Antibodies specifically recognizing cd40 and uses thereof

Abstract

Provided are antibodies or antigen-binding fragments that specifically recognize CD40, methods of making and uses thereof.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to Chinese Patent Application No. 202110724449.2, filed on June 29, 2021, entitled "Antibody that specifically recognizes CD40 and its application", the entire contents of which are incorporated herein by reference.

[0003] Submitting sequence lists as ASCII text files

[0004] The contents of the following submitted ASCII TEXT text file are incorporated herein by reference in their entirety: Sequence List in Computer-Readable Form (CRF) (Text name: CN_202106116475_SEQLIST.txt, Record date: 2021.06.11, Size: 139KB). Technical Field

[0005] This application provides an antibody that specifically recognizes CD40, as well as its preparation method and uses. Background Technology

[0006] CD40 is a co-stimulatory member of the tumor necrosis factor receptor (TNFR) superfamily (Croft, Michael et al. Nature reviews. Drug discovery vol. 12, 2(2013): 147-68). The function of CD40 was first identified in human B lymphocytes, where it is constitutively expressed, and CD40 signaling promotes B cell activation and proliferation (Clark, E.A., and J.A. Ledbetter. Proceedings of the National Academy of Sciences of the United States of America vol. 83, 12(1986): 4494-8). CD40 is known to be expressed on other hematopoietic cells (e.g., monocytes and dendritic cells (DCs)) to promote cell survival and cytokine production (Stout, RD, and J. Suttles. Immunology today vol. 17, 10(1996): 487-92), and can also signal to induce CD40L expression in CD4+ cells. +T cell activation, proliferation, and cytokine production (Grewal, IS, and R A Flavell. Immunology Today vol. 17, 9 (1996): 410-4). CD40 signaling can also affect the cellular responses of non-hematopoietic cells, including endothelial cells, epithelial cells, fibroblasts, and neurons (Hollenbaugh, D et al. The Journal of Experimental Medicine vol. 182, 1 (1995): 33-40; Karmann, K et al. Proceedings of the National Academy of Sciences of the United States of America vol. 92, 10 (1995): 4342-6; and Tan, Jun et al. The EMBO Journal vol. 21, 4 (2002): 643-52).

[0007] CD40L was first developed using activated CD4. + CD40 has been identified on the surface of T cells (Hollenbaugh, D et al. The EMBO journal vol. 11, 12 (1992): 4313-21), and the CD40-CD40L interaction between B and T cells has shown to be crucial in germinal center (GC) responses and in response to T-dependent antigen allotype switching (Kawabe, T et al. Immunity vol. 1, 3 (1994): 167-78). Furthermore, CD40L has been shown to be expressed in a variety of cell types, including mast cells, basophils, B cells, natural killer (NK) cells, macrophages, megakaryocytes, and platelets, highlighting the broad role of the CD40 pathway in cell biology. U, and P Libby. Cellular and molecular life sciences: CMLS vol. 58, 1 (2001): 4-43; and van Kooten, C, and J Banchereau. Journal of leukocyte biology vol. 67, 1 (2000): 2-17).

[0008] In numerous animal models, the CD40L / CD40 interaction has been demonstrated to be associated with many diseases, including systemic lupus erythematosus (Davidson, Anne et al. Annals of the New York Academy of Sciences vol. 987 (2003): 188-98), experimental allergic encephalomyelitis (Toubi, Elias, and Yehuda Shoeenfeld. Autoimmunity vol. 37, 6-7 (2004): 457-64), collagen-induced arthritis (Durie, FH et al. Science (New York, NY) vol. 261, 5126 (1993): 1328-30), immune rejection (Goldwater, R et al. American journal of transplantation vol. 13, 4 (2013): 1040-1046), and atherosclerosis-mediated cardiovascular disease (Jansen, Matthijs F et al. Basic research in...). Cardiology vol. 111, 4(2016): 38), Sjögren's syndrome (Okimura, K et al. American journal of transplantation vol. 14, 6(2014): 1290-9), systemic sclerosis (Boleto, (Et. Frontiers in immunology vol.9 2998.18 Dec.2018), immune thrombocytopenic purpura (Kuwana, Masataka et al. Blood vol.103,4(2004):1229-36), inflammatory bowel disease (Senhaji, Nezha et al. Frontiers in immunology vol.6 529.16 Oct.2015), diabetes (Balasa, B et al. Journal of immunology (Baltimore, Md.:1950) vol.159,9(1997):4620-7), RA (Gotoh, Haruhiko et al. The Journal of rheumatology vol.31,8(2004):1506-12), and cancer (Li, Rui et al. Molecular biology reports) vol. 39, 9 (2012): 8741-7; and Li, Rui et al. Immunology letters vol. 131, 2 (2010): 120-5).

[0009] Therefore, neutralizing the binding of CD40 and CD40L could be a method for treating diseases and symptoms mediated by the CD40 / CD40L pathway. Patent application WO200563981A1 discloses the anti-human CD40 antibody ASKP1240 (used as a control antibody in the examples section of this application); WO201265950A1 discloses the anti-human CD40 antibody CFZ533 (used as a control antibody in the examples section of this application).

[0010] All publications, patents, patent applications, and disclosed information in published patent applications mentioned herein are incorporated herein by reference in their entirety.

[0011] Application Overview

[0012] In some embodiments, an isolated anti-CD40 antibody is provided, comprising a heavy chain variable domain (V... H ), the V HIncludes: a heavy chain complementarity determination region (HC-CDR)1 containing GYYWS (SEQ ID NO:1); HC-CDR2 containing X1IGGSSX2X3TX4YNPSLKS (SEQ ID NO:114), where X1 is A or F, X2 is G or S, X3 is S or T, and X4 is G or N; and HC-CDR3 containing QPX1X2X3RSX4FX5Y (SEQ ID NO:116), where X1 is A, N, or Q, X2 is A, F, Q, V, W, or Y, X3 is A or Y, X4 is A, G, P, Q, or S, and X5 is A, F, H, K, Q, V, or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes KSSQSLLYX1X2NX3KNYLA (SEQ ID NO:118), wherein X1 is R, S or O, X2 is G, L, M, S, V or Y, and X3 is G, N or O; LC-CDR2, which includes WASTRES (SEQ ID NO:77); and LC-CDR3, which includes X1QYX2X3X4PT (SEQ ID NO:120), wherein X1 is A, G, M, Q or S, X2 is L, W or Y, X3 is A, G, H, S or V, and X4 is A, F, H, K, L, R, S, T, W or Y.

[0013] In some embodiments, an isolated anti-CD40 antibody is provided, which comprises V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:5-9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:29-47 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-62 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:77 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:82-101 or variants thereof, the variants comprising substitutions of up to about 3 amino acids.

[0014] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:122-143 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:169-196 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0015] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:122. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:169. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:123. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:170. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:127. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:177. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V H It contains V as shown in the amino acid sequence SEQ ID NO:129. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:179. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (v)V HIt contains V as shown in the amino acid sequence SEQ ID NO:131. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:182. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vi)V H It contains V as shown in the amino acid sequence SEQ ID NO:123. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:187. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vii)V H It contains V as shown in the amino acid sequence SEQ ID NO:135. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:189. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (viii)V H It contains V as shown in the amino acid sequence SEQ ID NO:136. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:190. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (ix)V H It contains V as shown in the amino acid sequence SEQ ID NO:137. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:191. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; or (x)V H It contains V as shown in the amino acid sequence SEQ ID NO:143. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:196. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0016] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:29, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:82, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:33, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:87, or the V L (iii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:33, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V LContains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:57; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:89, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; (iv) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:36, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:58; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:92, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (v)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:29, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:60; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:97, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vi)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:40, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The VL Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:93, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:40, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:98, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (viii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:41, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:97, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (ix)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:47, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:58; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:101, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0017] In some embodiments, any of the isolated anti-CD40 antibodies described above, the isolated anti-CD40 antibody comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:122-143 or variants thereof, wherein the variants have at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:122-143; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:169-196 or variants thereof, wherein the variants have at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:169-196.

[0018] In some embodiments, an isolated anti-CD40 antibody comprises: (i) V H It comprises the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:122; and V L It contains the amino acid sequence SEQ ID NO:169 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:169; (ii) V H It comprises the amino acid sequence SEQ ID NO:123 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:123; and V L It contains the amino acid sequence SEQ ID NO:170 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:170; (iii) V H It comprises the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:127; and V L It contains the amino acid sequence SEQ ID NO:177 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:177; (iv) V HIt comprises the amino acid sequence SEQ ID NO:129 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:129; and V L It contains the amino acid sequence SEQ ID NO:179 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:179; (v)V H It comprises the amino acid sequence SEQ ID NO:131 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:131; and V L It contains the amino acid sequence SEQ ID NO:182 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:182; (vi)V H It comprises the amino acid sequence SEQ ID NO:123 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:123; and V L It contains the amino acid sequence SEQ ID NO:187 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:187; (vii)V H It comprises the amino acid sequence SEQ ID NO:135 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:135; and V L It contains the amino acid sequence SEQ ID NO:189 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:189; (viii)V H It comprises the amino acid sequence SEQ ID NO:136 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:136; and V L It contains the amino acid sequence SEQ ID NO:190 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:190; (ix)V H It comprises the amino acid sequence SEQ ID NO:137 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:137; and V L It contains the amino acid sequence SEQ ID NO:191 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:191; or (x)V HIt comprises the amino acid sequence SEQ ID NO:143 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:143; and V L It contains the amino acid sequence SEQ ID NO:196 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:196.

[0019] In some embodiments, an isolated anti-CD40 antibody is provided, comprising a heavy chain variable domain (V... H ), the V H Includes: a heavy chain complementarity determination region (HC-CDR)1 containing RYAMH (SEQ ID NO:2); HC-CDR2 containing X1IWFDGX2X3X4YYADSVKD (SEQ ID NO:115), wherein X1 is A or G, X2 is G, N or R, X3 is A, G, K, M, Q or S, and X4 is A, D, E, K, M, N, Q, R, S or V; and HC-CDR3 containing DYDX1GX2SX3YFDY (SEQ ID NO:117), wherein X1 is A or S, X2 is W or Y, and X3 is F or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQX1IX2X3X4LX5 (SEQ ID NO:119), wherein X1 is G, I, R or Y, X2 is S or T, X3 is G, L, M or S, X4 is W or Y, and X5 is A or S; LC-CDR2, which includes YASNLES (SEQ ID NO:78); and LC-CDR3, which includes QQX1KX2YPLT (SEQ ID NO:121), wherein X1 is A, H, S or V, and X2 is K, L, M, R, S or T.

[0020] In some embodiments, an isolated anti-CD40 antibody is provided, comprising V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:2 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:10-26 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:48-51 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids; and V L The V LIt comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:63-72 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:78 or variants thereof, the variants comprising substitutions of up to about 3 amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:102-110 or variants thereof, the variants comprising substitutions of up to about 3 amino acids.

[0021] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:144-166 H Includes HC-CDR1, HC-CDR2, and HC-CDR3, as well as V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:197-213 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0022] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: (i) V H It contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:197. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (ii)V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:198. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii)V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:199. LIncludes LC-CDR1, LC-CDR2 and LC-CDR3; (iv)V H It contains V as shown in the amino acid sequence SEQ ID NO:146. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:200. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (v)V H It contains V as shown in the amino acid sequence SEQ ID NO:148. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:202. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vi)V H It contains V as shown in the amino acid sequence SEQ ID NO:150. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:202. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (vii)V H It contains V as shown in the amino acid sequence SEQ ID NO:151. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:204. L Includes LC-CDR1, LC-CDR2 and LC-CDR3; (viii)V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:205. L Includes LC-CDR1, LC-CDR2, and LC-CDR3; (ix)V H It contains V as shown in the amino acid sequence SEQ ID NO:152. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:206.L Includes LC-CDR1, LC-CDR2, and LC-CDR3; or (x)V H It contains V as shown in the amino acid sequence SEQ ID NO:160. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:200. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0023] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: (i) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102, or the V L (ii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:103, or the V L (iii) V variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:64; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102, or the V L Variants whose LC-CDRs contain substitutions of up to about 5 amino acids; (iv) V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:49, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:104, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (v)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:51, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:104, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vi)V HThe V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:66; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (vii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:106, or the V L The variants, whose LC-CDRs contain substitutions of up to about 5 amino acids; (viii)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:50, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:67; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:107, or the V LVariants whose LC-CDRs contain substitutions of up to about 5 amino acids; or (ix)V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:21; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:50, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:64; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0024] In some embodiments, any of the isolated anti-CD40 antibodies described above, the isolated anti-CD40 antibody comprises: V H It comprises any of the amino acid sequences shown in SEQ ID NOs:144-166 or variants thereof, said variants having at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:144-166; and V L It comprises any of the amino acid sequences shown in SEQ ID NOs:197-213 or variants thereof, wherein the variants have at least about 90% sequence identity with any of the amino acid sequences shown in SEQ ID NOs:197-213.

[0025] In some embodiments, an isolated anti-CD40 antibody comprises: (i) V H It comprises the amino acid sequence SEQ ID NO:144 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:144; and V L It contains the amino acid sequence SEQ ID NO:197 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:197; (ii) V H It comprises the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:145; and V LIt contains the amino acid sequence SEQ ID NO:198 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:198; (iii) V H It comprises the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:145; and V L It contains the amino acid sequence SEQ ID NO:199 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:199; (iv)V H It comprises the amino acid sequence SEQ ID NO:146 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:146; and V L It contains the amino acid sequence SEQ ID NO:200 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:200; (v)V H It comprises the amino acid sequence SEQ ID NO:148 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:148; and V L It contains the amino acid sequence SEQ ID NO:202 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:202; (vi)V H It comprises the amino acid sequence SEQ ID NO:150 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:150; and V L It contains the amino acid sequence SEQ ID NO:202 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:202; (vii)V H It comprises the amino acid sequence SEQ ID NO:151 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:151; and V L It contains the amino acid sequence SEQ ID NO:204 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:204; (viii)V H It comprises the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:145; and V LIt contains the amino acid sequence SEQ ID NO:205 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:205; (ix)V H It comprises the amino acid sequence SEQ ID NO:152 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:152; and V L It comprises the amino acid sequence SEQ ID NO:206 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:206; or (x)V H It comprises the amino acid sequence SEQ ID NO:160 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:160; and V L It contains the amino acid sequence SEQ ID NO:200 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence SEQ ID NO:200.

[0026] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H It contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:214. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0027] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:73; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0028] In some embodiments, any of the isolated anti-CD40 antibodies described above, the isolated anti-CD40 antibody comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:144 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:144; and V L It contains the amino acid sequence shown in SEQ ID NO:214 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:214.

[0029] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H It contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:215. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0030] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:74; LC-CDR2, which contains the amino acid sequence SEQ ID NO:79; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:111, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0031] In some embodiments, any of the isolated anti-CD40 antibodies described above, the isolated anti-CD40 antibody comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:144 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:144; and V LIt contains the amino acid sequence shown in SEQ ID NO:215 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:215.

[0032] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H It contains V as shown in the amino acid sequence SEQ ID NO:167. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:216. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0033] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:27; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:52, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:75; LC-CDR2, which contains the amino acid sequence SEQ ID NO:80; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:112, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0034] In some embodiments, any of the isolated anti-CD40 antibodies described above, the isolated anti-CD40 antibody comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:167 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:167; and V L It contains the amino acid sequence shown in SEQ ID NO:216 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:216.

[0035] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V HIt contains V as shown in the amino acid sequence SEQ ID NO:168. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:217. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0036] In some embodiments, an isolated anti-CD40 antibody is provided, comprising: V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:28; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:53, or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:76; LC-CDR2, which contains the amino acid sequence SEQ ID NO:81; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:113, or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0037] In some embodiments, any of the isolated anti-CD40 antibodies described above, the isolated anti-CD40 antibody comprises: V H It comprises the amino acid sequence shown in SEQ ID NO:168 or a variant thereof, said variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:168; and V L It contains the amino acid sequence shown in SEQ ID NO:217 or a variant thereof, the variant having at least about 90% sequence identity with the amino acid sequence shown in SEQ ID NO:217.

[0038] In some embodiments, the Kd value of the isolated anti-CD40 antibody binding to human CD40 is 0.1 pM to 1 nM.

[0039] In some embodiments, an isolated anti-CD40 antibody is provided that competes with any of the isolated anti-CD40 antibodies described above for specific binding to CD40. In some embodiments, an isolated anti-CD40 antibody is provided that specifically binds to the same epitope as any of the isolated anti-CD40 antibodies described above.

[0040] In some embodiments, the isolated anti-CD40 antibody, as described above, comprises an Fc fragment. In some embodiments, the isolated anti-CD40 antibody is a full-length IgG antibody. In some embodiments, the isolated anti-CD40 antibody is a full-length IgG1, IgG2, IgG3, or IgG4 antibody. In some embodiments, the isolated anti-CD40 antibody is chimeric, fully human, or humanized. In some embodiments, the isolated anti-CD40 antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain antibody (scFv), Fv fragment, dAb, Fd, nanobody, diabody, and linear antibody.

[0041] In some embodiments, an isolated nucleic acid molecule is provided, the nucleic acid molecule encoding any of the anti-CD40 antibodies described above. In some embodiments, a vector is provided, the vector comprising any of the nucleic acid molecules described above. In some embodiments, a host cell is provided, the host cell comprising any of the anti-CD40 antibodies described above, any of the nucleic acid molecules described above, or any of the vectors described above. In some embodiments, a method for preparing an anti-CD40 antibody is provided, comprising: a) culturing any of the above-described host cells under conditions that enable efficient expression of the anti-CD40 antibody; and b) obtaining the expressed anti-CD40 antibody from the host cell.

[0042] In some embodiments, a method of treating a desired individual disease or condition is provided, comprising administering an effective amount of any of the anti-CD40 antibodies described above to the individual. In some embodiments, the use of any of the anti-CD40 antibodies described above in the preparation of a pharmaceutical composition for treating a desired individual disease or condition is provided. In some embodiments, the use of any of the anti-CD40 antibodies described above or a pharmaceutical composition comprising an anti-CD40 antibody in the preparation of a medicament for treating a disease or condition is provided. In some embodiments, the disease or condition is related to the CD40 signaling pathway, including autoimmune diseases and / or inflammatory conditions and / or cancer and / or transplant-related diseases or conditions. In some embodiments, the disease or condition is selected from, for example, systemic lupus erythematosus (SLE), discoid lupus erythematosus, lupus nephritis, inflammatory arthritis: including but not limited to juvenile arthritis, rheumatoid arthritis, psoriatic arthritis, Reiter's syndrome, ankylosing spondylitis and gouty arthritis, organ or tissue transplant rejection: hyperacute, acute or chronic rejection and / or graft-versus-host disease, multiple sclerosis, hyperIgE syndrome, polyinflammatory nodules, primary biliary cirrhosis, inflammatory bowel disease, Crohn's disease, celiac disease (gluten-sensitive bowel disease), autoimmune hepatitis, pernicious anemia, autoimmune hemolytic anemia, scleroderma, myasthenia gravis, idiopathic thrombocytopenic purpura, autoimmune thyroiditis, Grave's disease, Hashimoto's thyroiditis. Thyroiditis, immune complex diseases, chronic fatigue immune dysfunction syndrome (CFIDS), polymyositis, dermatomyositis, cryoglobulinemia, thrombolysis, cardiomyopathy, pemphigus vulgaris, pulmonary interstitial fibrosis, type I and type II diabetes, delayed-type hypersensitivity reactions of types 1, 2, 3 and 4, allergic or anaphylactic diseases, unwanted / accidental immune responses to therapeutic proteins (e.g., factor VII in hemophilia), asthma, Rich-Strauss syndrome (allergic granulomatous disease), atopic dermatitis, allergic and irritant contact dermatitis, urticaria, IgE-mediated allergy, atherosclerosis, vasculitis, idiopathic inflammatory myopathy, hemolytic diseases, Alzheimer's disease, chronic inflammatory demyelinating polyneuropathy, Sjögren's syndrome Diseases including psoriasis, hidradenitis suppurativa, purulent urethritis, sarcoidosis, ulcerative colitis, and tumors including but not limited to non-Hodgkin's lymphoma, chronic lymphocytic leukemia, multiple myeloma, B-cell lymphoma, high / intermediate / low-grade B-cell lymphoma, acute B-cell lymphoblastic leukemia, granulocytic leukemia, and Hodgkin's disease; nephritis, acute respiratory distress syndrome, epididymitis, glomerulonephritis, and hyperthyroidism.

[0043] It also provides pharmaceutical compositions, kits, and manufactured products containing any of the anti-CD40 antibodies described above. Attached Figure Description

[0044] Figure 1A-1C The results shown demonstrate the binding affinity of the exemplary anti-CD40 antibody to CD40 from different species compared to the control antibody ASKP1240. Figure 1A The results shown are the binding curves of anti-CD40 antibodies K1 and K2 with human CD40. Figure 1B The results shown are the binding curves of anti-CD40 antibodies K1 and K2 with rhesus monkey CD40. Figure 1C The results shown are the binding curves of anti-CD40 antibodies K1 and K2 with rabbit CD40.

[0045] Figure 2A The results show that, compared with the control antibody ASKP1240, anti-CD40 antibodies K1 and K2 inhibited human CD40L-induced CD95 expression in Ramos cells. Figure 2B The results show that after cross-linking with anti-immunoglobulin antibodies, anti-CD40 antibodies K1 and K2 and control antibody ASKP1240 have almost no side effects of activating the CD40 pathway, but control antibody CFZ533 shows some agonistic activity.

[0046] Figure 3 The results show that, compared with the control antibody ASKP1240, anti-CD40 antibodies K1 and K2 inhibited CD40L-induced CD23 expression in PBMCs.

[0047] Figures 4A-4B The results show that, compared with the control antibody ASKP1240, anti-CD40 antibodies K1 and K2 inhibited the secretion of CD40L-induced cytokines in iDCs. Figure 4A The results show that anti-CD40 antibodies K1 and K2 inhibit CD40L-induced IL12p40 secretion in iDCs. Figure 4B The results show that anti-CD40 antibodies K1 and K2 inhibit CD40L-induced TNF-α secretion in iDCs.

[0048] Figure 5 The results show that, compared with the control antibody ASKP1240, the humanized anti-CD40 antibodies K11 and K51 inhibited the activation of the human CD40L-induced NF-κB signaling pathway.

[0049] Figures 6A-6C The results shown demonstrate the binding affinity of the humanized anti-CD40 antibody to CD40 from different species compared to the control antibody ASKP1240. Figure 6AThe diagram shows the binding curves of humanized anti-CD40 antibodies K11 and K51 to human CD40. Figure 6B The diagram shows the binding curves of humanized anti-CD40 antibodies K11 and K51 to rhesus monkey CD40. Figure 6C The diagram shows the binding curves of humanized anti-CD40 antibodies K11 and K51 to rabbit CD40.

[0050] Figure 7A The results show that, compared with the control antibody ASKP1240, the humanized anti-CD40 antibodies K11 and K51 inhibited human CD40L-induced CD95 expression in Ramos cells. Figure 7B The results show that after cross-linking with anti-immunoglobulin antibodies, the humanized anti-CD40 antibody K11 has almost no side effect of activating the CD40 pathway.

[0051] Figure 8 The results show that, compared with the control antibody ASKP1240, the humanized anti-CD40 antibodies K11 and K51 inhibited CD40L-induced CD23 expression in PBMCs.

[0052] Figures 9A-9B The results show that, compared with the control antibody ASKP1240, the humanized anti-CD40 antibodies K11 and K51 inhibited CD40L-induced cytokine secretion in iDCs. Figure 9A The results shown indicate that humanized anti-CD40 antibodies K11 and K51 inhibit CD40L-induced IL12p40 secretion in iDCs. Figure 9B The results shown indicate that humanized anti-CD40 antibodies K11 and K51 inhibit CD40L-induced TNF-α secretion in iDCs.

[0053] Figure 10 shows the blocking effect of the humanized anti-CD40 antibody on T cell-dependent antibody responses compared with the control antibody ASKP1240. Figure 10A The results show that the humanized anti-CD40 antibody K11 almost completely blocked the production of IgG specific to the KLH antigen. Figure 10B The results shown indicate that the humanized anti-CD40 antibody K11 almost completely blocked the production of IgM specific to the KLH antigen.

[0054] Figure 11A-11C The results shown demonstrate the binding affinity of the optimized anti-CD40 antibody to CD40 from different species compared to the control antibody ASKP1240. Figure 11A The figure shows the binding curves of the optimized anti-CD40 antibodies K21, K24, and K30 with human CD40. Figure 11B The figure shows the binding curves of the optimized anti-CD40 antibodies K21, K24, and K30 with rhesus monkey CD40. Figure 11C The figure shows the binding curves of the optimized anti-CD40 antibodies K21, K24, and K30 with rabbit CD40.

[0055] Figures 12A-12C The results shown indicate the cross-reactivity of the optimized anti-CD40 antibody with TNFRSF11A or TNFR2 compared to the control antibody ASKP1240. Figure 12A The results show that the optimized antibody K21 does not cross-react with TNFRSF11A or TNFR2. Figure 12B The results show that the optimized antibody K24 does not cross-react with TNFRSF11A or TNFR2. Figure 12C The results show that the optimized antibody K30 does not cross-react with TNFRSF11A or TNFR2.

[0056] Figure 13A The results show that, compared with the control antibody ASKP1240, the optimized anti-CD40 antibodies K21, K24, and K30 inhibited human CD40L-induced CD95 expression in Ramos cells. Figure 13B The results show that after cross-linking with anti-immunoglobulin antibodies, the optimized anti-CD40 antibodies K21, K24, and K30 have almost no side effects of activating the CD40 pathway.

[0057] Figure 14 The results show that, compared with the control antibody ASKP1240, the optimized anti-CD40 antibodies K21, K24, and K30 inhibited CD40L-induced CD23 expression in PBMCs.

[0058] Figures 15A-15C The results shown are the pharmacokinetic analysis of the optimized anti-CD40 antibodies K21, K24, and K30 in human CD40 transgenic mice compared with the control antibody ASKP1240. Figure 15A The results shown are the optimized serum concentration curves of anti-CD40 antibodies K21, K24, and K30. Figure 15B The results shown are the elimination phase half-lives of the optimized anti-CD40 antibodies K21, K24, and K30. Figure 15C The results shown are the AUClast values ​​of the optimized anti-CD40 antibodies K21, K24, and K30.

[0059] Figure 16 shows the blocking effect of different doses of anti-CD40 antibody on T cell-dependent antibody response compared with the control antibody ASKP1240. Figure 16AThe results show that the optimized anti-CD40 antibody K21 almost completely blocked the production of KLH antigen-specific IgG at a dose of 3 mpk, and partially blocked the production of anti-KLH IgG at a dose of 1 mpk. Figure 16B The results show that the optimized anti-CD40 antibody K21 almost completely blocked the production of IgM specific to the KLH antigen at a dose of 3 mpk, and partially blocked the production of anti-KLH IgM at a dose of 1 mpk. Figure 16C The results show that the optimized anti-CD40 antibody K24 almost completely blocked the production of KLH antigen-specific IgG at a dose of 3 mpk, and effectively blocked the production of anti-KLH IgG at a dose of 1 mpk. Figure 16D The results show that the optimized anti-CD40 antibody K24 almost completely blocked the production of IgM specific to the KLH antigen at a dose of 3 mpk, and effectively blocked the production of anti-KLH IgM at a dose of 1 mpk. Figure 16E The results show that the optimized anti-CD40 antibody K30 almost completely blocked the production of KLH antigen-specific IgG at a dose of 3 mpk, and partially blocked the production of anti-KLH IgG at a dose of 1 mpk. Figure 16F The results show that the optimized anti-CD40 antibody K30 almost completely blocked the production of IgM specific to the KLH antigen at a dose of 3 mpk, and partially blocked the production of anti-KLH IgM at a dose of 1 mpk.

[0060] Detailed description of this application

[0061] This application provides an anti-CD40 antibody molecule. Through a combination of hybridoma technology, scFv phage library screening, humanization technology, affinity maturation, and appropriately designed biochemical and biological experiments, a highly efficient antibody molecule capable of binding to human CD40 and inhibiting the interaction between human CD40 and its receptor has been identified. The results presented herein demonstrate that, compared to the known anti-CD40 antibody ASKP1240, the antibody in this application binds to human, rabbit, and / or monkey CD40 with high affinity, and surprisingly, various biological experiments have shown that the antibody in this application is even more effective than ASKP1240.

[0062] The anti-CD40 antibodies provided in this application include, for example, full-length anti-CD40 antibodies, anti-CD40 single-chain antibodies (scFvs), anti-CD40 Fc fusion proteins, multispecific (e.g., bispecific) anti-CD40 antibodies, anti-CD40 immunoconjugates, and the like.

[0063] On the other hand, this application provides an anti-CD40 antibody, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (VH ), the V H Includes: a heavy chain complementarity determination region (HC-CDR)1 containing GYYWS (SEQ ID NO:1); HC-CDR2 containing X1IGGSSX2X3TX4YNPSLKS (SEQ ID NO:114), where X1 is A or F, X2 is G or S, X3 is S or T, and X4 is G or N; and HC-CDR3 containing QPX1X2X3RSX4FX5Y (SEQ ID NO:116), where X1 is A, N, or Q, X2 is A, F, Q, V, W, or Y, X3 is A or Y, X4 is A, G, P, Q, or S, and X5 is A, F, H, K, Q, V, or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes KSSQSLLYX1X2NX3KNYLA (SEQ ID NO:118), wherein X1 is R, S or O, X2 is G, L, M, S, V or Y, and X3 is G, N or O; LC-CDR2, which includes WASTRES (SEQ ID NO:77); and LC-CDR3, which includes X1QYX2X3X4PT (SEQ ID NO:120), wherein X1 is A, G, M, Q or S, X2 is L, W or Y, X3 is A, G, H, S or V, and X4 is A, F, H, K, L, R, S, T, W or Y.

[0064] On the other hand, this application provides an anti-CD40 antibody, wherein the anti-CD40 antibody comprises a heavy chain variable domain (V H ), the V H Includes: a heavy chain complementarity determination region (HC-CDR)1 containing RYAMH (SEQ ID NO:2); HC-CDR2 containing X1IWFDGX2X3X4YYADSVKD (SEQ ID NO:115), wherein X1 is A or G, X2 is G, N or R, X3 is A, G, K, M, Q or S, and X4 is A, D, E, K, M, N, Q, R, S or V; and HC-CDR3 containing DYDX1GX2SX3YFDY (SEQ ID NO:117), wherein X1 is A or S, X2 is W or Y, and X3 is F or Y; and a light chain variable structural domain (V L ), the V LIt includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQX1IX2X3X4LX5 (SEQ ID NO:119), wherein X1 is G, I, R or Y, X2 is S or T, X3 is G, L, M or S, X4 is W or Y, and X5 is A or S; LC-CDR2, which includes YASNLES (SEQ ID NO:78); and LC-CDR3, which includes QQX1KX2YPLT (SEQ ID NO:121), wherein X1 is A, H, S or V, and X2 is K, L, M, R, S or T.

[0065] On the other hand, this application provides an anti-CD40 antibody, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains RYAMH (SEQ ID NO:2); HC-CDR2, which contains GIWFDGNKRYYADSVKD (SEQ ID NO:10); and HC-CDR3, which contains DYDSGYSYYFDY (SEQ ID NO:48); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQGTNNYLA (SEQ ID NO:73); LC-CDR2, which includes YASNLES (SEQ ID NO:78); and LC-CDR3, which includes QQHKSYPLT (SEQ ID NO:102).

[0066] On the other hand, this application provides an anti-CD40 antibody, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H Includes: heavy chain complementarity-determining region (HC-CDR)1, which contains RYAMH (SEQ ID NO:2); HC-CDR2, which contains GIWFDGNKRYYADSVKD (SEQ ID NO:10); and HC-CDR3, which contains DYDSGYSYYFDY (SEQ ID NO:48); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQSISRWLA (SEQ ID NO:74); LC-CDR2, which includes KASSLES (SEQ ID NO:79); and LC-CDR3, which includes LQHNSYPLT (SEQ ID NO:111).

[0067] On the other hand, this application provides an anti-CD40 antibody, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity determination region (HC-CDR)1, which contains SGYYWS (SEQ ID NO:3); HC-CDR2, which contains YISYSGSTSYNPSLKS (SEQ ID NO:27); and HC-CDR3, which contains EVTGVTYGD (SEQ ID NO:52); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQGISSYLN (SEQ ID NO: 75); LC-CDR2, which includes YANRLES (SEQ ID NO: 80); and LC-CDR3, which includes QQYNSLPWT (SEQ ID NO: 112).

[0068] On the other hand, this application provides an anti-CD40 antibody, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H It includes: heavy chain complementarity-determining region (HC-CDR)1, which contains SNYWS (SEQ ID NO:4); HC-CDR2, which contains RIFASGGTTDYNPSLKS (SEQ ID NO:28); and HC-CDR3, which contains EPMYSSGWFYS (SEQ ID NO:53); and light chain variable structural domain (V L ), the V L It includes: light chain complementarity determination region (LC-CDR)1, which includes RASQSVGSYLA (SEQ ID NO:76); LC-CDR2, which includes GASSRAT (SEQ ID NO:81); and LC-CDR3, which includes QQGSNALT (SEQ ID NO:113).

[0069] It also provides nucleic acids encoding anti-CD40 antibodies, compositions containing anti-CD40 antibodies, and methods for preparing and using anti-CD40 antibodies.

[0070] definition

[0071] As described herein, “treatment” or “treating” is a method of obtaining a beneficial or desired outcome, including clinical outcomes. For the purposes of this application, the beneficial or desired clinical outcome includes, but is not limited to, one or more of the following: relief of one or more symptoms caused by a disease, reduction of disease severity, stabilization of the disease (e.g., prevention or delay of disease exacerbation), prevention or delay of disease spread (e.g., metastasis), prevention or delay of disease recurrence, delay or slowing of disease progression, improvement of disease status, relief of the disease (partial or complete), reduction of the dosage of one or more other medications required to treat the disease, delay of disease progression, improvement or enhancement of quality of life, weight gain, and / or prolonged survival. Simultaneously, “treatment” also includes a reduction in disease pathological outcomes (e.g., tumor volume in the case of cancer). The methods of this application consider any one or more aspects of these treatments.

[0072] The term "antibody" includes both full-length antibodies and their antigen-binding fragments. Full-length antibodies consist of two heavy chains and two light chains. Variable regions in both the light and heavy chains are responsible for antigen binding. The variable regions in both chains typically include three hypervariable loops, known as complementarity-determining regions (CDRs) (light chain (LC) CDRs include LC-CDR1, LC-CDR2, and LC-CDR3; heavy chain (HC) CDRs include HC-CDR1, HC-CDR2, and HC-CDR3). The CDR boundaries of the antibodies or antigen-binding fragments disclosed herein can be defined or identified according to the Kabat, Chothia, or Al-Lazikani conventions (Al-Lazikani 1997; Chothia 1985; Chothia 1987; Chothia 1989; Kabat 1987; Kabat 1991). Three CDR regions of the heavy or light chain are inserted between flanking segments called framework regions (FRs), which are more conserved than the CDR regions and form a scaffold supporting the hypervariable loop. The constant regions of the heavy and light chains do not participate in antigen binding but exhibit a variety of effector functions. Antibodies are classified based on the amino acid sequence of their heavy chain constant regions. The five main classes or isotypes of antibodies are IgA, IgD, IgE, IgG, and IgM, characterized by having α, δ, ε, γ, and μ-type heavy chains, respectively. Several major antibody classes are subclassed, such as IgG1 (γ1 heavy chain), IgG2 (γ2 heavy chain), IgG3 (γ3 heavy chain), IgG4 (γ4 heavy chain), IgA1 (α1 heavy chain), or IgA2 (α2 heavy chain).

[0073] As described herein, the term "antigen-binding fragment" refers to an antibody fragment, including, for example, a diabody, Fab, Fab', F(ab')2, Fv fragment, disulfide-stabilized Fv fragment (dsFv), (dsFv)2, bispecific dsFv (dsFv-dsFv'), disulfide-stabilized diabody (ds-ds-ds-fv), single-chain antibody (scFv), scFv dimer (bivalent diabody), multispecific antibody, single-domain antibody, nanobody, domain antibody, divalent domain antibody, or any other antibody fragment capable of binding to an antigen but not containing a complete antibody structure. The antigen-binding fragment is capable of binding the same antigen to a parent antibody or a parent antibody fragment (such as a parental scFv). In some embodiments, the antigen-binding fragment may include one or more CDRs from a specific human antibody that have been grafted into a frame region from one or more different human antibodies.

[0074] As described herein, the term "epitope" refers to a specific set of atoms or amino acids on an antigen that an antibody or antibody portion binds to. If two antibodies or antibody portions exhibit competitive binding to an antigen, they may bind to the same epitope on the antigen.

[0075] As used herein, when the first antibody inhibits the binding of the second antibody to the CD40 target by at least 50% (e.g., at least 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%) at an equimolar concentration, the first antibody “competitively” binds to the CD40 target with the second antibody, and vice versa. PCT Publication WO 03 / 48731 describes a high-throughput antibody “epitope classification” method based on cross-competition.

[0076] As described herein, the terms "specifically bind," "specifically recognize," or "specific to" refer to measurable and reproducible interactions, such as antibody binding to a target that confirms the presence of that target in a heterogeneous group of molecules, including biomolecules. For example, an antibody's ability to specifically recognize a target (which may be an epitope) means that the antibody binds to that target with higher affinity, stronger binding, and / or more persistent binding compared to binding to other targets. In some embodiments, an antibody that specifically recognizes an antigen reacts with one or more antigenic determinants of the antigen with a binding affinity at least 10 times greater than its binding affinity to other targets.

[0077] As described herein, an “isolated” anti-CD40 antibody is an anti-CD40 antibody that (1) is not related to a naturally occurring protein, (2) does not contain other proteins of the same origin, (3) is expressed by cells of a different species, or (4) does not exist in nature.

[0078] As described herein, the term “isolated nucleic acid” refers to a nucleic acid or combination thereof of genomic, cDNA, or synthetic origin. Depending on its origin, “isolated nucleic acid” means that it is (1) unrelated to all or part of the polynucleotides in “isolated nucleic acids” found in nature, (2) operablely ligable to polynucleotides not naturally associated with it, or (3) not present in nature as part of a longer sequence.

[0079] As used herein, the term “CDR” or “complementarity-determining region” refers to a discontinuous antigen-binding site found within the variable domains of heavy and light chain polypeptides. In the literature Kabat et al., J. Biol. Chem. 252: 6609-6616 (1977); Kabat et al., USDept. of Health and Human Services, "Sequences of proteins of immunological interest" (1991); Chothia et al., J. Mol. Biol. 196: 901-917 (1987); Al-Lazikani B. et al. al., J. Mol. Biol., 273: 927-948 (1997); MacCallum et al., J. Mol. Biol. 262: 732-745 (1996); Abhinandan and Martin, Mol. Immunol., 45: 3832-3839 (2008); Lefranc MPet These specific regions have been described in al., Dev. Comp. Immunol., 27:55-77 (2003); and Honegger and Plückthun, J. Mol. Biol., 309:657-670 (2001), where these definitions include overlaps or subsets of amino acid residues when compared with each other. However, any definition used to indicate a CDR of an antibody or transplanted antibody or its variants is included within the scope of the terminology defined and used herein. Table 1 lists the positions of the amino acid residues included in the CDRs defined by the aforementioned references for comparison. Algorithms and interfaces for CDR prediction are known in the art, including, for example, those described in Abhinandan and Martin, Mol. Immunol., 45:3832-3839 (2008); Ehrenmann F. et al., Nucleic Acids Res., 38:D301-D307 (2010); and Adolf-Bryfogle J. et al., Nucleic Acids Res., 43:D432-D438 (2015). The entire contents of the references cited in this paragraph are incorporated herein by reference for the purposes of this application and one or more claims that may be included herein.

[0080] Table 1: CDR Definition

[0081]

[0082]

[0083] 1 The amino acid residue numbering follows the nomenclature method described in Kabat et al. above.

[0084] 2 The amino acid residue numbering follows the nomenclature method described in Chothia et al. above.

[0085] 3 The amino acid residue numbering follows the nomenclature method described in MacCallum et al. above.

[0086] 4 The amino acid residue numbering follows the nomenclature method described in Lefranc et al. above.

[0087] 5 The amino acid residue numbering follows the nomenclature method described in Honegger and Plückthun.

[0088] The term "chimeric antibody" refers to an antibody in which a portion of the heavy chain and / or light chain is identical or homologous to the corresponding sequence in an antibody from a particular species or belonging to a particular antibody species or subclass, while the remainder of the chain is identical or homologous to the corresponding sequence in an antibody from another genus or belonging to another antibody species or subclass, as well as fragments of such antibodies, provided they possess the biological activity described in this application (see US Patent No. 4,816,567; and Morrison et al., Proc. Natl. Acad. Sci. USA, 81:6851-6855 (1984)).

[0089] "Fv" is the smallest antibody fragment containing a complete antigen recognition and binding site. This fragment is a dimer formed by a heavy chain variable domain and a light chain variable domain tightly and non-covalently linked. The folding of these two domains derives six hypervariable rings (three in the light chain and three in the heavy chain), which provide the antibody with amino acid residues for binding to the antigen and confer the antibody's specificity for antigen binding. However, even a single variable domain (or half of the Fv fragment, containing only three antigen-specific CDRs) can recognize and bind to antigens, although its affinity is lower than that of the complete binding site.

[0090] "Single-chain Fv", also abbreviated as "sFv" or "scFv", is a type of Fv containing V molecules linked together to form a single polypeptide chain. H and V L Antibody fragments of antibody domains. In some embodiments, the scFv polypeptide further includes V H and V LThe linker polypeptide between the domains allows scFv to form an ideal structure for antigen binding. For an overview of scFv, see Pluckthun in The Pharmacology of Monoclonal Antibodies, vol. 113, Rosenburg and Moore eds., Springer-Verlag, New York, pp. 269-315 (1994).

[0091] The term "diabodies" is used in V H and V L Small antibody fragments are prepared by constructing scFv fragments (see above) using short linkers (e.g., 5–10 residues) between domains. This allows the variable domains to pair between chains rather than within chains, resulting in a bivalent fragment, i.e., a fragment with two antigen-binding sites. Bispecific double-chain antibodies are heterodimers of two “crossed” scFv fragments, where the V0 of the two antibodies... H and V L The domains are located on different polypeptide chains. Double-chain antibodies are fully described in EP 404,097; WO 93 / 11161; Hollinger et al., Proc. Natl. Acad. Sci. USA, 90:6444-6448 (1993).

[0092] The “humanized” form of non-human (e.g., rodent) antibodies is a chimeric antibody, which includes a minimal sequence derived from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (receptor antibodies), where the hypervariable region (HVR) residues of the receptor antibody are replaced by hypervariable region residues from non-human species such as mice, rats, rabbits, or non-human mammals that possess desirable antibody specificity, affinity, and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced by corresponding non-human residues. Additionally, humanized antibodies may include residues not present in either the receptor or donor antibody. These modifications can further improve antibody performance. Typically, humanized antibodies contain substantially all, at least one, and usually two variable domains, where all or substantially all of the hypervariable loops correspond to the hypervariable loops of a non-human immunoglobulin, and all or substantially all of the framework regions are human immunoglobulin sequences. Humanized antibodies may also optionally include at least a portion of the immunoglobulin constant region (Fc), typically the constant region of a human immunoglobulin. For details, please refer to Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992).

[0093] The "percentage of amino acid sequence identity (%)" or "homology" of the peptide and antibody sequences identified in this paper is defined as the percentage of identical amino acid residues in a candidate sequence compared to a peptide sequence, assuming that conserved substitutions are part of sequence identity. The percentage of amino acid sequence identity can be determined using various alignment methods within the scope of the art, such as publicly available computer software like BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Those skilled in the art can determine suitable parameters for measuring alignment, including any algorithm required to maximize alignment across the full length of the compared sequences. However, for the purposes of this paper, the percentage of amino acid sequence identity values ​​were generated using the sequence alignment computer program MUSCLE (Edgar, RC, Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, RC, BMC Bioinformatics 5(1):113, 2004).

[0094] The term "Fc receptor" or "FcR" is used to describe receptors that bind to the Fc region of antibodies. In some embodiments, the FcR described in this application is an FcR that binds to IgG antibodies (a type of γ receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and alternative splicing forms of these receptors. FcγRII receptors include FcγRIIA ("activating receptor") and FcγRIIB ("inhibiting receptor"), which have similar amino acid sequences and differ primarily in their cytoplasmic domains. The cytoplasmic domain of the activating receptor FcγRIIA contains an immunoreceptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains an immunoreceptor tyrosine inhibitory motif (ITIM) (see M.in.). Annu.Rev.Immunol.15:203-234 (1997)). The term also includes allotypes, such as FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131 and / or FcγRIIA-H131. FcRs are described in Ravetch and Kinet, Annu.Rev.Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J.Lab.Clin.Med.126:330-41 (1995). In this application, the term FcR covers other types of FcRs, including those to be identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for transferring maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994)).

[0095] The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC), consisting of an α-chain non-covalently bound to β2-microglobulin. The various functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from the mother to the newborn and in regulating serum IgG levels. As a rescue receptor, FcRn can bind and transport endocytotic IgG in its intact form both intracellularly and intercellularly, protecting it from the default degradation pathway.

[0096] The "CH1 domain" of the human IgG Fc region typically extends from amino acid 118 to amino acid 215 (EU numbering system).

[0097] The "hinge region" is typically defined as extending from Glu at position 216 to Pro at position 230 of human IgG1 (Burton, Molec. Immunol. 22:161-206 (1985)). By placing the first and last cysteine ​​residues that form the inter-heavy chain disulfide bond at the same positions as IgG1, it is possible to align the hinge regions of other IgG isotypes with the IgG1 sequence.

[0098] The "CH2 domain" of the human IgG Fc region typically extends from amino acid 231 to amino acid 340. The unique feature of the CH2 domain is that it does not pair tightly with another region; instead, two N-terminal branched sugar chains are inserted between the two CH2 domains of the intact native IgG molecule. It is speculated that the sugars may act as a substitute for domain-to-domain pairing, helping to maintain the stability of the CH2 domain. (Burton, Molec. Immunol. 22:161-206 (1985)).

[0099] The “CH3” domain includes the extension from the C-terminal residue to the CH2 domain within the Fc region (from amino acid 341 to the C-terminus of the antibody sequence, typically amino acid 446 or 447 of IgG).

[0100] "Functional Fc fragments" possess the "effective functions" inherent in the natural Fc region sequence. Exemplary "effective functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; and downregulation of cell surface receptors (such as B cell receptors; BCR). These effector functions typically require the Fc region to bind to a binding domain (such as the antibody variable region) and can be evaluated using a variety of experimental methods known in the art.

[0101] Antibodies with IgG Fc variants exhibiting "altered" FcR binding affinity or ADCC activity show enhanced or weakened FcR binding and / or ADCC activity compared to the parent peptide or peptides containing the native Fc sequence. Fc variants exhibiting "enhanced binding" to FcRs have higher binding affinity (e.g., lower apparent Kd or IC50) to at least one FcR compared to the parent peptide or peptides containing the native IgG Fc sequence. 50(Value). In some embodiments, the binding affinity is enhanced by 3 times compared to the parent peptide, for example, 5, 10, 25, 50, 60, 100, 150, 200, or even up to 500 times, or the binding affinity is increased by 25% to 1000%. Fc variants exhibit “reduced binding” to FcRs, having a lower affinity for at least one FcR compared to the parent peptide (e.g., higher apparent Kd or IC). 50 (Value). Compared with the parent peptide, its binding ability is reduced by 40% or more.

[0102] Antibody-dependent cell-mediated cytotoxicity (ADCC) is a form of cytotoxicity in which secreted Ig binds to Fc receptors (FcRs) present on certain cytotoxic cells (e.g., natural killer (NK) cells, neutrophils, and macrophages). This allows these cytotoxic effector cells to specifically bind to target cells carrying antigens and subsequently kill the target cells using cytotoxins. Antibodies "arm" the cytotoxic cells and are essential for this killing. Among the main cell types mediating ADCC, NK cells express only FcγRIII, while monocytes express FcγRI, FcγRII, and FcγRIII. The expression of FcRs on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991). The ADCC activity of target molecules can be assessed by in vitro ADCC experiments, described in U.S. Patent Nos. 5,500,362 or 5,821,337. Effector cells suitable for such experiments include peripheral blood mononuclear cells (PBMCs) and natural killer cells (NK cells). Alternatively, or additionally, the ADCC activity of the target molecule can also be assessed in vivo, as described, for example, in animal models disclosed in Clynes et al. PNAS (USA) 95:652-656 (1998).

[0103] Peptides containing Fc region variants exhibit "enhanced ADCC activity" or are more effective at mediating ADCC effects in the presence of human effector cells compared to peptides containing wild-type IgG Fc or parental peptides. These peptides, when experimentally present in substantially the same quantity as those containing wild-type IgG Fc (or parental peptides), mediate ADCC more effectively both in vitro and in vivo. Such variants are typically identified using any in vitro ADCC assay known in the art, such as experiments or methods for identifying ADCC activity, for example in animal models. In some embodiments, such variants mediate ADCC with a 5 to 100-fold, for example, 25 to 50-fold, efficiency improvement compared to wild-type Fc (or parental peptide).

[0104] "Complement-dependent cytotoxicity" or "CDC" refers to the lysis of target cells in the presence of complement. Activation of the classical complement pathway is initiated by the binding of the first component of the complement system (C1q) to an antibody (a subclass with a suitable structure) that binds to a homologous antigen. To assess complement activation, CDC assays can be performed, as described in Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996). Peptide variants with altered Fc region amino acid sequences and increased or decreased C1q binding capacity are described in U.S. Patent Nos. 6,194,551B1 and WO99 / 51642. The contents of these patent publications are expressly incorporated herein by reference. See also Idusogie et al. J. Immunol. 164:4178-4184 (2000).

[0105] Unless otherwise stated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate forms of each other and encode the same amino acid sequence. Nucleotide sequences encoding proteins or RNA may also include introns; for example, nucleotide sequences encoding proteins may contain introns in certain forms.

[0106] The term "operationally ligated" refers to a functional link between a regulatory sequence and a heterologous nucleotide sequence, thereby enabling the latter to be expressed. For example, the first and second nucleotide sequences are operably ligated when they are in a functional relationship. Similarly, if a promoter affects the transcription or expression of a coding sequence, the promoter and coding sequence are operably ligated. Typically, operably ligated DNA sequences are contiguous, and, if necessary, two protein-coding regions can be ligated within the same reading frame.

[0107] "Homology" refers to the sequence similarity or identity between two polypeptides or two nucleic acid molecules. If the same position in two compared sequences is the same base or amino acid monomer subunit, for example, if both DNA molecules have adenine at the same position, then the two DNA molecules are homologous at that position. The percentage of homology between two sequences is a function calculated by multiplying the number of matching or homologous positions in the two sequences to the total number of positions, and then multiplying by 100. For example, if 6 out of 10 positions in two sequences are matching or homologous, then the two sequences are 60% homologous. For instance, the DNA sequences ATTGCC and TATGGC have 50% homology. Generally, when comparing two sequences, the goal is to obtain the maximum homology.

[0108] The “effective amount” of the anti-CD40 antibody or composition disclosed herein refers to an amount sufficient to achieve a specific purpose. The “effective amount” can be determined empirically and by known methods associated with the stated purpose.

[0109] The term "therapeutic effective amount" refers to the amount of the anti-CD40 antibody or its composition disclosed herein that is effective in treating an individual's disease or symptoms. This includes an amount sufficient to reduce or improve the severity and / or duration of the disease or one or more of its symptoms; prevent disease progression; induce symptom resolution; prevent recurrence, development, onset, or progression of one or more disease-related symptoms; detect the disease; or enhance / improve the preventive or therapeutic effect of another therapy (e.g., a prophylactic or therapeutic agent).

[0110] As used herein, "pharmaceuticalally acceptable" or "pharmacologically compatible" means a material that has no biological activity or other undesirable properties, such as the ability to be incorporated into a pharmaceutical composition given to a patient without causing significant adverse biological reactions, or that does not interact harmfully with any other components contained in the composition. Pharmaceutically acceptable carriers or excipients preferably meet the required standards for toxicological or manufacturing testing and / or are included in the inactive ingredient guidelines prepared by the U.S. Food and Drug Administration.

[0111] The embodiments of this application described herein should be understood to include embodiments that are “composed of” and / or “substantially composed of”.

[0112] In this article, “about” is used to refer to a numerical value or parameter, including (and descriptions) variations for that value or parameter itself. For example, a description involving “about X” includes a description of “X”.

[0113] As used in this article, mentioning "not" a value or parameter usually means and describes something other than a certain value or parameter. For example, "This method cannot be used to treat type X cancer" means that this method is generally used to treat other types of cancer besides type X cancer.

[0114] Unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” used herein and in the claims include plural objects.

[0115] Anti-CD40 antibody

[0116] On one hand, this application provides anti-CD40 antibodies that specifically bind to CD40. These anti-CD40 antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules comprising heavy chain and / or light chain CDRs as described herein. On the other hand, this application provides isolated antibodies that bind to CD40. Anticipated anti-CD40 antibodies include, for example, full-length anti-CD40 antibodies (such as full-length IgG1 or IgG4), anti-CD40 single-chain antibodies, anti-CD40 Fc fusion proteins, multispecific (such as bispecific) anti-CD40 antibodies, anti-CD40 immunoconjugates, and the like. In some embodiments, the anti-CD40 antibody is a full-length antibody (such as full-length IgG1 or IgG4) or its antigen-binding fragment that specifically binds to CD40. In some embodiments, the anti-CD40 antibody is Fab, Fab', F(ab)'2, Fab'-SH, single-chain antibody (scFv), Fv fragment, dAb, Fd, nanobody, diabody, or linear antibody. In some embodiments, an antibody that specifically binds to CD40 means that the antibody's affinity for binding to CD40 is at least 10 times greater than its affinity for binding to non-target antibodies (including, for example, 10, 10). 2 10 3 10 4 10 5 10 6 , or 10 7 (Multiple times). In some embodiments, non-target refers to an antigen that is not CD40. Binding affinity can be determined by methods known in the art, such as ELISA, fluorescence activated cell sorting (FACS) analysis, or radioimmunoprecipitation analysis (RIA). Kd value can be determined by methods known in the art, such as surface plasmon resonance (SPR) technology or biolayer interference (BLI) technology.

[0117] While this document discusses anti-CD40 antibodies containing human sequences (e.g., human heavy and light chain variable domains containing human CDR sequences), non-human anti-CD40 antibodies are also considered. In some embodiments, a non-human anti-CD40 antibody comprises the human CDR sequence and non-human frame region sequence of the anti-CD40 antibody described herein. In some embodiments, the non-human frame region sequence comprises any sequence used to generate heavy and / or light chain variable domains using one or more human CDR sequences as described herein, including, for example, mammals such as mice, rats, rabbits, pigs, cattle (e.g., cows, bulls, buffalo), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., apes, macaques), etc. In some embodiments, a non-human anti-CD40 antibody comprises an anti-CD40 antibody generated by transplanting one or more human CDR sequences as described herein into a non-human frame region (e.g., a mouse or chicken frame region sequence).

[0118] The complete amino acid sequence of an exemplary human CD40 contains or consists of the amino acid sequence shown in SEQ ID NO: 222.

[0119] In some embodiments, the anti-CD40 antibody described herein specifically recognizes an epitope in human CD40. In some embodiments, the anti-CD40 antibody cross-reacts with CD40 from species other than humans. In some embodiments, the anti-CD40 antibody is completely specific to human CD40 and does not cross-react with other non-human species.

[0120] In some embodiments, the anti-CD40 antibody cross-reacts with at least one allelic variant of the CD40 protein (or a fragment thereof). In some embodiments, the allelic variant has up to 30 amino acid substitutions (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, or 30) compared to the naturally occurring CD40 protein (or a fragment thereof) (e.g., conserved substitutions). In some embodiments, the anti-CD40 antibody does not cross-react with any allelic variant of the CD40 protein (or a fragment thereof).

[0121] In some embodiments, the anti-CD40 antibody cross-reacts with at least one interspecies variant of the CD40 protein. In some embodiments, for example, the CD40 protein (or a fragment thereof) is human CD40, and the interspecies variant of the CD40 protein (or a fragment thereof) is a variant found in rhesus monkeys. In some embodiments, the anti-CD40 antibody does not cross-react with any interspecies variant of the CD40 protein.

[0122] In some embodiments, any anti-CD40 antibody as described herein includes an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the anti-CD40 antibody includes an IgG1 type heavy chain constant region. In some embodiments, the anti-CD40 antibody includes an IgG2 type heavy chain constant region. In some embodiments, the anti-CD40 antibody includes an IgG3 type heavy chain constant region. In some embodiments, the anti-CD40 antibody includes an IgG4 type heavy chain constant region. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:218. In some embodiments, the heavy chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:219. In some embodiments, the anti-CD40 antibody includes a κ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:220. In some embodiments, the anti-CD40 antibody includes a λ light chain constant region. In some embodiments, the light chain constant region comprises (including a sequence consisting of or substantially consisting of) the amino acid sequence SEQ ID NO:221. In some embodiments, the anti-CD40 antibody includes an antibody heavy chain variable domain and an antibody light chain variable domain.

[0123] In some embodiments, the anti-CD40 antibody includes a heavy chain variable domain (V H ), the V H Includes: a heavy chain complementarity determination region (HC-CDR)1 containing GYYWS (SEQ ID NO:1); HC-CDR2 containing X1IGGSSX2X3TX4YNPSLKS (SEQ ID NO:114), where X1 is A or F, X2 is G or S, X3 is S or T, and X4 is G or N; and HC-CDR3 containing QPX1X2X3RSX4FX5Y (SEQ ID NO:116), where X1 is A, N, or Q, X2 is A, F, Q, V, W, or Y, X3 is A or Y, X4 is A, G, P, Q, or S, and X5 is A, F, H, K, Q, V, or Y; and a light chain variable structural domain (V L ), the V LIt includes: a light chain complementarity determination region (LC-CDR)1, which includes KSSQSLLYX1X2NX3KNYLA (SEQ ID NO:118), wherein X1 is R, S or O, X2 is G, L, M, S, V or Y, and X3 is G, N or O; LC-CDR2, which includes WASTRES (SEQ ID NO:77); and LC-CDR3, which includes X1QYX2X3X4PT (SEQ ID NO:120), wherein X1 is A, G, M, Q or S, X2 is L, W or Y, X3 is A, G, H, S or V, and X4 is A, F, H, K, L, R, S, T, W or Y.

[0124] In some embodiments, the anti-CD40 antibody includes V H The V H It comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:5-9 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:29-47 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0125] In some embodiments, the anti-CD40 antibody includes V H The V H It includes: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:5-9; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:29-47.

[0126] In some embodiments, the anti-CD40 antibody includes V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-62 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:77 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:82-101 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0127] In some embodiments, the anti-CD40 antibody includes V L The V L It includes: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:54-62; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:77; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:82-101.

[0128] In some embodiments, the anti-CD40 antibody includes V H The V H Contains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:1 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising the amino acid sequence shown in any of SEQ ID NOs:5-9 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and HC-CDR3, comprising the amino acid sequence shown in any of SEQ ID NOs:29-47 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:54-62 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:77 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:82-101 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0129] In some embodiments, the anti-CD40 antibody includes V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:1; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:5-9; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:29-47; and V L The V LIt comprises: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:54-62; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:77; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:82-101.

[0130] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; HC-CDR3, which contains the amino acid sequence SEQ ID NO:29; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:82; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0131] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:29; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:82.

[0132] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; HC-CDR3, which contains the amino acid sequence SEQ ID NO:33; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:87; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0133] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:33; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:87.

[0134] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; HC-CDR3, which contains the amino acid sequence SEQ ID NO:33; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:57; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:89; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0135] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:7; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:33; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:57, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:89.

[0136] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; HC-CDR3, which contains the amino acid sequence SEQ ID NO:36; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:58; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:92; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0137] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:8; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:36; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:58, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:92.

[0138] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; HC-CDR3, which contains the amino acid sequence SEQ ID NO:29; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:60; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:97; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0139] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:29; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:60, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:97.

[0140] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; HC-CDR3, which contains the amino acid sequence SEQ ID NO:40; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:93; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0141] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:9; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:40; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:93.

[0142] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; HC-CDR3, which contains the amino acid sequence SEQ ID NO:40; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:98; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0143] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:40; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:98.

[0144] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; HC-CDR3, which contains the amino acid sequence SEQ ID NO:41; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and VL The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:97; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0145] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:41; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:54, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:97.

[0146] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; HC-CDR3, which contains the amino acid sequence SEQ ID NO:47; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:58; LC-CDR2, which contains the amino acid sequence SEQ ID NO:77; LC-CDR3, which contains the amino acid sequence SEQ ID NO:101; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0147] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:1; HC-CDR2, which contains the amino acid sequence SEQ ID NO:5; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:47; and VL The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:58, LC-CDR2, which contains the amino acid sequence SEQ ID NO:77, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:101.

[0148] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains any amino acid sequence of SEQ ID NOs:1, 5-9, and 29-47 or a variant thereof, said variant containing substitutions of up to about 5 amino acids; and V L The V L Contains any amino acid sequence from SEQ ID NOs:54-62,77,82-101 or a variant thereof, said variant containing substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains any amino acid sequence from SEQ ID NOs:1,5-9,29-47; and V L The V L It contains any of the amino acid sequences in SEQ ID NOs:54-62,77,82-101.

[0149] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 29, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:54, 77, and 82, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 29; and V L The V L It contains amino acid sequences SEQ ID NOs:54, 77 and 82.

[0150] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 33, or the V HVariants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:54, 77, and 87, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 33; and V L The V L It contains amino acid sequences SEQ ID NOs:54, 77 and 87.

[0151] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 7, and 33, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:57, 77, and 89, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 7, and 33; and V L The V L It contains amino acid sequences SEQ ID NOs:57, 77 and 89.

[0152] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 8, and 36, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:58, 77, and 92, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 8, and 36; and V L The V LIt contains amino acid sequences SEQ ID NOs:58, 77 and 92.

[0153] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 29, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:60, 77, and 97, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 29; and V L The V L It contains amino acid sequences SEQ ID NOs:60, 77 and 97.

[0154] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 9, and 40, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:54, 77, and 93, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 9, and 40; and V L The V L It contains amino acid sequences SEQ ID NOs:54, 77 and 93.

[0155] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 40, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:54, 77, and 98, or the V LVariants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 40; and V L The V L It contains amino acid sequences SEQ ID NOs:54, 77 and 98.

[0156] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 41, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:54, 77, and 97, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 41; and V L The V L It contains amino acid sequences SEQ ID NOs:54, 77 and 97.

[0157] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 47, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:58, 77, and 101, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:1, 5, and 47; and V L The V L It contains amino acid sequences SEQ ID NOs:58, 77 and 101.

[0158] In some embodiments, the anti-CD40 antibody comprises V H The V HV containing any of the amino acid sequences shown in SEQ ID NOs:122-143 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V L V containing any of the amino acid sequences shown in SEQ ID NOs:169-196 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0159] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:122. In some embodiments, the anti-CD40 antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:123. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:127. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:129. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:131. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:135. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:136. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:137. In some embodiments, the anti-CD40 antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:143.

[0160] In some embodiments, the anti-CD40 antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:169. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:170. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:177. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:179. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:182. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:187. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:189. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs from the amino acid sequence SEQ ID NO:190. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs from the amino acid sequence SEQ ID NO:191. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:196.

[0161] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:122. HIncludes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:169. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0162] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:123. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:170. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0163] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:127. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:177. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0164] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:129. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:179. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0165] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:131. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:182. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0166] In some embodiments, the anti-CD40 antibody comprises VH It contains V as shown in the amino acid sequence SEQ ID NO:123. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:187. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0167] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:135. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:189. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0168] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:136. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:190. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0169] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:137. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:191. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0170] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:143. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:196. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0171] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-143 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:122-143; and V L The V L The antibody comprises any of the amino acid sequences shown in SEQ ID NOs:169-196 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:169-196. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-143, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:169-196.

[0172] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:122 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:122; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:169 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:169. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:122, and V L The V L It contains the amino acid sequence SEQ ID NO:169.

[0173] In some embodiments, the anti-CD40 antibody comprises: VH The V H Contains the amino acid sequence SEQ ID NO:123 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:123; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:170 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:170. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:123, and V L The V L It contains the amino acid sequence SEQ ID NO:170.

[0174] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:127 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:127; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:177 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:177. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:127, and V L The V L It contains the amino acid sequence SEQ ID NO:177.

[0175] In some embodiments, the anti-CD40 antibody comprises: V H The V HContains the amino acid sequence SEQ ID NO:129 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:129; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:179 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:179. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:129, and V L The V L It contains the amino acid sequence SEQ ID NO:179.

[0176] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:131 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:131; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:182 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:182. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:131, and V L The V L It contains the amino acid sequence SEQ ID NO:182.

[0177] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:123 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:123; and V LThe V L The antibody comprises the amino acid sequence SEQ ID NO:187 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:187. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:123, and V L The V L It contains the amino acid sequence SEQ ID NO:187.

[0178] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:135 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:135; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:189 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:189. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:135, and V L The V L It contains the amino acid sequence SEQ ID NO:189.

[0179] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:136 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:136; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:190 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:190. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:136, and V L The V L It contains the amino acid sequence SEQ ID NO:190.

[0180] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:137 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:137; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:191 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:191. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:137, and V L The V L It contains the amino acid sequence SEQ ID NO:191.

[0181] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:143 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:143; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:196 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:196. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:143, and V L The V L It contains the amino acid sequence SEQ ID NO:196.

[0182] In some embodiments, the anti-CD40 antibody comprises a heavy chain variable domain (V H ), the V H Includes: a heavy chain complementarity determination region (HC-CDR)1 containing RYAMH (SEQ ID NO:2); HC-CDR2 containing X1IWFDGX2X3X4YYADSVKD (SEQ ID NO:115), wherein X1 is A or G, X2 is G, N or R, X3 is A, G, K, M, Q or S, and X4 is A, D, E, K, M, N, Q, R, S or V; and HC-CDR3 containing DYDX1GX2SX3YFDY (SEQ ID NO:117), wherein X1 is A or S, X2 is W or Y, and X3 is F or Y; and a light chain variable structural domain (V L ), the V L It includes: a light chain complementarity determination region (LC-CDR)1, which includes RASQX1IX2X3X4LX5 (SEQ ID NO:119), wherein X1 is G, I, R or Y, X2 is S or T, X3 is G, L, M or S, X4 is W or Y, and X5 is A or S; LC-CDR2, which includes YASNLES (SEQ ID NO:78); and LC-CDR3, which includes QQX1KX2YPLT (SEQ ID NO:121), wherein X1 is A, H, S or V, and X2 is K, L, M, R, S or T.

[0183] In some embodiments, the anti-CD40 antibody comprises V H The V HThe formulation comprises: HC-CDR1, which comprises the amino acid sequence shown in SEQ ID NO:2 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; HC-CDR2, which comprises the amino acid sequence shown in any of SEQ ID NOs:10-26 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and HC-CDR3, which comprises the amino acid sequence shown in any of SEQ ID NOs:48-51 or a variant thereof, the variant comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0184] In some embodiments, the anti-CD40 antibody comprises V H The V H It includes: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:2; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:10-26; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:48-51.

[0185] In some embodiments, the anti-CD40 antibody comprises V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:63-72 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:78 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:102-110 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2 or 3) amino acids.

[0186] In some embodiments, the anti-CD40 antibody comprises V L The V L It includes: LC-CDR1, which contains any of the amino acid sequences shown in SEQ ID NOs:63-72; LC-CDR2, which contains the amino acid sequence shown in SEQ ID NO:78; and LC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:102-110.

[0187] In some embodiments, the anti-CD40 antibody comprises V H The V HContains: HC-CDR1, comprising the amino acid sequence shown in SEQ ID NO:2 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:10-26 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:48-51 or a variant thereof, the variant comprising substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:63-72 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:78 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3); and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:102-110 or variants thereof, the variants comprising substitutions of up to about 3 amino acids (e.g., 1, 2 or 3).

[0188] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence shown in SEQ ID NO:2; HC-CDR2, which contains any of the amino acid sequences shown in SEQ ID NOs:10-26; and HC-CDR3, which contains any of the amino acid sequences shown in SEQ ID NOs:48-51; and V L The V L It comprises: LC-CDR1, which comprises any of the amino acid sequences shown in SEQ ID NOs:63-72; LC-CDR2, which comprises the amino acid sequence shown in SEQ ID NO:78; and LC-CDR3, which comprises any of the amino acid sequences shown in SEQ ID NOs:102-110.

[0189] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V HVariants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:102; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0190] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102.

[0191] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:103; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0192] In some embodiments, the anti-CD40 antibody comprises V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:103.

[0193] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:64; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:102; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0194] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:11; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:64; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102.

[0195] In some embodiments, the anti-CD40 antibody comprises V H The V HContains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:49; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:104; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0196] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:49; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:104.

[0197] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:51; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:104; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0198] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:51; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:104.

[0199] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:66; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:102; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0200] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:14; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:66, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102.

[0201] In some embodiments, the anti-CD40 antibody comprises V H The VH Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:106; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0202] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:63, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:106.

[0203] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; HC-CDR3, which contains the amino acid sequence SEQ ID NO:50; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:67; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:107; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0204] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:15; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:50; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:67, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:107.

[0205] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:21; HC-CDR3, which contains the amino acid sequence SEQ ID NO:50; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:64; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:102; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0206] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:21; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:50; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:64; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102.

[0207] In some embodiments, the anti-CD40 antibody comprises: VH The V H Contains any amino acid sequence from SEQ ID NOs:2,10-26,48-51 or a variant thereof, said variant comprising substitutions of up to about 5 amino acids; and V L The V L Contains any amino acid sequence from SEQ ID NOs:63-72,78,102-110 or a variant thereof, said variant containing substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains any amino acid sequence from SEQ ID NOs:2,10-26,48-51; and V L The V L It contains any of the amino acid sequences in SEQ ID NOs:63-72,78,102-110.

[0208] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:63, 78, and 102, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48; and V L The V L It contains amino acid sequences SEQ ID NOs:63, 78 and 102.

[0209] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:63, 78, and 103, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The VH Contains amino acid sequences SEQ ID NOs:2, 10, and 48; and V L The V L It contains amino acid sequences SEQ ID NOs:63, 78 and 103.

[0210] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 11, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:64, 78, and 102, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 11, and 48; and V L The V L It contains amino acid sequences SEQ ID NOs:64, 78 and 102.

[0211] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 49, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:63, 78, and 104, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 49; and V L The V L It contains amino acid sequences SEQ ID NOs:63, 78 and 104.

[0212] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 51, or the V HVariants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:63, 78, and 104, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 51; and V L The V L It contains amino acid sequences SEQ ID NOs:63, 78 and 104.

[0213] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 14, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:66, 78, and 102, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 14, and 48; and V L The V L It contains the amino acid sequences SEQ ID NOs:66, 78 and 102.

[0214] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:63, 78, and 106, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48; and V L The V LIt contains amino acid sequences SEQ ID NOs:63, 78 and 106.

[0215] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 15, and 50, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:67, 78, and 107, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 15, and 50; and V L The V L It contains amino acid sequences SEQ ID NOs:67, 78 and 107.

[0216] In some embodiments, the anti-CD40 antibody includes V H The V H Contains amino acid sequences SEQ ID NOs:2, 21, and 50, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:64, 78, and 102, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody includes V [a specific antibody]. H The V H Contains amino acid sequences SEQ ID NOs:2, 21, and 50; and V L The V L It contains amino acid sequences SEQ ID NOs:64, 78 and 102.

[0217] In some embodiments, the anti-CD40 antibody comprises V H The V H V containing any of the amino acid sequences shown in SEQ ID NOs:144-166 H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L The V LV containing any of the amino acid sequences shown in SEQ ID NOs:197-213 L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0218] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:144. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:145. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:146. In some embodiments, the anti-CD40 antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:148. In some embodiments, the anti-CD40 antibody contains V H The V H It contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:150. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:151. In some embodiments, the anti-CD40 antibody contains V H The V H Contains one, two, or three HC-CDRs from the amino acid sequence SEQ ID NO:152. In some embodiments, the anti-CD40 antibody contains V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:160.

[0219] In some embodiments, the anti-CD40 antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:197. In some embodiments, the anti-CD40 antibody contains V L The V LContains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:198. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:199. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs from the amino acid sequence SEQ ID NO:200. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:202. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:204. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:205. In some embodiments, the anti-CD40 antibody contains V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:206.

[0220] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:197. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0221] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:198. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0222] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:199. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0223] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:146. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:200. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0224] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:148. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:202. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0225] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:150. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:202. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0226] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:151. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:204. LIt includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0227] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:145. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:205. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0228] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:152. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:206. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0229] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:160. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:200. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0230] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:144-166 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:144-166; and V L The V LThe antibody comprises any of the amino acid sequences shown in SEQ ID NOs:197-213 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:197-213. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains any of the amino acid sequences shown in SEQ ID NOs:144-166, and V L The V L It contains any of the amino acid sequences shown in SEQ ID NOs:197-213.

[0231] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:144 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:144; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:197 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:197. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:144, and V L The V L It contains the amino acid sequence SEQ ID NO:197.

[0232] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:145; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:198 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:198. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:145, and V L The V L It contains the amino acid sequence SEQ ID NO:198.

[0233] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:145; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:199 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:199. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:145, and V L The V L It contains the amino acid sequence SEQ ID NO:199.

[0234] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:146 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:146; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:200 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:200. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:146, and V L The V L It contains the amino acid sequence SEQ ID NO:200.

[0235] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:148 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:148; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:202 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:202. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:148, and V L The V L It contains the amino acid sequence SEQ ID NO:202.

[0236] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:150 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:150; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:202 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:202. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:150, and V L The V L It contains the amino acid sequence SEQ ID NO:202.

[0237] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:151 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:151; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:204 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:204. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:151, and V L The V L It contains the amino acid sequence SEQ ID NO:204.

[0238] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:145 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:145; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:205 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:205. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:145, and V L The V L It contains the amino acid sequence SEQ ID NO:205.

[0239] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:152 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:152; and V L The V L The antibody comprises the amino acid sequence SEQ ID NO:206 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:206. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:152, and V L The V L It contains the amino acid sequence SEQ ID NO:206.

[0240] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:160 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:160; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:200 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:200. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:160, and V L The V L It contains the amino acid sequence SEQ ID NO:200.

[0241] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:73; LC-CDR2, which contains the amino acid sequence SEQ ID NO:78; LC-CDR3, which contains the amino acid sequence SEQ ID NO:102; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0242] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:73, LC-CDR2, which contains the amino acid sequence SEQ ID NO:78, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:102.

[0243] In some embodiments, the anti-CD40 antibody comprises: V H The V HContains amino acid sequences SEQ ID NOs:2, 10, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:73, 78, and 102, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48; and V L The V L It contains the amino acid sequences SEQ ID NOs:73, 78 and 102.

[0244] In some embodiments, the anti-CD40 antibody comprises V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:144.

[0245] In some embodiments, the anti-CD40 antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:214.

[0246] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:214. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0247] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:144 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:144; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:214 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:214. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:144, and V L The V L It contains the amino acid sequence SEQ ID NO:214.

[0248] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:74; LC-CDR2, which contains the amino acid sequence SEQ ID NO:79; LC-CDR3, which contains the amino acid sequence SEQ ID NO:111; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0249] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:2; HC-CDR2, which contains the amino acid sequence SEQ ID NO:10; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:48; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:74; LC-CDR2, which contains the amino acid sequence SEQ ID NO:79; and LC-CDR3, which contains the amino acid sequence SEQ ID NO:111.

[0250] In some embodiments, the anti-CD40 antibody comprises: V H The V HContains amino acid sequences SEQ ID NOs:2, 10, and 48, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:74, 79, and 111, or the V L Variants of [the antibody], wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains amino acid sequences SEQ ID NOs:2, 10, and 48; and V L The V L It contains amino acid sequences SEQ ID NOs:74, 79 and 111.

[0251] In some embodiments, the anti-CD40 antibody comprises V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:144.

[0252] In some embodiments, the anti-CD40 antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:215.

[0253] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:144. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:215. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0254] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:144 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:144; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:215 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:215. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:144, and V L The V L It contains the amino acid sequence SEQ ID NO:215.

[0255] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:27; HC-CDR3, which contains the amino acid sequence SEQ ID NO:52; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:75; LC-CDR2, which contains the amino acid sequence SEQ ID NO:80; LC-CDR3, which contains the amino acid sequence SEQ ID NO:112; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0256] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:3; HC-CDR2, which contains the amino acid sequence SEQ ID NO:27; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:52; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:75, LC-CDR2, which contains the amino acid sequence SEQ ID NO:80, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:112.

[0257] In some embodiments, the anti-CD40 antibody comprises V H The V HContains amino acid sequences SEQ ID NOs:3, 27, and 52, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:75, 80, and 112, or the V L Variants of the antibody, wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody contains V H The V H Contains amino acid sequences SEQ ID NOs:3, 27, and 52; and V L The V L It contains the amino acid sequences SEQ ID NOs:75, 80 and 112.

[0258] In some embodiments, the anti-CD40 antibody comprises V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:167.

[0259] In some embodiments, the anti-CD40 antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:216.

[0260] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:167. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:216. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0261] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:167 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:167; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:216 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:216. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:167, and V L The V L It contains the amino acid sequence SEQ ID NO:216.

[0262] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:28; HC-CDR3, which contains the amino acid sequence SEQ ID NO:53; or the V H Variants of which contain up to about 5 amino acid substitutions in their HC-CDRs; and V L The V L Contains: LC-CDR1, which contains the amino acid sequence SEQ ID NO:76; LC-CDR2, which contains the amino acid sequence SEQ ID NO:81; LC-CDR3, which contains the amino acid sequence SEQ ID NO:113; or the V L Variants of which contain up to about 5 amino acid substitutions in their LC-CDRs.

[0263] In some embodiments, the anti-CD40 antibody comprises V H The V H Contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO:4; HC-CDR2, which contains the amino acid sequence SEQ ID NO:28; and HC-CDR3, which contains the amino acid sequence SEQ ID NO:53; and V L The V L It includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO:76, LC-CDR2, which contains the amino acid sequence SEQ ID NO:81, and LC-CDR3, which contains the amino acid sequence SEQ ID NO:113.

[0264] In some embodiments, the anti-CD40 antibody comprises V H The V HContains amino acid sequences SEQ ID NOs:4, 28, and 53, or the V H Variants containing substitutions of up to about 5 amino acids; and V L The V L Contains amino acid sequences SEQ ID NOs:76, 81, and 113, or the V L Variants of the antibody, wherein the variants contain substitutions of up to about 5 amino acids. In some embodiments, the anti-CD40 antibody contains V H The V H Contains amino acid sequences SEQ ID NOs:4, 28, and 53; and V L The V L It contains amino acid sequences SEQ ID NOs:76, 81 and 113.

[0265] In some embodiments, the anti-CD40 antibody comprises V H The V H It contains one, two, or three HC-CDRs of the amino acid sequence SEQ ID NO:168.

[0266] In some embodiments, the anti-CD40 antibody comprises V L The V L Contains one, two, or three LC-CDRs of the amino acid sequence SEQ ID NO:217.

[0267] In some embodiments, the anti-CD40 antibody comprises V H It contains V as shown in the amino acid sequence SEQ ID NO:168. H Includes HC-CDR1, HC-CDR2, and HC-CDR3; and V L It contains V as shown in the amino acid sequence SEQ ID NO:217. L It includes LC-CDR1, LC-CDR2 and LC-CDR3.

[0268] In some embodiments, the anti-CD40 antibody comprises: V H The V H Contains the amino acid sequence SEQ ID NO:168 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:168; and V L The V LThe antibody comprises the amino acid sequence SEQ ID NO:217 or a variant thereof, said variant having at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with the amino acid sequence SEQ ID NO:217. In some embodiments, the anti-CD40 antibody comprises V H The V H Contains the amino acid sequence SEQ ID NO:168, and V L The V L It contains the amino acid sequence SEQ ID NO:217.

[0269] In some embodiments, functional epitopes can be resolved using a combined alanine scanning technique. In this process, the combined alanine scanning technique can be used to identify amino acids in the CD40 protein essential for interaction with anti-CD40 antibodies. In some embodiments, the epitope is conformational, and the epitope can also be identified using the crystal structure of an anti-CD40 antibody that binds to the CD40 protein.

[0270] In some embodiments, this application provides an antibody that competitively binds to CD40 with any of the anti-CD40 antibodies described herein. In some embodiments, an antibody capable of competitively binding to an epitope on CD40 with any of the anti-CD40 antibodies described herein is provided. In some embodiments, an anti-CD40 antibody is provided that contains V H and V L The anti-CD40 antibody molecule binds to the same epitope, wherein the V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-168, and the V L Contains any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, an anti-CD40 antibody is provided, which, together with V H and V L The anti-CD40 antibody competitively binds to CD40, wherein the V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-168, and the V L It contains any of the amino acid sequences shown in SEQ ID NOs:169-217.

[0271] In some embodiments, a competition assay can be used to identify monoclonal antibodies that competitively bind to CD40 with the anti-CD40 antibody described herein. A competition assay can determine whether two antibodies bind to the same epitope by identifying identical or spatially overlapping epitopes or by one antibody competitively inhibiting the binding of another antibody to the antigen. In some embodiments, such a competing antibody binds to the same epitope as the antibody described herein. Some exemplary competition assays include, but are not limited to, conventional assays as described in Harlow and Lane (1988) Antibodies: A Laboratory Manual ch. 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, NY). Detailed exemplary methods for resolving antibody-bound epitopes are described in Morris (1996) "Epitope Mapping Protocols," in Methods in Molecular Biology vol. 66 (Humana Press, Totowa, NJ). In some embodiments, if each antibody blocks 50% or more of the binding of another antibody, they are said to bind to the same epitope. In some embodiments, the antibody competing with the anti-CD40 antibody described herein is a chimeric antibody, a humanized antibody, or a fully human antibody.

[0272] Exemplary anti-CD40 antibody sequences are shown in Tables 2 and 3, where CDRs are numbered according to the Kabat definition. Those skilled in the art will recognize that various known algorithms (Kabat definition) exist for predicting CDR locations and defining the variable regions of the antibody light and heavy chains. CDRs containing antibodies as described herein, V H and / or V L Sequences, but antibodies based on prediction algorithms rather than those exemplified in the table below are also within the scope of this application.

[0273] Table 2. Exemplary anti-CD40 antibody CDR sequences

[0274]

[0275]

[0276]

[0277]

[0278]

[0279]

[0280]

[0281] Table 3 Exemplary Sequences

[0282]

[0283]

[0284]

[0285]

[0286]

[0287]

[0288] CD40

[0289] CD40 is a 45-50 kDa type I membrane protein and a member of the TNFR superfamily. CD40 is expressed not only on antigen-presenting cells (such as B cells, dendritic cells (DCs), macrophages, and monocytes), but also on non-immune cells, such as epithelial, endothelial, and stromal cells (fibroblasts, myofibroblasts, synovial cells, stellate cells, etc.), platelets, and tumor cells. U, and P Libby. Cellular and Molecular Life Sciences: CMLS vol. 58, 1(2001): 4-43). CD40, as a transmembrane signal transducer, leads to the activation of intracellular kinases and transcription factors within the cell, participating in the regulation of a wide range of molecular and cellular processes, including the initiation and development of cellular and humoral adaptive immunity. Because the intracellular region of CD40 lacks intrinsic kinase activity, its signaling is primarily transduced through ligand-dependent recruitment of adaptor proteins from the TNF receptor-associated factor (TRAF) family. TRAF not only couples CD40 to intracellular signal transduction components but also triggers the dissociation of this signaling complex from CD40 and its release into the cytoplasm, where it activates proximal protein kinases as an E3 ubiquitin ligase. It can activate the mitogen-activated protein kinase (MAPK) pathway, including extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38MAPK, phosphatidylinositol 3-kinase (PI3K) cascade, transcription factor nuclear factor-κB (NF-κB), and signal transduction and transcription activator (STAT) (Loskog, Angelica SI, and Aristides G Eliopoulos. Seminars in immunology vol. 21, 5(2009): 301-7; and Matsuzawa, Atsushi et al. Science (New York, NY) vol. 321, 5889(2008): 663-8). These pathways work synergistically to regulate CD40 activity in a cell type and microenvironment-dependent manner.

[0290] The interaction between CD40 and CD40L triggers a variety of immune responses, including the expression of cellular stress-related genes and B cell activation (immunoglobulin class switching, germinal center formation, and cytokine production) (Belkhir, Re et al. Scandinavian journal of immunology vol. 79, 1(2014): 37-42; and Bensinger, William et al. British journal of haematology vol. 159, 1(2012): 58-66). The CD40-CD40L interaction also plays a crucial role in T cell activation and the upregulation of inflammatory response-related surface molecules and cytokines in chronic inflammatory diseases. These cytokines include interleukin (IL)-2, IL-12, TNF-α, interferon (IFN)-α, and IL-1 and IL-6 (Sidiropoulos, PI, and DT Boumpas. Lupus vol. 13, 5(2004): 391-7).

[0291] Given the important role of CD40–CD40L as a co-stimulatory molecule between B cells and T cells, there has been interest in the role of CD40–CD40L antagonists in inflammatory or autoimmune diseases such as psoriasis, lupus nephritis, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), diabetes, and immune rejection.

[0292] CD40L

[0293] CD40L is a 32-39 kDa type II transmembrane protein and a member of the TNF ligand superfamily (TNFSF, including TNF, lymphotoxin, CD27L, CD30L, and FasL). CD40L is generated by activated CD4+. + CD40L is expressed on T cells, activated B cells, and platelets, but under inflammatory conditions, it can also be induced to be expressed in monocytes, natural killer cells, mast cells, and basophils (Elgueta, Raul et al. Immunological reviews vol.229,1(2009):152-72). The soluble form of CD40L (sCD40L) has been reported to exhibit similar biological activity to the transmembrane form, triggering the CD40L / CD40 signaling cascade.

[0294] Therefore, neutralizing the binding of CD40 and CD40L could be a method for treating diseases and symptoms mediated by the CD40-CD40L pathway.

[0295] Full-length anti-CD40 antibody

[0296] In some embodiments, the anti-CD40 antibody is a full-length anti-CD40 antibody. In some embodiments, the full-length anti-CD40 antibody is IgA, IgD, IgE, IgG, or IgM. In some embodiments, the full-length anti-CD40 antibody includes a constant IgG region, such as a constant region of IgG1, IgG2, IgG3, IgG4, or a variant thereof. In some embodiments, the full-length anti-CD40 antibody includes a λ light chain constant region. In some embodiments, the full-length anti-CD40 antibody includes a κ light chain constant region. In some embodiments, the full-length anti-CD40 antibody is a full-length human anti-CD40 antibody. In some embodiments, the full-length anti-CD40 antibody includes a mouse immunoglobulin Fc sequence. In some embodiments, the full-length anti-CD40 antibody includes an altered or otherwise modified Fc sequence such that it has enhanced effector functions of antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

[0297] Therefore, for example, in some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, the anti-CD40 antibody specifically binding to CD40. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0298] In some embodiments, a full-length anti-CD40 antibody comprising an IgG2 constant region is provided, the anti-CD40 antibody specifically binding to CD40. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0299] In some embodiments, a full-length anti-CD40 antibody comprising an IgG3 constant region is provided, the anti-CD40 antibody specifically binding to CD40. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0300] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, the anti-CD40 antibody specifically binding to CD40. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0301] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-4 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:5-28 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-28 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 ...; and b) a light chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53; and b) a light chain variable domain comprising: HC-CDR1, comprising any The amino acid sequences or variants thereof shown in SEQ ID NOs:54-76, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains amino acid sequences or variants thereof shown in SEQ ID NOs:77-81, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences or variants thereof shown in SEQ ID NOs:82-113, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0302] In some embodiments, a full-length anti-CD40 antibody comprising an IgG2 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-4 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:5-28 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-28 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 or variants thereof, the heavy chain variable domain comprising: HC-CDR2 ...; and b) a light chain variable domain comprising: HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53; and b) a light chain variable domain comprising: HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53; and b) a light chain variable domain comprising: HC-CDR2, comprising any of The amino acid sequences shown in SEQ ID NOs:54-76 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences shown in SEQ ID NOs:77-81 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences shown in SEQ ID NOs:82-113 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0303] In some embodiments, a full-length anti-CD40 antibody comprising an IgG3 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-4 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:5-28 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1 comprising SEQ ID NOs:1-28 or variants thereof, the heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 ... The amino acid sequences shown in SEQ ID NOs:54-76 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); LC-CDR2, which contains amino acid sequences shown in SEQ ID NOs:77-81 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3); and LC-CDR3, which contains amino acid sequences shown in SEQ ID NOs:82-113 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0304] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:1-4 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; HC-CDR2, comprising any of the amino acid sequences shown in SEQ ID NOs:5-28 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and HC-CDR3, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 or variants thereof, the variants comprising substitutions of up to about 3 (e.g., 1, 2, or 3) amino acids; and b) a light chain variable domain comprising: LC-CDR1, comprising SEQ ID NOs:1-28 or variants thereof, the heavy chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53 ...; and b) a light chain variable domain comprising: HC-CDR1, comprising any of the amino acid sequences shown in SEQ ID NOs:29-53; and b) a light chain variable domain comprising: HC-CDR1, comprising any The amino acid sequences shown in SEQ ID NOs:54-76 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), LC-CDR2, which contains the amino acid sequences shown in SEQ ID NOs:77-81 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3), and LC-CDR3, which contains the amino acid sequences shown in SEQ ID NOs:82-113 or variants thereof, wherein the variants contain substitutions of up to about 3 amino acids (e.g., 1, 2, or 3). In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0305] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-4, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-28, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 29-53, or a variant of the heavy chain variable domain comprising a substitution of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its HC-CDR sequence; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-76, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 77-81, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-76, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 57-81, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-76 ... The amino acid sequence represented by NOs:82-113, or a variant of the light chain variable domain, contains substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its LC-CDR sequence. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0306] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 1-4, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 5-28, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 29-53, or a variant of the heavy chain variable domain having an HC-CDR sequence comprising up to about 5 (e.g., 1, 2, 3, 4, or 5) amino acid substitutions; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-76, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs: 77-81, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs: 54-76, and HC ... The amino acid sequence represented by NOs:82-113, or a variant of the light chain variable domain, contains substitutions of up to about 5 amino acids (e.g., 1, 2, 3, 4, or 5) in its LC-CDR sequence. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0307] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-4, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:5-28, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:29-53; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:54-76, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:77-81, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:82-113. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0308] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:1-4, HC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:5-28, and HC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:29-53; and b) a light chain variable domain comprising: LC-CDR1 comprising any of the amino acid sequences shown in SEQ ID NOs:54-76, LC-CDR2 comprising any of the amino acid sequences shown in SEQ ID NOs:77-81, and LC-CDR3 comprising any of the amino acid sequences shown in SEQ ID NOs:82-113. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0309] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising amino acid sequence SEQ ID NO:29; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:54, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:82. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0310] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising amino acid sequence SEQ ID NO:33; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:54, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:87. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0311] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:33; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:57, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:89. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0312] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising amino acid sequence SEQ ID NO:36; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:58, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:92. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0313] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising amino acid sequence SEQ ID NO:29; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:60, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:97. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0314] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:40; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:93. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0315] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising amino acid sequence SEQ ID NO:40; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:54, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:98. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0316] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising amino acid sequence SEQ ID NO:41; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:54, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:97. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0317] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:47; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:58, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:101. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0318] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0319] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:103. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0320] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:11, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:64, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0321] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:49; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:104. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0322] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:51; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:104. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0323] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:14, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:66, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0324] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:106. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0325] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:15, and HC-CDR3 comprising amino acid sequence SEQ ID NO:50; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:67, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:107. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0326] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:21, and HC-CDR3 comprising amino acid sequence SEQ ID NO:50; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:64, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0327] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:73, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0328] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:74, LC-CDR2 comprising amino acid sequence SEQ ID NO:79, and LC-CDR3 comprising amino acid sequence SEQ ID NO:111. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0329] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:3, HC-CDR2 comprising amino acid sequence SEQ ID NO:27, and HC-CDR3 comprising amino acid sequence SEQ ID NO:52; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:75, LC-CDR2 comprising amino acid sequence SEQ ID NO:80, and LC-CDR3 comprising amino acid sequence SEQ ID NO:112. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0330] In some embodiments, a full-length anti-CD40 antibody comprising a constant region of IgG1 is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:4, HC-CDR2 comprising amino acid sequence SEQ ID NO:28, and HC-CDR3 comprising amino acid sequence SEQ ID NO:53; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:76, LC-CDR2 comprising amino acid sequence SEQ ID NO:81, and LC-CDR3 comprising amino acid sequence SEQ ID NO:113. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0331] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:29; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:82. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0332] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:33; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:87. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0333] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:7, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:33; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:57, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:89. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0334] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:8, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:36; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:58, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:92. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0335] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:29; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:60, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:97. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0336] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:1, HC-CDR2 comprising amino acid sequence SEQ ID NO:9, and HC-CDR3 comprising amino acid sequence SEQ ID NO:40; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:54, LC-CDR2 comprising amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising amino acid sequence SEQ ID NO:93. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0337] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:40; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:98. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0338] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:41; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:54, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:97. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0339] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:1, HC-CDR2 comprising the amino acid sequence SEQ ID NO:5, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:47; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:58, LC-CDR2 comprising the amino acid sequence SEQ ID NO:77, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:101. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0340] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0341] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:103. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0342] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:11, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:64, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0343] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:49; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:104. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0344] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:51; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:104. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0345] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:14, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:66, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0346] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:63, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:106. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0347] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:15, and HC-CDR3 comprising amino acid sequence SEQ ID NO:50; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:67, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:107. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0348] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:21, and HC-CDR3 comprising amino acid sequence SEQ ID NO:50; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:64, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0349] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising amino acid sequence SEQ ID NO:2, HC-CDR2 comprising amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising amino acid sequence SEQ ID NO:73, LC-CDR2 comprising amino acid sequence SEQ ID NO:78, and LC-CDR3 comprising amino acid sequence SEQ ID NO:102. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0350] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:2, HC-CDR2 comprising the amino acid sequence SEQ ID NO:10, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:48; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:74, LC-CDR2 comprising the amino acid sequence SEQ ID NO:79, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:111. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0351] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:3, HC-CDR2 comprising the amino acid sequence SEQ ID NO:27, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:52; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:75, LC-CDR2 comprising the amino acid sequence SEQ ID NO:80, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:112. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0352] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a) a heavy chain variable domain comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO:4, HC-CDR2 comprising the amino acid sequence SEQ ID NO:28, and HC-CDR3 comprising the amino acid sequence SEQ ID NO:53; and b) a light chain variable domain comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO:76, LC-CDR2 comprising the amino acid sequence SEQ ID NO:81, and LC-CDR3 comprising the amino acid sequence SEQ ID NO:113. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0353] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-168 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:122-168; and a light chain variable domain (V L ), the V LThe IgG1 comprises any of the amino acid sequences shown in SEQ ID NOs:169-217 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0354] In some embodiments, a full-length anti-CD40 antibody comprising an IgG2 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-168 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:122-168; and a light chain variable domain (V L ), the V L The IgG2 comprises any of the amino acid sequences shown in SEQ ID NOs:169-217 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, the IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0355] In some embodiments, a full-length anti-CD40 antibody comprising an IgG3 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the VH Contains any of the amino acid sequences shown in SEQ ID NOs:122-168 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:122-168; and a light chain variable domain (V L ), the V L The IgG3 comprises any of the amino acid sequences shown in SEQ ID NOs:169-217 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, the IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0356] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-168 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:122-168; and a light chain variable domain (V L ), the V LThe IgG4 comprises any of the amino acid sequences shown in SEQ ID NOs:169-217 or variants thereof, wherein the variants have at least about 90% (e.g., at least 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99%) sequence identity with any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0357] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V H Contains any of the amino acid sequences shown in SEQ ID NOs:122-168, and a light chain variable domain (V L ), the V L It comprises any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0358] In some embodiments, a full-length anti-CD40 antibody comprising an IgG4 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain (V H ), the V HContains any of the amino acid sequences shown in SEQ ID NOs:122-168, and a light chain variable domain (V L ), the V L The IgG4 comprises any of the amino acid sequences shown in SEQ ID NOs:169-217. In some embodiments, the IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:219 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0359] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:122, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:169. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0360] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:123, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:170. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0361] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:127, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:177. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0362] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:129, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:179. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0363] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:131, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:182. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0364] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:123, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:187. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0365] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:135, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:189. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0366] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:136, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:190. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0367] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:137, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:191. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0368] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:143, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:19. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0369] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:144, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:197. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0370] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:145, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:198. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0371] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:145, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:199. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0372] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:146, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:200. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0373] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:148, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:202. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0374] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:150, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:202. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0375] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:151, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:204. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0376] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:145, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:205. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0377] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:152, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:206. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0378] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:160, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:200. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0379] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:144, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:214. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0380] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:144, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:215. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218 and the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221.

[0381] In some embodiments, a full-length anti-CD40 antibody comprising an IgG1 constant region is provided, wherein the anti-CD40 antibody comprises: a heavy chain variable domain comprising the amino acid sequence SEQ ID NO:167, and a light chain variable domain comprising the amino acid sequence SEQ ID NO:216. In some embodiments, the IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:218. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:220. In some embodiments, the light chain constant region comprises or is composed of the amino acid sequence SEQ ID NO:221. In some embodiments, the heavy chain constant region...

Claims

1. An isolated anti-CD40 antibody, comprising: V H The V H Contains: HC-CDR1, with the amino acid sequence SEQ ID NO: 1; HC-CDR2, with the amino acid sequence SEQ ID NO: 7; and HC-CDR3, with the amino acid sequence SEQ ID NO: 33; and V L The V L It includes: LC-CDR1, whose amino acid sequence is SEQ ID NO: 57, LC-CDR2, whose amino acid sequence is SEQ ID NO: 77, and LC-CDR3, whose amino acid sequence is SEQ ID NO:

89.

2. The isolated anti-CD40 antibody according to claim 1, comprising: V H Its amino acid sequence is SEQ ID NO: 129 or a variant thereof, said variant having at least 90% sequence identity with the amino acid sequence SEQ ID NO: 129; and V L The amino acid sequence is SEQ ID NO: 179 or a variant thereof, which has at least 90% sequence identity with the amino acid sequence SEQ ID NO:

179.

3. The anti-CD40 antibody isolated according to claim 1, wherein the anti-CD40 antibody comprises an Fc fragment.

4. The anti-CD40 antibody isolated according to claim 3, wherein the anti-CD40 antibody is a full-length IgG antibody.

5. The anti-CD40 antibody isolated according to claim 4, wherein the anti-CD40 antibody is a full-length IgG1 or IgG4 antibody.

6. The anti-CD40 antibody isolated according to any one of claims 1-5, wherein the anti-CD40 antibody is a chimeric, humanized, or fully human antibody.

7. The anti-CD40 antibody isolated according to any one of claims 1-2, wherein the anti-CD40 antibody is an antigen-binding fragment selected from Fab, Fab', F(ab)'2, Fab'-SH, single-chain antibody (scFv), Fv fragment, dAb, or double-chain antibody (diabody).

8. An isolated nucleic acid molecule encoding the anti-CD40 antibody according to any one of claims 1-7.

9. A carrier comprising the nucleic acid molecule of claim 8.

10. An isolated host cell comprising the anti-CD40 antibody of any one of claims 1-7, the nucleic acid molecule of claim 8, or the vector of claim 9.

11. A method for preparing anti-CD40 antibody, comprising: a) Culture the host cells as described in claim 10 under conditions that enable effective expression of anti-CD40 antibodies; and b) Obtain the expressed anti-CD40 antibody from the host cell.

12. A pharmaceutical composition comprising an antiCD40 antibody according to any one of claims 1-7 and a pharmaceutically acceptable carrier, said pharmaceutical composition for treating a desired individual disease or condition.

13. The use of any one of the anti-CD40 antibody of claims 1-7, the nucleic acid molecule of claim 8, the vector of claim 9, the isolated host cell of claim 10, the antibody prepared by the method of claim 11, or the pharmaceutical composition of claim 12 in the preparation of a medicament for treating a desired individual disease or condition, wherein the disease or condition is rheumatoid arthritis or Sjogren's disease.

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