid sequence of SEQ ID NO: 21, a HC CDR2 having the amino acid sequence of SEQ ID NO: 22, a HC CDR3 having the amino acid sequence of SEQ ID NO: 165, a LC CDR1 having the amino acid sequence of SEQ ID NO: 14, a LC CDR2 having the amino acid sequence of SEQ ID NO: 15, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24;(b) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 202, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48; or(c) a HC CDR1 having the amino acid sequence of SEQ ID NO: 40, a HC CDR2 having the amino acid sequence of SEQ ID NO: 216, a HC CDR3 having the amino acid sequence of SEQ ID NO: 42, a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 48.

29. The dual inhibitor antibody of claim 27 or 28, wherein the dual inhibitor antibody comprises:(a) a VH comprising the amino acid sequence of SEQ ID NO: 166, and a VL comprising the amino acid sequence of SEQ ID NO: 66;(b) a VH comprising the amino acid sequence of SEQ ID NO: 203, and a VL comprising the amino acid sequence of SEQ ID NO: 204; or(c) a VH comprising the amino acid sequence of SEQ ID NO: 217, and a VL comprising the amino acid sequence of SEQ ID NO: 204.

30. The dual inhibitor antibody of any one of claims 27 to 29, further comprising a heavy chain constant region that comprises:one or more substitutions that reduce effector function; andone or more substitutions that extend serum half-life.

31. An isolated nucleic acid comprising a nucleic acid sequence encoding the VH and / or the VL, or the HC and / or the LC of the dual inhibitor antibody of any one of claims 1 to 30.

32. The isolated nucleic acid of claim 31, wherein the isolated nucleic acid comprises:(a) a nucleic acid sequence of SEQ ID NO: 105, and / or a nucleic acid sequence of SEQ ID NO: 106;(b) a nucleic acid sequence of SEQ ID NO: 107, and / or a nucleic acid sequence of SEQ ID NO: 108;(c) a nucleic acid sequence of SEQ ID NO: 109, and / or a nucleic acid sequence of SEQ ID NO: 110;(d) a nucleic acid sequence of SEQ ID NO: 111, and / or a nucleic acid sequence of SEQ ID NO: 112;(e) a nucleic acid sequence of SEQ ID NO: 113, and / or a nucleic acid sequence of SEQ ID NO: 114;(f) a nucleic acid sequence of SEQ ID NO: 115, and / or a nucleic acid sequence of SEQ ID NO: 116;(g) a nucleic acid sequence of SEQ ID NO: 221, and / or a nucleic acid sequence of SEQ ID NO: 222;(h) a nucleic acid sequence of SEQ ID NO: 117, and / or a nucleic acid sequence of SEQ ID NO: 118;(i) a nucleic acid sequence of SEQ ID NO: 119, and / or a nucleic acid sequence of SEQ ID NO: 120;(j) a nucleic acid sequence of SEQ ID NO: 121, and / or a nucleic acid sequence of SEQ ID NO: 122;(k) a nucleic acid sequence of SEQ ID NO: 123, and / or a nucleic acid sequence of SEQ ID NO: 124;(l) a nucleic acid sequence of SEQ ID NO: 125, and / or a nucleic acid sequence of SEQ ID NO: 126;(m) a nucleic acid sequence of SEQ ID NO: 127, and / or a nucleic acid sequence of SEQ ID NO: 128;(n) a nucleic acid sequence of SEQ ID NO: 129, and / or a nucleic acid sequence of SEQ ID NO: 130;(o) a nucleic acid sequence of SEQ ID NO: 131, and / or a nucleic acid sequence of SEQ ID NO: 132;(p) a nucleic acid sequence of SEQ ID NO: 133, and / or a nucleic acid sequence of SEQ ID NO: 134;(q) a nucleic acid sequence of SEQ ID NO: 223, and / or a nucleic acid sequence of SEQ ID NO: 224;(r) a nucleic acid sequence of SEQ ID NO: 225 and / or a nucleic acid sequence of SEQ ID NO: 226;(s) a nucleic acid sequence of SEQ ID NO: 135, and / or a nucleic acid sequence of SEQ ID NO: 136; or(t) a nucleic acid sequence of SEQ ID NO: 137, and / or a nucleic acid sequence of SEQ ID NO: 138.

33. An expression vector comprising the isolated nucleic acid of claim 31 or 3234. A host cell comprising the dual inhibitor antibody of any one of claims 1 to 30, the isolated nucleic acid of claim 31 or 32, or the expression vector of claim 33.

35. The host cell of claim 34, wherein the host cell is a CHO cell, or a HEK293 cell.

36. A method for producing the dual inhibitor antibody of any one of claims 1 to 30, the method comprising:(i) culturing the host cell of claim 34 or 35 under conditions for expressing the dual inhibitor antibody; and(ii) harvesting the dual inhibitor antibody from a host cell lysate or culture supernatant.

37. The method of claim 36, further comprising purifying the dual inhibitor antibody.

38. A composition comprising the dual inhibitor antibody of any one of claims 1 to 30, the isolated nucleic acid of claim 31 or 32, the expression vector of claim 33, or the host cell of claim 34 or 35.

39. The composition of claim 38, further comprising a pharmaceutically acceptable carrier.

40. A method of treating pancreatitis, the method comprising administering to a subject in need thereof an effective amount of a dual inhibitor antibody of any one of claims 1 to 30, the isolated nucleic acid of claim 31 or 32, the expression vector of claim 33, the host cell of claim 34 or 35, or the composition of claim 38 or 39.

41. The method of claim 40, wherein the subject has hereditary pancreatitis, acute pancreatitis, recurrent acute pancreatitis, or chronic pancreatitis.

42. A method of treating pancreatitis, the method comprising administering to a subject in need thereof an effective amount of at least one antibody that specifically binds to trypsin 1 and / or trypsin 2.

43. The method of claim 42, wherein the at least one antibody specifically binds to trypsin 1.

44. The method of claim 42 or 43, wherein the at least one antibody specifically binds to the active site of trypsin 1.

45. The method of any one of claims 42 to 44, wherein the at least one antibody inhibits protease activity of trypsin 1.

46. The method of claim 42, wherein the at least one antibody specifically binds to trypsin47. The method of claim 42 or 46, wherein the at least one antibody specifically binds to the active site of trypsin 2.

48. The method of any one of claims 42, 46, or 47, wherein the at least one antibody inhibits protease activity of trypsin 2.

49. The method of claim 42, further comprising administering to the subject at least one antibody that specifically binds to trypsin 1 and trypsin 2 and inhibits their respective protease activities.

50. The method of claim 49, wherein the at least one antibody is a dual inhibitor antibody that specifically binds to trypsin 1 and trypsin 2.

51. The method of any one of claims 42 to 50, wherein the subject has hereditary pancreatitis, acute pancreatitis, recurrent acute pancreatitis, or chronic pancreatitis.

52. A method for treating hereditary pancreatitis (HP), the method comprising administering to a subject having (HP) an amount of an anti-trypsin 1 / trypsin 2 antibody effective for inhibitingtrypsin 1 and / or trypsin 2 protease activity, regardless of if the subject is having a flare-up episode.

53. The method of any one of claims 40 to 52, wherein the administration reduces pancreas tissue damage.

54. The method of any one of claims 40 to 53, wherein the administration reduces pancreas cell death.

55. The method of any one of claims 40 to 54, wherein the administration reduces pancreas edema.

56. A polypeptide comprising a sequence as set forth in SEQ ID NO: 103 or a fragment thereof suitable for generating an antibody that specifically binds to and inhibits protease activity of trypsin 1, optionally wherein the polypeptide comprises a tag, such as a His-tag.

57. A polypeptide comprising a sequence as set forth in SEQ ID NO: 104 or a fragment thereof suitable for generating an antibody that specifically binds to and inhibits protease activity of trypsin 2, optionally wherein the polypeptide comprises a tag, such as a His-tag.

58. A method of obtaining a dual inhibitor anti-trypsin 1 / trypsin 2 antibody, the method comprising:generating an antibody that (i) specifically binds to the polypeptide of claim 46 and inhibits protease activity of trypsin 1; and (ii) specifically binds to the polypeptide of claim 47 and inhibits protease activity of trypsin 2,thereby obtaining a dual inhibitor anti-trypsin 1 / trypsin 2 antibody.

59. An engineered non-human organism comprising in its genome an engineered nucleic acid encoding a human trypsin 1 protein that is operably linked to an endogenous promoter of the non-human organism.

60. The engineered non-human organism of claim 59, wherein the endogenous promoter is a promoter of a homolog of the human PRSS1 gene in the non-human organism.

61. The engineered non-human organism of claim 59, wherein the engineered non-human organism is a mouse.

62. The engineered non-human organism of claim 61, wherein the homolog is a mouse cationic trypsinogen T7 gene.

63. The engineered non-human organism of any one of claims 59 to 62, wherein the human trypsin 1 protein comprises an amino acid substitution associated with hereditary pancreatitis.

64. The engineered non-human organism of claim 63, wherein the amino acid substitution is R122H.

65. The engineered non-human organism of any one of claims 59 to 64, wherein the engineered nucleic acid encoding the human trypsin 1 protein comprises the nucleic acid sequence set forth in SEQ ID NO: 227.

66. A method of selecting an antibody that specifically binds to trypsin 1 and / or trypsin 2, the method comprising:(i) generating a set of antibodies that specifically binds trypsin 1 and / or trypsin 2; (ii) selecting an antibody that comprises a heavy chain complementarity determining region 3 (HC CDR3) in the range of 16-22 amino acid residues in length from the set of antibodies generated in step (i); and(iii) determining that the HC CDR3 of the selected antibody forms a loop that fits into an active site of trypsin 1 and / or trypsin 2.

67. A method of selecting an antibody that specifically binds to trypsin 1 and / or trypsin 2, the method comprising:(i) selecting an antibody that comprises a HC CDR3 in the range of 16-22 amino acid residues in length from a set of antibodies identified as specifically binding to trypsin 1 and / or trypsin 2 enzyme; and(ii) determining that the HC CDR3 of the selected antibody forms a loop that fits into an active site of trypsin 1 and / or trypsin 2.

68. The method of claim 66 or 67, wherein the determining of step (ii) is performed by modeling the three-dimensional structure of the antibody.

69. The method of any one of claims 66 to 68, wherein the HC CDR3 of the selected antibody is in the range of 19-20 amino acid residues in length.

70. The method of any one of claims 66 to 69, wherein, in the set of antibodies, the HC CDR3s comprise, on average, fewer than 16 amino acids.

71. The method of any one of claims 66 to 70, wherein the CDRs of the antibodies are determined by Kabat, Chothia, or IMGT.

72. An antibody selected from the method of any one of claims 66 to 71.

73. An antibody that specifically binds trypsin 1 and / or trypsin 2, wherein the antibody comprises a heavy chain variable domain (VH) comprising a heavy chain (HC) complementarity determining region (CDR) 1 (HC CDR1), a HC CDR2, and a HC CDR3, wherein the HC CDR3 comprises 16-22 amino acids residues forming a loop that fits into an active site of trypsin 1 and / or trypsin 2.

Images