TW202334235A - Antibodies specifically recognizing fasl and uses thereof - Google Patents

Abstract

The present disclosure provides antibodies or antigen-binding fragments specifically recognizing FasL, and manufacturing methods and uses thereof.

Description

Antibodies that specifically recognize FasL and their applications

The present invention relates to antibodies or antigen-binding fragments that specifically recognize FasL, as well as preparation methods and uses thereof.

FasL (CD95L) is a transmembrane protein and a pro-apoptotic member of the tumor necrosis factor (TNF) superfamily. The extracellular domain of FasL contains a ligand dimer and receptor binding domain (TNF homology domain, THD), while the intracellular domain of FasL is involved in a variety of signaling pathways, especially as a T cell receptor co-factor during T cell activation. Stimulatory molecules (Calmon-Hamaty, Flavia et al. Cytokine vol. 75,2 (2015): 228-33.). The intracellular part of FasL contains an extended polyproline region that can interact with proteins with proline-binding motifs, such as Src homology 3 (SH3) and WW domains (Wenzel, J et al. FEBS letters vol. 509,2 (2001): 255-62.; Blott, E J et al. Journal of cell science vol. 114,Pt 13 (2001): 2405-16.). In addition, there are several tyrosine phosphorylation sites and a "dual" casein kinase phosphorylation motif. FasL protein has two forms: membrane-bound protein and soluble protein. The soluble form is produced by alternative splicing or proteolysis of the membrane-bound form. Under physiological conditions, FasL expression is tightly controlled and restricted in cells of the innate and adaptive immune systems and in immune-privileged sites such as the eye, placenta, or testes (Stenqvist, Ann-Christin et al. Journal of immunology (Baltimore, Md. : 1950) vol. 191,11 (2013): 5515-23.). FasL is expressed on the surface of two major immune effector cells, namely activated T cells and natural killer (NK) cells, but is also expressed on the surface of macrophages, neutrophils and dendritic cells (Kiener, P A et al . The Journal of experimental medicine vol. 185,8 (1997): 1511-6.; Liles, W C et al. The Journal of experimental medicine vol. 184,2 (1996): 429-40. doi:10.1084/jem. 184.2.429.). The expression of FasL can be induced by TCR (T cell receptor) activation, or its expression can be regulated by transcription after stimulation by cytokines, especially interferon (INF) (Tsutsui, H et al. Journal of immunology ( Baltimore, Md.: 1950) vol. 157,9 (1996): 3967-73.).

Fas receptor (CD95/APO-1) is a member of the TNF receptor superfamily. Fas protein has two forms: membrane-bound protein and soluble protein. Fas mainly exists in membrane-bound form. The soluble Fas protein lacks a transmembrane domain and cannot interact with FasL to induce apoptosis. Therefore, it plays a regulatory role in apoptosis, such as inhibiting apoptosis induced by membrane-bound Fas (mFas) (Jee, Youngheun et al. al. Journal of veterinary science vol. 11,2 (2010): 115-9.). The extracellular domain of mFas protein contains three cysteine-rich domains (CRDs), which are structural features of the TNF receptor family (Zhang, Gongyi. Current opinion in structural biology vol. 14,2 (2004) : 154-60.). The C-terminus of the intracellular domain of Fas protein contains a death domain (DD), which is required for the induction of apoptosis and is characteristic of this subset of death receptors (Chan, F K et al. Science (New York) , N.Y.) vol. 288,5475 (2000): 2351-4.). Fas is expressed in multiple organs and tissues, especially in peripheral blood T and B lymphocytes, NK cells, monocytes, fibroblasts, endothelial cells, epithelial cells, etc. (Wang, Mei, and Ping Su. Systems biology in reproductive medicine vol. 64,2 (2018): 93-102.).

In the Fas-mediated apoptotic pathway, the binding of FasL drives Fas aggregation and the binding of Fas to Fas-binding protein (FADD). FADD recruits caspase-8 and caspase-10 to form the death-inducing signaling complex (DISC) (Wilson, Nicholas S et al. Nature immunology vol. 10,4 (2009): 348-55.). DISC is activated by specific post-translational modifications of death receptors (DR), such as palmitoylation and O-linked glycosylation (Muppidi, Jagan R, and Richard M Siegel. Nature immunology vol. 5,2 (2004): 182- 9.; Wagner, Klaus W et al. Nature medicine vol. 13,9 (2007): 1070-7). DISC mediates the autocatalytic processing and activation of apoptotic protease-8 and apoptotic protease-10, which effect the proteolysis of apoptotic proteases through apoptotic protease-3, apoptotic protease-6, and apoptotic protease-7 Amplify the death signal. In type I cells, such as thymocytes, the action of cysteine proteases is sufficient to induce apoptosis. In contrast, in type II cells such as B cells, apoptosis requires caspase-8-mediated cleavage of the BH3-interacting domain death agonist (Bid), a BH3-only protein that can increase the permeability of the outer mitochondrial membrane and the release of cytochrome c. After cytochrome c is released from mitochondria, it can serve as a cofactor to participate in the assembly of a cytosolic apoptotic protease activation complex called the apoptosome, which can amplify the activation of the apoptotic protease cascade (Wagner, Klaus W et al. Nature medicine vol. 13,9 (2007): 1070-7.).

Cell death is not the only cellular response caused by Fas activation. Fas can also induce NF-κB signaling. Acting downstream of cellular caspase-8-like inhibitory protein (cFLIP) and TRAF2 in the Fas signaling pathway, it can induce T cell proliferation through NF-κB activation (Kataoka, Takao, and Jürg Tschopp. Molecular and cellular biology vol. 24, 7 (2004): 2627-36.). The N-terminal cleavage products of cFLIP, p43 FLIP and p22 FLIP, induce NF-κB activation by binding to the IKK complex (Golks, Alexander et al. The Journal of experimental medicine vol. 203,5 (2006): 1295-305.; Krammer , Peter H et al. Nature reviews. Immunology vol. 7,7 (2007): 532-42.). Furthermore, overexpression of cFLIP inhibits Fas-induced apoptosis of activated T cells (Van Parijs, L et al. "Autoimmunity as a consequence of retrovirus-mediated expression of C-FLIP in lymphocytes." Immunity vol. 11,6 (1999 ): 763-70.; Kirchhoff, S et al. Journal of immunology (Baltimore, Md.: 1950) vol. 165,11 (2000): 6293-300.). In addition, Fas signaling regulates peripheral T cell homeostasis by modulating the balance between proliferation and cell death, for example, in naive and memory T cell subsets (Jaleco, Sara et al. Journal of immunology (Baltimore, Md. . : 1950) vol. 171,1 (2003): 61-8.). Therefore, peripheral T cell homeostasis may be maintained by the dual effects of FasL/Fas signaling.

The Fas-FasL signaling pathway is related to the occurrence and development of various diseases, including autoimmune diseases, transplant rejection, spinal cord injury, sepsis, etc. Therefore, it is crucial to develop inhibitors targeting FasL targets.

At present, there have been reports on FasL inhibitors. For example, Chinese patent CN1283662C discloses antagonistic anti-hFAS ligand antibodies and their applications; Chinese patent CN108290950B discloses anti-FasL antibody 119-4A (used as a control antibody in the Examples of the present invention). and its application; Chinese patent CN104662039B discloses Fas-Fc fusion protein APG101 (used as a control in the Examples of the present invention) and its application. There is still a need for anti-FasL antibodies with high affinity and high biological activity in existing therapeutic areas.

The disclosure content of any publications, patents, patent applications, and published patent applications mentioned in this specification is fully incorporated by reference into this specification.

In some embodiments, an isolated anti-FasL antibody is provided, which includes: (i) _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 99. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 127; (ii) _VH , which comprises an amino group such as V _H comprising the HC-CDR1, HC-CDR2 and HC-CDR3 of the acid sequence SEQ ID NO: 100; and V _L comprising the LC of the V _L shown as the amino acid sequence SEQ ID NO: 128 -CDR1, LC-CDR2 and LC-CDR3; (iii) _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 101; and V _L , which includes LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL as shown in the amino acid sequence SEQ ID NO: 129; (iv) _VH , which includes the amino acid sequence SEQ ID NO: _VH shown in 102 includes HC-CDR1, HC-CDR2 and HC-CDR3; and _VL includes LC-CDR1, LC-CDR2 included in _VL shown in amino acid sequence SEQ ID NO: 130 and LC-CDR3; (v) _VH , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 103; and _VL , which comprises amines such as V _L shown in the amino acid sequence SEQ ID NO: 131 includes LC-CDR1, LC-CDR2 and LC-CDR3; (vi) V _H includes V _H shown in the amino acid sequence SEQ ID NO: 104 HC-CDR1, HC-CDR2 and HC-CDR3 comprised; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 132; ( vii) _VH , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 105; and _VL , which comprises the amino acid sequence SEQ ID NO : LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL shown in 133; (viii) _VH , including HC-CDR1 included in _VH shown in amino acid sequence SEQ ID NO: 106, HC-CDR2 and HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 134; (ix) _VH , which Comprising V _H comprising HC-CDR1, HC-CDR2 and HC-CDR3 as shown in the amino acid sequence SEQ ID NO: 107; and V _L comprising V as shown in the amino acid sequence SEQ ID NO: 135 _L contains LC-CDR1, LC-CDR2 and LC-CDR3; (x) _VH , which contains _VH containing HC-CDR1, HC-CDR2 and HC- as shown in the amino acid sequence SEQ ID NO: 108 CDR3; and _VL , which includes LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 136; (xi) _VH , which includes the amino acid sequence HC-CDR1, HC-CDR2 and HC-CDR3 included in V _H shown in SEQ ID NO: 109; and V _L including LC-CDR1 included in V _L shown in amino acid sequence SEQ ID NO: 137 , LC-CDR2 and LC-CDR3; (xii) V _H comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by V _H as shown in the amino acid sequence SEQ ID NO: 110; and V _L , It includes LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL as shown in the amino acid sequence SEQ ID NO: 138; (xiii) _VH , which includes the LC-CDR1, LC-CDR2 and LC-CDR3 as shown in the amino acid sequence SEQ ID NO: 111 The V _H shown includes HC-CDR1, HC-CDR2 and HC-CDR3; and V _L includes the LC-CDR1, LC-CDR2 and LC included in the V _L shown in the amino acid sequence SEQ ID NO: 139 -CDR3; (xiv) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 112; and _VL , which includes the amino acid V _L shown in sequence SEQ ID NO: 140 includes LC-CDR1, LC-CDR2 and LC-CDR3; (xv) V _H including V _H shown in amino acid sequence SEQ ID NO: 113 included HC-CDR1, HC-CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 141; (xvi) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 114; and _VL , which includes the amino acid sequence SEQ ID NO: 142 The V _L shown includes LC-CDR1, LC- _CDR2 and LC-CDR3; (xvii) V _H includes the HC-CDR1, HC- CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 143; (xviii) V _H comprising as The V _H containing the amino acid sequence SEQ ID NO: 116 includes HC-CDR1, HC-CDR2 and HC-CDR3; and V _L contains the V _L containing the amino acid sequence SEQ ID NO: 144. LC-CDR1, LC-CDR2 and LC-CDR3; (xix) _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 117; And _VL , which includes LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL as shown in the amino acid sequence SEQ ID NO: 145; (xx) _VH , which includes the amino acid sequence SEQ ID The V _H shown in NO: 118 includes HC-CDR1, HC-CDR2 and HC-CDR3; and V _L includes the LC-CDR1, LC included in the V _L shown in the amino acid sequence SEQ ID NO: 146 -CDR2 and LC-CDR3; (xxi) _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 119; and _VL comprising V _L as shown in the amino acid sequence SEQ ID NO: 147 includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxii) V _H includes as shown in the amino acid sequence SEQ ID NO: 120 _VH includes HC-CDR1, HC-CDR2 and HC-CDR3; and _VL includes _VL including LC-CDR1, LC-CDR2 and LC-CDR3 as shown in the amino acid sequence SEQ ID NO: 148 ; (xxiii) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 121; and _VL , which includes the amino acid sequence SEQ LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL shown in ID NO: 149; (xxiv) _VH , including _HC- included in VH shown in amino acid sequence SEQ ID NO: 122 CDR1, HC-CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 150; (xxv) V _H , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in V _H as shown in the amino acid sequence SEQ ID NO: 123; and V _L , which includes the amino acid sequence SEQ ID NO: 151 _VL includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxvi) _VH includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 124 HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 152; (xxvii) _VH , which comprises an amine group as shown V _H comprising the HC-CDR1, HC-CDR2 and HC-CDR3 of the acid sequence SEQ ID NO: 125; and V _L comprising the LC of the V _L shown as the amino acid sequence SEQ ID NO: 153 -CDR1, LC-CDR2 and LC-CDR3; or (xxviii) _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 126; and _VL , which includes LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL as shown in the amino acid sequence SEQ ID NO: 154.

In some embodiments, an isolated anti-FasL antibody is provided, which includes: (i) _VH , the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes Amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51. LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 77; (ii) V _H , the aforementioned V _H includes: HC-CDR1, It includes the amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 19, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and _VL , as described above _VL includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 51, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO : 78; (iii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3 , which includes the amino acid sequence SEQ ID NO: 32; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 79; (iv) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, HC- CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 33; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 80; (v) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 34; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 68. Sequence SEQ ID NO: 81; (vi) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 4, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, And HC-CDR3, which includes the amino acid sequence SEQ ID NO: 35; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 53, LC-CDR2, which includes the amino group Acid sequence SEQ ID NO: 69, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 82; (vii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 5. HC-CDR2, which includes the amino acid sequence SEQ ID NO: 21, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 36; and V _L , the aforementioned V _L includes: LC-CDR1, which includes Amino acid sequence SEQ ID NO: 54, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 70, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 83; (viii) V _H , as described above V _H includes: HC-CDR1, which contains the amino acid sequence SEQ ID NO: 6, HC-CDR2, which contains the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which contains the amino acid sequence SEQ ID NO : 37; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which Containing the amino acid sequence SEQ ID NO: 84; (ix) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 23, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, It includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (x) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and _VL , the aforementioned _VL includes: LC- CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (xi) _VH , the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 25. Sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC -CDR3, which contains the amino acid sequence SEQ ID NO: 85; (xii) V _H , the aforementioned V _H contains: HC-CDR1, which contains the amino acid sequence SEQ ID NO: 7, HC-CDR2, which contains the amino group Acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 72, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (xiii) V _H , the aforementioned V _H includes: HC-CDR1, which includes Amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L Comprising: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85. ; (xiv) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which Comprising the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L comprises: LC-CDR1, which comprises the amino acid sequence SEQ ID NO: 56, LC-CDR2, which comprises the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (xv) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, HC-CDR2, It includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 86; (xvi) V _H , the aforementioned V _H includes: HC- CDR1, which includes the amino acid sequence SEQ ID NO: 9, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 26, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 39; and V _L , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 57, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 87; (xvii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 27, and HC -CDR3, which includes the amino acid sequence SEQ ID NO: 40; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 58, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 88; (xviii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 10, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 41; and V _L , the aforementioned V _L includes: LC-CDR1, which includes an amino group Acid sequence SEQ ID NO: 59, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 89; (xix) V _H , the aforementioned V _H Comprising: HC-CDR1, which contains the amino acid sequence SEQ ID NO: 6, HC-CDR2, which contains the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which contains the amino acid sequence SEQ ID NO: 37 ; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amine The amino acid sequence is SEQ ID NO: 90; (xx) V _H. The aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 11, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 42; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes Amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 91; (xxi) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 43; and V _L , the aforementioned V _L includes: LC-CDR1, It includes the amino acid sequence SEQ ID NO: 61, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 92; (xxii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 44; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 62, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3 , which includes the amino acid sequence SEQ ID NO: 93; (xxiii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 13, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 30, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 45; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 63, LC- CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 94; (xxiv) V _H , the aforementioned V _H includes: HC-CDR1, which includes an amino group Acid sequence SEQ ID NO: 14, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 46; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 95; ( xxv) _VH , the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 15, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amine The amino acid sequence SEQ ID NO: 47; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 64, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, And LC-CDR3, which includes the amino acid sequence SEQ ID NO: 96; (xxvi) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 16, HC-CDR2, which includes The amino acid sequence SEQ ID NO: 31, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 48; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 65. LC-CDR2, which includes the amino acid sequence SEQ ID NO: 76, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 97; (xxvii) V _H , the aforementioned V _H includes: HC-CDR1, It includes the amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 49; and _VL , as described above _VL includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 66, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO : 98; or (xxviii) V _H , the aforementioned V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC- CDR3, which includes the amino acid sequence SEQ ID NO: 50; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 91.

In some embodiments, any of the isolated anti-FasL antibodies as described above includes: _VH , which includes the amino acid sequence shown in SEQ ID NO: 99 or a variant thereof, and the aforementioned variant is the same as SEQ ID NO: The amino acid sequence shown in 99 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 127 or a variant thereof, the aforementioned variant is the same as that shown in SEQ ID NO: 127 The amino acid sequence shown has at least about 80% sequence identity; (ii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 100 or a variant thereof, the aforementioned variant is the same as that shown in SEQ ID NO: 100 The amino acid sequence shown has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 128 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 128 The amino acid sequence has at least about 80% sequence identity; (iii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 101 or a variant thereof, the aforementioned variant is the same as that shown in SEQ ID NO: 101 The amino acid sequence has at least about 80% sequence identity; and V _L includes the amino acid sequence shown in SEQ ID NO: 129 or a variant thereof, the aforementioned variant having an amino group shown in SEQ ID NO: 129 The acid sequence has at least about 80% sequence identity; (iv) _VH , which includes the amino acid sequence shown in SEQ ID NO: 102 or a variant thereof, the aforementioned variant is the same as the amino group shown in SEQ ID NO: 102 The acid sequence has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 130 or a variant thereof, the aforementioned variant and the amino acid sequence shown in SEQ ID NO: 130 Having at least about 80% sequence identity; (v) _VH , which includes the amino acid sequence shown in SEQ ID NO: 103 or a variant thereof, the aforementioned variant and the amino acid sequence shown in SEQ ID NO: 103 Have at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 131 or a variant thereof, the aforementioned variant has at least 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 131 About 80% sequence identity; (vi) _VH , which includes the amino acid sequence shown in SEQ ID NO: 104 or a variant thereof, which has at least About 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 132 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 132 % sequence identity; (vii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 105 or a variant thereof, which has at least about 80% affinity with the amino acid sequence shown in SEQ ID NO: 105 % sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 133 or a variant thereof, the aforementioned variant having at least about 80% sequence with the amino acid sequence shown in SEQ ID NO: 133 Identity; (viii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 106 or a variant thereof, the aforementioned variant having at least about 80% sequence with the amino acid sequence shown in SEQ ID NO: 106 Identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 134 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 134 ; (ix) _VH , which includes the amino acid sequence shown in SEQ ID NO: 107 or a variant thereof, the aforementioned variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 107 ; And _VL , which includes the amino acid sequence shown in SEQ ID NO: 135 or a variant thereof, the aforementioned variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 135; ( x) _VH , which includes the amino acid sequence shown in SEQ ID NO: 108 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 108; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 136 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 136; (xi) _VH , which includes the amino acid sequence shown in SEQ ID NO: 109 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 109; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 137 or a variant thereof, the aforementioned variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 137; (xii) V _H , which includes the amino acid sequence shown in SEQ ID NO: 110 or a variant thereof, the aforementioned variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 110; and _VL , which Comprising the amino acid sequence shown in SEQ ID NO: 138 or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 138; (xiii) V _H , which Comprising the amino acid sequence shown in SEQ ID NO: 111 or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 111; and _VL , which includes SEQ The amino acid sequence shown in ID NO: 139 or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 139; (xiv) V _H , which includes SEQ The amino acid sequence shown in ID NO: 112 or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 112; and _VL , which includes SEQ ID NO : The amino acid sequence shown in 140 or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 140; (xv) V _H , which includes SEQ ID NO : The amino acid sequence shown in SEQ ID NO: 113 or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 113; and _VL , which includes SEQ ID NO: 141 The amino acid sequence shown or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 141; (xvi) V _H , which includes SEQ ID NO: 114 The amino acid sequence shown or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 114; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 142 The amino acid sequence or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 142; (xvii) V _H , which includes SEQ ID NO: 115 The amino acid sequence or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 115; and _VL , which contains the amine shown in SEQ ID NO: 143 The amino acid sequence or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 143; (xviii) _VH , which contains the amine shown in SEQ ID NO: 116 The amino acid sequence or a variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 116; and _VL , which includes the amino acid shown in SEQ ID NO: 144 Sequence or variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 144; (xix) V _H , which includes the amino acid sequence shown in SEQ ID NO: 117 Sequence or variant thereof, the aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 117; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 145 or Variants thereof, the aforementioned variants have at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 145; (xx) _VH , which includes the amino acid sequence shown in SEQ ID NO: 118 or Variants thereof, the aforementioned variants have at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 118; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 146 or a variant thereof The aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 146; (xxi) _VH , which includes the amino acid sequence shown in SEQ ID NO: 119 or a variant thereof The aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 119; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 147 or a variant thereof, The aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 147; (xxii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 120 or a variant thereof, The aforementioned variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 120; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 148 or a variant thereof, the aforementioned variant The body has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 148; (xxiii) V _H , which includes the amino acid sequence shown in SEQ ID NO: 121 or a variant thereof, the aforementioned variant The body has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 121; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 149 or a variant thereof, the aforementioned variant is the same as The amino acid sequence shown in SEQ ID NO: 149 has at least about 80% sequence identity; (xxiv) _VH , which includes the amino acid sequence shown in SEQ ID NO: 122 or a variant thereof, the aforementioned variant is the same as The amino acid sequence shown in SEQ ID NO: 122 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 150 or a variant thereof, the aforementioned variant being identical to SEQ ID The amino acid sequence shown in NO: 150 has at least about 80% sequence identity; (xxv) _VH , which includes the amino acid sequence shown in SEQ ID NO: 123 or a variant thereof, the aforementioned variant is the same as SEQ ID The amino acid sequence shown in NO: 123 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 151 or a variant thereof, the aforementioned variant being identical to SEQ ID NO: The amino acid sequence shown in 151 has at least about 80% sequence identity; (xxvi) _VH , which includes the amino acid sequence shown in SEQ ID NO: 124 or a variant thereof, the aforementioned variant is the same as SEQ ID NO: The amino acid sequence shown in SEQ ID NO: 124 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 152 or a variant thereof, the aforementioned variant is the same as that shown in SEQ ID NO: 152 The amino acid sequence shown has at least about 80% sequence identity; (xxvii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 125 or a variant thereof, the aforementioned variant is the same as that shown in SEQ ID NO: 125 The amino acid sequence shown has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 153 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 153 The amino acid sequence has at least about 80% sequence identity; or (xxviii) _VH , which contains the amino acid sequence shown in SEQ ID NO: 126 or a variant thereof, the aforementioned variant is the same as that shown in SEQ ID NO: 126 The amino acid sequence has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 154 or a variant thereof, the aforementioned variant is the same as the amine shown in SEQ ID NO: 154 The amino acid sequences have at least about 80% sequence identity.

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

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

In some embodiments, an isolated nucleic acid molecule encoding any of the anti-FasL antibodies as described above is provided. In some embodiments, a vector is provided, and the aforementioned vector contains any nucleic acid molecule as described above. In some embodiments, a host cell is provided, and the host cell contains any one of the above-mentioned anti-FasL antibodies, any one of the above-mentioned nucleic acid molecules, or any one of the above-mentioned vectors. In some embodiments, a method for preparing anti-FasL antibodies is provided, which includes: a) culturing any of the above host cells under conditions that can effectively express anti-FasL antibodies; and b) obtaining expressed anti-FasL antibodies from the host cells .

In some embodiments, a method of treating a disease or disorder in a desired individual is provided, comprising administering to the individual an effective amount of any of the anti-FasL antibodies described above. In some embodiments, the use of any of the anti-FasL antibodies described above in the preparation of a pharmaceutical composition for treating a disease or condition in a desired individual is provided. In some embodiments, the use of any anti-FasL antibody or a pharmaceutical composition comprising an anti-FasL antibody as described above in the preparation of a medicament for treating a disease or condition is provided. In some embodiments, the aforementioned diseases or disorders are related to the FasL-Fas signaling pathway, including inflammatory diseases, cancer, or autoimmune diseases or disorders. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is FasL-positive cancer.

Pharmaceutical compositions, kits and manufactured products containing any of the anti-FasL antibodies mentioned above are also provided.

In one aspect, the invention provides anti-FasL antibody molecules. Through a combination of natural scFv phage library screening, appropriately designed biochemical and biological experiments, and antibody humanization, highly efficient antibody molecules capable of binding human FasL and inhibiting the interaction of human FasL with its receptor have been identified. The results shown in this specification indicate that the antibody of the present invention has better biological activity than the known anti-FasL antibody.

The anti-FasL antibodies provided by the present invention include, for example, full-length anti-FasL antibodies, anti-FasL single chain antibodies (scFvs), anti-FasL Fc fusion proteins, multispecific (such as bispecific) anti-FasL antibodies, and anti-FasL immunoconjugates. things and the like.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 99. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 127.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 100. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 128.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 101. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 129.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 102. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 130.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 103. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 131.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 104. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 132.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 105. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 133.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 106. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 134.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 107. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 135.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 108. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 136.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 109. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 137.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 110. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 138.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 111. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 139.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 112. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 140.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 113. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 141.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 114. HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 142.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 115. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 143.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 116. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 144.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 117. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 145.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 118. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 146.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 119. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 147.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 120. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 148.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 121. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 149.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 122. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 150.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 123. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 151.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 124. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 152.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 125. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 153.

In another aspect, the present invention provides an anti-FasL antibody. The aforementioned anti-FasL antibody includes: _VH , which includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 126. HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 154.

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

definition

As used in this specification, "treatment" or "treating" refers to a method of obtaining beneficial or desired results, including clinical results. In view of the purpose of the present invention, the aforementioned beneficial or desired clinical results include, but are not limited to, one or more of the following: alleviating one or more symptoms caused by the disease, reducing the severity of the disease, stabilizing the disease (for example, preventing or delaying the progression of the disease) , prevent or delay the spread of the disease (e.g., metastasis), prevent or delay the recurrence of the disease, delay or slow the progression of the disease, improve the disease state, alleviate the disease (partially or completely), reduce the dose of one or more other drugs required to treat the disease , delay disease progression, improve or improve quality of life, increase weight, and/or prolong survival. At the same time, "treatment" also includes the reduction of the pathological consequences of the disease (for example, in the case of cancer, tumor volume). The methods of the present invention contemplate any one or more of these aspects of treatment.

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

As used herein, the term "antigen-binding fragment" includes antibody fragments, e.g., diabodies, Fab, Fab', F(ab') ₂ , Fv fragments, disulfide-stabilized Fv fragments (dsFv) , (dsFv) _2. Bispecific dsFv (dsFv-dsFv'), disulfide bond-stabilized diabody (ds diabody), single-chain Fv (scFv), scFv dimer (bivalent diabody) , multispecific antibodies, single domain antibodies, nanobodies, domain antibodies, bivalent domain antibodies composed of antibody fragments containing one or more CDRs, or any other antibody capable of binding to an antigen but not containing a complete antibody structure Antibody fragments. Antigen-binding fragments are capable of binding to the same antigen as the parent antibody or parent antibody fragment (such as the parent scFv). Antigen-binding fragments also include fusion proteins containing the above-described antibody fragments. In some embodiments, the antigen-binding fragment may comprise one or more CDRs from a specific human antibody grafted to framework regions from one or more different human antibodies.

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

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

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

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

As used herein, the term "isolated nucleic acid" refers to nucleic acids of genomic, cDNA or synthetic origin, or combinations thereof. According to its source, the aforementioned "isolated nucleic acid" refers to (1) not related to all or part of the polynucleotides in the "isolated nucleic acid" found in nature, (2) not associated with polynucleotides in the natural state. The acid is operably linked, or (3) does not occur in nature as part of a longer sequence.

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

Table 1: CDR definition Kabat ¹ Chothia ² MacCallum ³ IMGT ⁴ AHo ⁵ V _H CDR1 31-35 26-32 30-35 27-38 25-40 V _H CDR2 50-65 53-55 47-58 56-65 58-77 V _H CDR3 95-102 96-101 93-101 105-117 109-137 V _L CDR1 24-34 26-32 30-36 27-38 25-40 V _L CDR2 50-56 50-52 46-55 56-65 58-77 V _L CDR3 89-97 91-96 89-96 105-117 109-137 ¹ The numbering of amino acid residues refers to the nomenclature method in Kabat et al. above. ² The numbering of amino acid residues refers to the nomenclature method in Chothia et al. above. ³ The numbering of amino acid residues refers to the nomenclature in MacCallum et al. Method ^4: The numbering of amino acid residues refers to the nomenclature method in Lefranc et al. above ^{. 5:} The numbering of amino acid residues refers to the nomenclature method in Honegger and Plückthun above.

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

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

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

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

"Humanized" forms of non-human (eg, rodent) antibodies are chimeric antibodies that contain minimal sequence from the non-human antibody. In most cases, humanized antibodies are human immunoglobulins (recipient antibodies) in which the hypervariable region (HVR) residues of the receptor antibody are modified from a non-human species such as mouse, rat, rabbit or Replacement of hypervariable region residues from a non-human mammalian species with desirable antibody specificity, affinity, and performance (donor antibody). In some cases, residues in the human immunoglobulin framework region are replaced with corresponding non-human residues. Additionally, humanized antibodies may contain residues that are not present in either the recipient antibody or the donor antibody. These modifications can further improve the performance of the antibody. Typically, a humanized antibody will contain substantially all, at least one, and usually two variable domains in which all or substantially all of the hypervariable loops correspond to hypervariable loops of a non-human immunoglobulin, and all or Essentially all framework regions are human immunoglobulin sequences. The human antibody optionally further comprises at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For specific 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).

The "amino acid sequence identity percentage (%)" or "homology" of the polypeptide and antibody sequences identified in this specification is defined: Sequence comparison is performed when conservative substitutions are considered to be part of the sequence identity, and the candidate The percentage of identical amino acid residues between the sequence and the polypeptide sequence to be compared. The percentage of amino acid sequence identity can be determined by a variety of alignment methods within the technical scope of the present invention, for example, using publicly available software such as BLAST, BLAST-2, ALIGN, Megalign (DNASTAR), or MUSCLE software. Computer software. One of ordinary skill in the art can determine appropriate parameters for measuring alignment, including any algorithm required to maximize alignment over the full length of the sequences being compared. However, for the purposes of this specification, percent amino acid sequence identity values are calculated using the sequence alignment computer program MUSCLE (Edgar, R.C., Nucleic Acids Research 32(5):1792-1797, 2004; Edgar, R.C., BMC Bioinformatics 5 (1):113, 2004).

The term "Fc receptor" or "FcR" is used to describe a receptor that binds to the Fc region of an antibody. In some embodiments, the FcR of the present invention is an FcR that binds an IgG antibody (a gamma receptor), including receptors of the FcγRI, FcγRII, and FcγRIII subclasses, including allelic variants and can Change splicing form. FcγRII receptors include FcγRIIA (“activating receptor”) and FcγRIIB (“inhibitory receptor”), which have similar amino acid sequences and differ mainly in the cytoplasmic domain. The cytoplasmic domain of the activating receptor FcγRIIA contains the immunoreceptor tyrosine activation motif (ITAM). The cytoplasmic domain of the inhibitory receptor FcγRIIB contains the immunoreceptor tyrosine inhibitory motif (ITIM) (see M. in Daëron, Annu. Rev. Immunol. 15:203-234 (1997)). The foregoing term also includes allotypes, such as FcγRIIIA allotypes: FcγRIIIA-Phe158, FcγRIIIA-Val158, FcγRIIA-R131 and/or FcγRIIA-H131. In Ravetch and Kinet, Annu. Rev. Immunol 9:457-92 (1991) and Capel et al., Immunomethods 4:25-34 (1994); and de Haas et al., J. Lab. Clin. Med. 126 FcRs are described in :330-41 (1995). The term FcR in the present invention encompasses other types of FcRs, including FcRs to be identified in the future. The term FcR also includes the neonatal receptor FcRn, which is responsible for the transfer of maternal IgGs to the newborn (Guyer et al., J. Immunol. 117:587 (1976) and Kim et al., J. Immunol. 24:249 (1994) )).

The term "FcRn" refers to the neonatal Fc receptor (FcRn). FcRn is structurally similar to the major histocompatibility complex (MHC) and consists of an α chain non-covalently bound to β2 microglobulin. The diverse functions of the neonatal Fc receptor FcRn are reviewed in Ghetie and Ward (2000) Annu. Rev. Immunol. 18, 739-766. FcRn plays an important role in the passive transport of immunoglobulin IgGs from mother to newborn and in regulating serum IgG levels. As a rescue receptor, FcRn can bind and transport endocytosed IgG in an intact form within and between cells and protect it from the default degradation pathway.

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

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

The "CH2 domain" of the human IgG Fc region usually extends from amino acid 231 to amino acid 340. The unique feature of the CH2 domain is that it does not pair closely with another region, but inserts two N-terminally connected branched sugar chains between the two CH2 domains of the intact natural IgG molecule. It is speculated that sugars may serve as a surrogate for domain-to-domain pairing, helping to keep the CH2 domain stable. Burton, Molec. Immunol. 22:161-206 (1985).

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

"Functional Fc fragments" have the "effector function" possessed by the native Fc region sequence. Exemplary "effector functions" include C1q binding; complement-dependent cytotoxicity (CDC); Fc receptor binding; antibody-dependent cell-mediated cytotoxicity (ADCC); phagocytosis; downregulation of cell surface receptors ( Such as B cell receptor; BCR), etc. Such effector functions typically require the Fc region to bind to a binding domain (such as an antibody variable region) and can be assessed using a variety of experimental methods well known in the art.

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

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

Polypeptides containing Fc region variants exhibit "enhanced ADCC activity" or are able to mediate ADCC effects more effectively in the presence of human effector cells than polypeptides containing wild-type IgG Fc polypeptides or parent polypeptides containing Fc region variants. When the antibody polypeptide is substantially the same as the wild-type IgG Fc polypeptide (or parent polypeptide) in the experiment, it can more effectively mediate ADCC both in vitro and in vivo. Such variants are generally identified using any in vitro ADCC assay known in the art, such as assays or methods for identifying ADCC activity, such as in animal models. In some embodiments, such variants mediate ADCC 5 to 100-fold, for example, 25- to 50-fold more efficiently than wild-type Fc (or the parent polypeptide).

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

Unless otherwise stated, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerates of each other and encode the same amino acid sequence. Nucleotide sequences encoding proteins or RNA may also contain introns. For example, nucleotide sequences encoding proteins may contain introns in some forms.

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

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

The "effective amount" of the anti-FasL antibody or composition disclosed in this specification refers to the amount sufficient to achieve a specific purpose. The "effective amount" can be determined empirically and by methods known to be relevant to the aforementioned purposes.

The term "therapeutically effective dose" refers to the amount of anti-FasL antibody or composition disclosed in this specification that can effectively treat an individual's disease or symptoms, that is, it is sufficient to reduce or improve the severity and/or persistence of the disease or one or more symptoms thereof. Amount of time; to prevent the development of a disease, to cause resolution of a condition, to prevent the recurrence, development, onset, or progression of one or more symptoms associated with a disease, to detect a disease, or to enhance/improve the prevention of another therapy (e.g., a prophylactic or therapeutic agent) or the amount of therapeutic effect. For example, in the context of cancer, a therapeutically effective amount of an anti-FasL antibody or composition thereof is one that reduces the number of cancer cells; reduces the size or weight of the tumor; inhibits (i.e., slows or ideally stops to a certain extent) the impact of tumor cells on surrounding cells. Invasion of organs; inhibition (i.e., slowing down or ideally stopping to a certain extent) tumor metastasis; inhibiting tumor growth to a certain extent, and/or alleviating one or more symptoms related to cancer to a certain extent. The anti-FasL antibody or its composition disclosed in this specification can prevent or inhibit the binding of FasL to its receptor Fas to a certain extent. In addition to the apoptosis signaling pathway, Fas-mediated non-apoptotic signals ( Such as NF-kB, MAPK, or PI3K), this non-apoptotic signal promotes inflammation, promotes carcinogenesis, and modulates immunological parameters (e.g., tumor-infiltrating T cell populations). All of these activities may be inhibited by the antibodies described herein.

As used in this specification, "pharmaceutically acceptable" or "pharmacologically compatible" refers to materials that have no biological activity or other undesirable properties, such as materials that can be incorporated into a pharmaceutical composition for administration to a patient, and Does not cause significant adverse biological reactions or interact in a deleterious manner with any other components contained in the composition. A pharmaceutically acceptable carrier or excipient ideally meets required standards for toxicological or manufacturing testing and/or is included in the Inactive Ingredient Guidelines prepared by the U.S. Food and Drug Administration.

The embodiments of the invention described in this specification should be understood to include embodiments "consisting of" and/or "consisting essentially of".

The term “approximately” mentioned in this specification refers to a numerical value or parameter, including (and describing) variations on the value or parameter itself. For example, the description of "about X" includes the description of "X".

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

Unless the context clearly dictates otherwise, when used in this specification and the claimed claims, the singular forms "a," "an," and "the" include plural referents.

anti-FasL antibody

In one aspect, the invention provides anti-FasL antibodies that specifically bind human FasL. The aforementioned anti-FasL antibodies include, but are not limited to, humanized antibodies, chimeric antibodies, mouse antibodies, human antibodies, and antibody molecules containing heavy chain and/or light chain CDRs described in this specification. In one aspect, the invention provides isolated antibodies that bind FasL. Anti-FasL antibodies contemplated include, for example, full-length anti-FasL antibodies (e.g., full-length IgG1 or IgG4), anti-FasL single chain antibodies, anti-FasL Fc fusion proteins, multispecific (e.g., bispecific) anti-FasL antibodies, anti-FasL immunoconjugates Connected objects, and the like. In some embodiments, the anti-FasL antibody is a full-length antibody (such as full-length IgG1 or IgG4) or an antigen-binding fragment thereof, which specifically binds to FasL. In some embodiments, anti-FasL antibody systems Fab, Fab', F(ab)' ₂ , Fab'-SH, single chain Fv (scFv), Fv fragment, dAb, Fd, nanobody (nanobody), double chain Antibody (diabody) or linear antibody. In some embodiments, the antibody that specifically binds FasL refers to an antibody whose affinity for binding to FasL is at least 10 times greater than its binding affinity for non-targets (including, for example, 10, 10 ² , 10 ³ , 10 ⁴ , 10 ⁵ , 10 ⁶ , or 10 ⁷ times). In some embodiments, non-target refers to an antigen other than FasL. Binding affinity can be determined by methods known in the art of the present invention, such as ELISA, fluorescence-activated cell sorting (FACS) analysis or radioimmunoprecipitation analysis (RIA). The Kd value can be measured by methods known in the technical field of the present invention, such as surface plasmon resonance (SPR) technology or biolayer interference (BLI) technology.

Although this specification broadly discusses anti-FasL antibodies comprising human sequences (eg, human heavy and light chain variable domains comprising human CDR sequences), non-human anti-FasL antibodies are also contemplated. In some embodiments, the non-human anti-FasL antibody includes the human CDR sequence and the non-human framework region sequence of the anti-FasL antibody described in this specification. In some embodiments, the non-human framework region sequence includes any sequence for use as described herein. One or more human CDR sequences described in the specification generate sequences of heavy chain and/or light chain variable domains, including, for example, mammals, such as mice, rats, rabbits, pigs, cattle (e.g., cattle, bulls, buffaloes ), deer, sheep, goats, chickens, cats, dogs, ferrets, primates (e.g., small apes, macaques), etc. In some embodiments, non-human anti-FasL antibodies comprise anti-FasL antibodies produced by grafting one or more human CDR sequences described herein into non-human framework regions (eg, mouse or chicken framework region sequences).

The complete amino acid sequence of an exemplary human FasL includes or consists of the amino acid sequence shown in SEQ ID NO: 159. An exemplary human FasL extracellular region amino acid sequence includes or consists of the amino acid sequence shown in SEQ ID NO: 160.

In some embodiments, the anti-FasL antibodies described herein specifically recognize an epitope in human FasL. In some embodiments, the aforementioned anti-FasL antibodies cross-react with FasL of species other than humans. In some embodiments, the aforementioned anti-FasL antibodies are completely specific for the human FasL lineage and do not cross-react with other non-human species.

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

In some embodiments, the aforementioned anti-FasL antibody cross-reacts with at least one interspecies variant of the FasL protein. In some embodiments, for example, the FasL protein (or fragment thereof) is human FasL, and the interspecies variant of the FasL protein (or fragment thereof) is a variant in cynomolgus monkey. In some embodiments, the aforementioned anti-FasL antibodies do not cross-react with any interspecies variant of the FasL protein.

In some embodiments, as any anti-FasL antibody described in this specification, the aforementioned anti-FasL antibody includes an antibody heavy chain constant region and an antibody light chain constant region. In some embodiments, the aforementioned anti-FasL antibody comprises an IgG1 heavy chain constant region. In some embodiments, the aforementioned anti-FasL antibody comprises an IgG2 heavy chain constant region. In some embodiments, the aforementioned anti-FasL antibody comprises an IgG3 heavy chain constant region. In some embodiments, the aforementioned anti-FasL antibody comprises an IgG4 heavy chain constant region. In some embodiments, the aforementioned heavy chain constant region includes (comprises or consists essentially of) the amino acid sequence SEQ ID NO: 155. In some embodiments, the aforementioned heavy chain constant region includes (comprises or consists essentially of) the amino acid sequence SEQ ID NO: 156. In some embodiments, the aforementioned anti-FasL antibody comprises a kappa light chain constant region. In some embodiments, the aforementioned light chain constant region includes (comprises or consists essentially of) the amino acid sequence SEQ ID NO: 157. In some embodiments, the aforementioned anti-FasL antibody comprises a lambda light chain constant region. In some embodiments, the aforementioned light chain constant region includes (comprises or consists essentially of) the amino acid sequence SEQ ID NO: 158. In some embodiments, the aforementioned anti-FasL antibody includes an antibody heavy chain variable domain and an antibody light chain variable domain.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 32, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 51, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 67, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 77, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 67, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 77.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 99; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 127.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 99 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 99 of at least about 80% % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 127 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 127 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 99, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 127.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 2, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 19. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 32, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 51, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 78, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 2, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 19. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 68, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 78.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 100; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 128.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 100 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 100 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 128 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 128 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 100, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 128.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 32, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 51, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 67, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 79, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 67, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 79.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 101; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 129.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 101 or a variant thereof, and the aforementioned variant has at least about 80% relationship with the amino acid sequence SEQ ID NO: 101. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 129 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 129 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 101, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 129.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 33, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 52, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 80, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 33; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 68, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 80.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 102; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 130.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 102 or a variant thereof, and the aforementioned variant has at least about 80% relationship with the amino acid sequence SEQ ID NO: 102. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 130 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 130 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 102, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 130.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 34, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 52, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 81, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 34; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 68, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 81.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 103; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 131.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 103 or a variant thereof, and the aforementioned variant has at least about 80% difference with the amino acid sequence SEQ ID NO: 103. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 131 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 131 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 103, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 131.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 4, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 35, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 53, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 69, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 82, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 4, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 35; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 53, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 69, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 82.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 104; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 132.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 104 or a variant thereof, and the aforementioned variant has at least about 80% difference with the amino acid sequence SEQ ID NO: 104. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 132 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 132 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 104, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 132.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 5, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 21. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 36, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 54, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 70, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 83, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 5, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 21. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 36; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 54, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 70, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 83.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 105; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 133.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 105 or a variant thereof, and the aforementioned variant has at least about 80% difference with the amino acid sequence SEQ ID NO: 105. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 133 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 133 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 105, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 133.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 6, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 37, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 84, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 6, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 84.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 106; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 134.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 106 or a variant thereof, and the aforementioned variant has at least about 80% difference with the amino acid sequence SEQ ID NO: 106. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 134 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 134 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 106, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 134.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 23. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 23. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 85.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 107; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 135.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 107 or a variant thereof, and the aforementioned variant has at least about 80% difference with the amino acid sequence SEQ ID NO: 107. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 135 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 135 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 107, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 135.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 37, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 85.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 108; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 136.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 108 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 108 with at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 136 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 136 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 108, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 136.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 85.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 109; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 137.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 109 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 109 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 137 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 137 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 109, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 137.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 72, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 72, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 85.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 110; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 138.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 110 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 110 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 138 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 138 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 110, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 138.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 85.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 111; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 139.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 111 or a variant thereof, and the aforementioned variant has an amino acid sequence of at least about 80% with the amino acid sequence SEQ ID NO: 111. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 139 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 139 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 111, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 139.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 56, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 56, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 85.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 112; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 140.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 112 or a variant thereof, and the aforementioned variant has an amino acid sequence of at least about 80% with the amino acid sequence SEQ ID NO: 112. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 140 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 140 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 112, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 140.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 86, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 86.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 113; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 141.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 113 or a variant thereof, the aforementioned variant has an amino acid sequence of at least about 80% with the amino acid sequence SEQ ID NO: 113. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 141 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 141 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 113, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 141.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 9, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 26. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 39, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 57, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 73, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 87, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 9, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 26. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 39; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 57, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 73, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 87.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 114; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 142.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 114 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 114 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 142 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 142 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 114, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 142.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 2, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 27. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 40, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 58, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 73, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 88, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 2, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 27. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 40; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 58, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 73, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 88.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 115; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 143.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 115 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 115 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 143 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 143 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 115, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 143.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 10, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 41, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 59, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 89, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 10, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 41; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 59, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 68, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 89.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 116; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 144.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 116 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 116 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 144 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 144 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 116, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 144.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 6, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 37, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 90, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 6, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 90.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 117; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 145.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 117 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 117 of at least about 80% % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 145 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 145 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 117, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 145.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 11, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 42, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 60, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 74, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 91, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 11, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 42; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 74, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 91.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 118; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 146.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 118 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 118 with at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 146 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 146 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 118, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 146.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 43, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 61, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 75, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 92, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 43; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 61, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 75, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 92.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 119; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 147.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 119 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 119 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 147 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 147 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 119, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 147.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 44, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 62, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 75, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 93, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 44; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 62, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 75, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 93.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 120; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 148.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 120 or a variant thereof, and the aforementioned variant has at least about 80% relationship with the amino acid sequence SEQ ID NO: 120. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 148 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 148 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 120, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 148.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 13, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 30. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 45, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 63, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 73, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 94, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 13, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 30. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 45; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 63, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 73, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 94.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 121; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 149.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 121 or a variant thereof, and the aforementioned variant has an amino acid sequence of at least about 80% with the amino acid sequence SEQ ID NO: 121. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 149 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 149 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 121, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 149.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 14, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 46, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 51, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 95, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 14, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 46; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 68, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 95.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 122; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 150.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 122 or a variant thereof, and the aforementioned variant has an amino acid sequence of at least about 80% with the amino acid sequence SEQ ID NO: 122. % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 150 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 150 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 122, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 150.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 15, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 47, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 64, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 96, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 15, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 47; and _VL , the aforementioned _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 64, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 68, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 96.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 123; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 151.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 123 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 123 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 151 or Variants thereof, the aforementioned variants have at least about 80% (for example, at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 151 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 123, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 151.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 16, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 31. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 48, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 65, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 76, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 97, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 16, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 31. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 48; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 65, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 76, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 97.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 124; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 152.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 124 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 124 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 152 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 152 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 124, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 152.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 17, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 49, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 66, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 74, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 98, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 17, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 49; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 66, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 74, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 98.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 125; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 153.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 125 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 125 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 153 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 153 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 125, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 153.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 17, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28. , HC-CDR3, which contains the amino acid sequence SEQ ID NO: 50, or a variant of the aforementioned V _H , whose HC-CDRs contain up to about 5 amino acid substitutions; and V _L , where the aforementioned V _L includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 60, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 74, LC-CDR3, which contains the amino acid sequence SEQ ID NO: 91, or the aforementioned Variants of V _L containing up to about 5 amino acid substitutions in their LC-CDRs.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , and the aforementioned _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 17, and HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28. , and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 50; and V _L , the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amine The amino acid sequence is SEQ ID NO: 74, and LC-CDR3 includes the amino acid sequence SEQ ID NO: 91.

In some embodiments, the aforementioned anti-FasL antibody includes _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 126; and _VL , which Contains LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 154.

In some embodiments, the aforementioned anti-FasL antibody includes: _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 126 or a variant thereof, and the aforementioned variant has an amino acid sequence of SEQ ID NO: 126 of at least about 80 % (e.g., at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99%) sequence identity; and V _L , the aforementioned V _L comprising the amino acid sequence SEQ ID NO: 154 or Variants thereof, the aforementioned variants have at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence with the amino acid sequence SEQ ID NO: 154 Identity. In some embodiments, the aforementioned anti-FasL antibody includes _VH , the aforementioned _VH includes the amino acid sequence SEQ ID NO: 126, and _VL , the aforementioned _VL includes the amino acid sequence SEQ ID NO: 154.

In some embodiments, the above-mentioned amino acid substitutions are limited to the "exemplary substitutions" shown in Table 4 of this specification. In some embodiments, amino acid substitution is limited to the "ideal substitution" shown in Table 4 of this specification.

In some embodiments, functional epitopes can be resolved by combining alanine scanning. In this process, combinatorial alanine scanning technology can be used to identify amino acids in the FasL protein that are necessary for interaction with anti-FasL antibodies. In some embodiments, the epitope is conformational, and the crystal structure of an anti-FasL antibody bound to the FasL protein can be used to identify the epitope.

In some embodiments, the invention provides antibodies that compete with any of the anti-FasL antibodies described herein for binding to FasL. In some embodiments, an antibody capable of competitively binding to an epitope on FasL with any of the anti-FasL antibodies described herein is provided. In some embodiments, an anti-FasL antibody is provided that binds to the same epitope as an anti-FasL antibody molecule comprising V _H and V _L , wherein the aforementioned V _H comprises an amine group shown in any one of SEQ ID NOs: 99-126 The acid sequence, and the aforementioned _VL include the amino acid sequence shown in any one of SEQ ID NOs: 127-154. In some embodiments, an anti-FasL antibody is provided, which competitively binds to FasL with an anti-FasL antibody comprising V _H and V _L , wherein the aforementioned V _H comprises the amino acid shown in any one of SEQ ID NOs: 99-126 The sequence, and the aforementioned _VL include the amino acid sequence shown in any one of SEQ ID NOs: 127-154.

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

Exemplary anti-FasL antibody sequences are shown in Table 2 and Table 3, where CDR numbering is performed according to the Chothia definition. One of ordinary skill in the art will recognize that there are a variety of known algorithms (Chothia definitions) for predicting the positions of CDRs and defining antibody light and heavy chain variable regions. Antibodies that include the CDRs, _VH and/or _VL sequences of the antibodies described herein, but are based on prediction algorithms other than those exemplified in the table below are also within the scope of the invention.

Table 2 Exemplary anti-FasL antibody CDR sequences Antibody name HC-CDR1 HC-CDR2 HC-CDR3 FL-M04 GYTFTKY (SEQ ID NO: 1) TYQG (SEQ ID NO: 18) PDWDYAMD (SEQ ID NO: 32) FL-M06 GYTFTDY (SEQ ID NO: 2) TYNG (SEQ ID NO: 19) PDWDYAMD (SEQ ID NO: 32) FL-M07 GYTFTKY (SEQ ID NO: 1) TYQG (SEQ ID NO: 18) PDWDYAMD (SEQ ID NO: 32) FL-M09 GYTFTSY (SEQ ID NO: 3) PGDG (SEQ ID NO: 20) FITSGYFD (SEQ ID NO: 33) FL-M13 GYTFTSY (SEQ ID NO: 3) PGDG (SEQ ID NO: 20) LITSGFFD (SEQ ID NO: 34) FL-M27 GYIFTSS (SEQ ID NO: 4) PGDG (SEQ ID NO: 20) GNGYLA (SEQ ID NO: 35) FL-M37 GYTFTNF (SEQ ID NO: 5) TYTG (SEQ ID NO: 21) YGSD (SEQ ID NO: 36) FL-M39 GYSFTDY (SEQ ID NO: 6) PSES (SEQ ID NO: 22) NGDAMD (SEQ ID NO: 37) FL-M40 GYSFTTY (SEQ ID NO: 7) PYDS (SEQ ID NO: 23) NGDALD (SEQ ID NO: 38) FL-M41 GYSFTTY (SEQ ID NO: 7) PYDN (SEQ ID NO: 24) NGDAMD (SEQ ID NO: 37) FL-M42 GYSFINY (SEQ ID NO: 8) PYES (SEQ ID NO: 25) NGDALD (SEQ ID NO: 38) FL-M43 GYSFTTY (SEQ ID NO: 7) PYDN (SEQ ID NO: 24) NGDALD (SEQ ID NO: 38) FL-M44 GYSFTTY (SEQ ID NO: 7) PYDN (SEQ ID NO: 24) NGDALD (SEQ ID NO: 38) FL-M45 GYSFINY (SEQ ID NO: 8) PYES (SEQ ID NO: 25) NGDALD (SEQ ID NO: 38) FL-M46 GYSFTTY (SEQ ID NO: 7) PYDN (SEQ ID NO: 24) NGDALD (SEQ ID NO: 38) FL-M51 GFSSSDY (SEQ ID NO: 9) DDNY (SEQ ID NO: 26) GGDYAMD (SEQ ID NO: 39) FL-M52 GYTFTDY (SEQ ID NO: 2) TYYG (SEQ ID NO: 27) YNGYYAMD (SEQ ID NO: 40) FL-M55 GYTLTTY (SEQ ID NO: 10) PGDG (SEQ ID NO: 20) LITTAMFD (SEQ ID NO: 41) FL-M58 GYSFTDY (SEQ ID NO: 6) PSES (SEQ ID NO: 22) NGDAMD (SEQ ID NO: 37) FL-M60 GFAFSNY (SEQ ID NO: 11) SGGG (SEQ ID NO: 28) SDRLLLALD (SEQ ID NO: 42) FL-M61 GYTFTEY (SEQ ID NO: 12) PNNG (SEQ ID NO: 29) IYDGYLYPLD (SEQ ID NO: 43) FL-M62 GYTFTEY (SEQ ID NO: 12) PNNG (SEQ ID NO: 29) IYDGYLYALD (SEQ ID NO: 44) FL-M65 GYSFIGY (SEQ ID NO: 13) PYNG (SEQ ID NO: 30) LRRGALD (SEQ ID NO: 45) FL-M68 GYTVTSF (SEQ ID NO: 14) PGDG (SEQ ID NO: 20) LITTGTID (SEQ ID NO: 46) FL-M69 GYTFTRF (SEQ ID NO: 15) PGDG (SEQ ID NO: 20) LITTANFD (SEQ ID NO: 47) FL-M71 GYSLTGY (SEQ ID NO: 16) PYSG (SEQ ID NO: 31) RGRENYFD (SEQ ID NO: 48) FL-M76 GFAFSSY (SEQ ID NO: 17) SGGG (SEQ ID NO: 28) YDNYFYAVD (SEQ ID NO: 49) FL-M77 GFAFSSY (SEQ ID NO: 17) SGGG (SEQ ID NO: 28) GDGYYFYAMD (SEQ ID NO: 50) Antibody name LC-CDR1 LC-CDR2 LC-CDR3 FL-M04 SQSVDYDGDSY (SEQ ID NO: 51) AAS (SEQ ID NO: 67) SNEDPY (SEQ ID NO: 77) FL-M06 SQSVDYDGDSY (SEQ ID NO: 51) LAS (SEQ ID NO: 68) SRELPP (SEQ ID NO: 78) FL-M07 SQSVDYDGDSY (SEQ ID NO: 51) AAS (SEQ ID NO: 67) SNEDPF (SEQ ID NO: 79) FL-M09 SESVDSYGNSF (SEQ ID NO: 52) LAS (SEQ ID NO: 68) NNEDRR (SEQ ID NO: 80) FL-M13 SESVDSYGNSF (SEQ ID NO: 52) LAS (SEQ ID NO: 68) NNEDHR (SEQ ID NO: 81) FL-M27 SSSVTY (SEQ ID NO: 53) DTF (SEQ ID NO: 69) WSSFPL (SEQ ID NO: 82) FL-M37 SSSVSF (SEQ ID NO: 54) DTS (SEQ ID NO: 70) WSSYPP (SEQ ID NO: 83) FL-M39 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WNSKF (SEQ ID NO: 84) FL-M40 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WSSKF (SEQ ID NO: 85) FL-M41 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WSSKF (SEQ ID NO: 85) FL-M42 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WSSKF (SEQ ID NO: 85) FL-M43 SSSVSD (SEQ ID NO: 55) GTS (SEQ ID NO: 72) WSSKF (SEQ ID NO: 85) FL-M44 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WSSKF (SEQ ID NO: 85) FL-M45 SSSVND (SEQ ID NO: 56) ATS (SEQ ID NO: 71) WSSKF (SEQ ID NO: 85) FL-M46 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WSSEF (SEQ ID NO: 86) FL-M51 SQNVGTN (SEQ ID NO: 57) SAS (SEQ ID NO: 73) YNSYPLY (SEQ ID NO: 87) FL-M52 SQDVNTA (SEQ ID NO: 58) SAS (SEQ ID NO: 73) HYSSPR (SEQ ID NO: 88) FL-M55 SKSVTTSDFSY (SEQ ID NO: 59) LAS (SEQ ID NO: 68) SNEDPW (SEQ ID NO: 89) FL-M58 SSSVSD (SEQ ID NO: 55) ATS (SEQ ID NO: 71) WSSNPP (SEQ ID NO: 90) FL-M60 SQTIDTW (SEQ ID NO: 60) AAT (SEQ ID NO: 74) LYGGPY (SEQ ID NO: 91) FL-M61 SQSISDY (SEQ ID NO: 61) YAS (SEQ ID NO: 75) GHSFPP (SEQ ID NO: 92) FL-M62 SQSISNN (SEQ ID NO: 62) YAS (SEQ ID NO: 75) SNSWPL (SEQ ID NO: 93) FL-M65 SQSVSND (SEQ ID NO: 63) SAS (SEQ ID NO: 73) DYSSPL (SEQ ID NO: 94) FL-M68 SQSVDYDGDSY (SEQ ID NO: 51) LAS (SEQ ID NO: 68) NNEDPR (SEQ ID NO: 95) FL-M69 SKSVSTSDFSY (SEQ ID NO: 64) LAS (SEQ ID NO: 68) SRELPR (SEQ ID NO: 96) FL-M71 SQDINSY (SEQ ID NO: 65) RAN (SEQ ID NO: 76) YDEFPN (SEQ ID NO: 97) FL-M76 SQTIGTW (SEQ ID NO: 66) AAT (SEQ ID NO: 74) LYSPPY (SEQ ID NO: 98) FL-M77 SQTIDTW (SEQ ID NO: 60) AAT (SEQ ID NO: 74) LYGGPY (SEQ ID NO: 91)

Table 3 Exemplary sequences Serial number Introduction sequence 99 FL-M04 V _H EVQLQQSGAELVRPGASVKISCKGSGYTFTKYTIHWVKQSHAKSLEWIGVISTYQGDANYNQKFKGKATMTVDKSSSTAYMELARLTSEDSAIYYCARFPDWDYAMDYWGQGTSVTVSS 100 FL-M06 V _H EVQLQQSGAELVRPGVSVKISCKGSGYTFTDYTIHWVKQSHAKSLEWIGVISTYNGDASYNQKFKGKATMTVDKSSNTAYMELARLTSEDSAIYYCARFPDWDYAMDYWGQGTSVTVSS 101 FL-M07 V _H EVQLQQSGAELVRPGASVKISCKGSGYTFTKYTIHWVKQSHAKSLEWIGVISTYQGDANYNQKFKGKATMTVDKSSSTAYMELARLTSEDSAIYYCARFPDWDYAMDYWGQGTTVTVSS 102 FL-M09 V _H EVQLQQSGPELVKPGASVKISCKASGYTFTSYDLNWVIQRPGQGLEWIGWIYPGDGSTKYNEKFKGKATLTADKSSSTAYMQLSSLTSEDSAVYFCARTFITSGYFDVWGAGTSVTVSS 103 FL-M13 V _H EVQLQQSGAELVMPGASLKISCKASGYTFTSYDINWVKQRPGQGLEWIGWIYPGDGSTKYNEKFKGKATLTADKSSSTAYMQLSSLTSENSAVYFCARTLITSGFFDVWGAGTSVTVSS 104 FL-M27 V _H EVQLQQSGAELARPGASVKLSCKASGYIFTSSWMQWVKQRPGQGLEWIGAIYPGDGDTRYTQKFRGKATLTADKSSSTSYIQLSSLASEDSAVYYCARGGNGYLAYWGQGTLVTVSA 105 FL-M37 V _H EVQLQQSGPELKKPGETVKISCKTSGYTFTNFGMNWVRQAPGKGLKWMGWINTYTGESTYADDFKGRFAFSLETSASTAYLQINNLKNEDMATYFCARDYGSDYWGQGTTLTVSS 106 FL-M39 V _H EVQLQESGAELVRPGSSVKISCKASGYSFTDYWMNWVKQRPGQGLEWIGMIHPSESETRLNQKFKDKATMTVDKSSSTAYMQLNRPTSEDSAVYYCARMNGDAMDYWGRGTSVTVSS 107 FL-M40 V _H EVQLAESGAELVRPGTSVKLSCKASGYSFTTYWMNWVKQRPGQGLEWIGMIHPYDSESRLNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCARMNGDALDYWGQGTSVTVSS 108 FL-M41 V _H EVQLQQSGAELVRPGASVKLSCKASGYSFTTYWMNWVKQRPGQGLEWIGMIHPYDNESRLNQKFRDKATLTVDKSSSTAYMQLTSPTSEDSAVYYCARMNGDAMDYWGQGTSVTVSS 109 FL-M42 V _H EVKLVESGAEVVRPGASVKLSCKASGYSFINYWMNWVKQRPGQGLEWIGMIHPYESETRLSQKFKDKATLTVDKSSTTAYMQLRSPTSEDSAVYYCARMNGDALDYWGQGTSVTVSS 110 FL-M43 V _H EVQLVETGAELVKPGASVKLSCKASGYSFTTYWMNWVKQRPGQGLEWIGMIHPYDNESRLSQKFRDKATLTVDKSSSTAYMQLTSPTSEDSAVYYCARMNGDALDYWGQGTSVTVSS 111 FL-M44 V _H EVQLVESGAELVRPGASVKLSCKASGYSFTTYWMNWVKQRPGQGLEWIGMIHPYDNESRLNQKFRDKATLTVDKSSSTAYMQLTSPTSEDSAVYYCARMNGDALDYWGQGTSVTVSS 112 FL-M45 V _H EVQLQQSGAELVRPGASVKLSCKASGYSFINYWMNWVKQRPGQGLEWIGMIHPYESETRLSQKFKDKATLTVDKSSTTAYMQLRSPTSEDSAVYYCARMNGDALDYWGQGTSVTVSS 113 FL-M46 V _H QVQLKQSGAELVRPGASVKLSCKASGYSFTTYWMNWVKQRPGQGLEWIGMIHPYDNESRLNQKFKDKATLTVDKSSNTAYMQLTSPTSEDSAVYYCARMNGDALDYWGQGTSVTVSS 114 FL-M51 V _H QVQLKQSGGGLVKPGGSLKLSCAASGFSSSDYYMFWVRQTPEKRLEWVATISDDNYYIHYLDSVKGRYTISRDNAKNNLYLQMNSLRSEDTAMYYCARWGGDYAMDYWGQGTSVTVSS 115 FL-M52 V _H EVKLEESGAELVRPGVSVKISCKGSGYTFTDYAMHWVKQSHAKSLEWIGVISTYYGDTTYNQKFKGKATMTVDKSSSTAYLDLARLTSEDSAIYYCARDYNGYYAMDYWGQGTSVTVSS 116 FL-M55 V _H EVQLLESGAELVKPGASVKLSCKASGYTLTTYDINWVRQRPEQGLEWIGWIFPGDGSTNYNEKFKGKATLTIDKSSSTAYMQLSRLTSEDSAVYFCARSLITTAMFDYWGQGTTLTVSS 117 FL-M58 V _H EVQLQQSGAELVRPGASVKLSCKASGYSFTDYWMNWVKQRPGQGLEWIGMIHPSESETRLNQKFKDKATLTVDKSSSTAYMQLSSPTSEDSAVYYCARMNGDAMDYWGQGTSVTVSS 118 FL-M60 V _H EVQLQQSGGGLVKPGGSLKFSCAASGFAFSNYDMSWVRQTPEKRLEWVAYISSGGGSTYYPDTVKGRFTISRDNAKNNLYLQMSSLKSEDTAMYYCARHSDRLLLALDYWGQGTSVTVSS 119 FL-M61 V _H QIQLLQSGPELVKPGASVKISCKTSGYTFTEYTMHWVKQSHGKSLEWIGGISPNNGYTTYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARPIYDGYLYPLDYWGQGTSVTVSS 120 FL-M62 V _H EVQLQQSGPELVKPGASVKISCKTSGYTFTEYTMHWVKQSHGKSLEWIGGISPNNGYTTYNQKFKGKATLTVDKSSSTAYMELRSLTSEDSAVYYCARPIYDGYLYALDYWGQGTSVTVSS 121 FL-M65 V _H EVQLKQSGPELVKPGGSLRISCTASGYSFIGYTMTWVRQSHGENLEWVGLINPYNGGTNYNQKFKDKATLTVDKSSNTAYMELLSLTSEDSAVYYCARSLRRGALDYWGQGTSVTVSS 122 FL-M68 V _H QVQLQQSGAELVKPGASVKLSCKASGYTVTSFDINWVRQRPEQGLEWIGWIFPGDGTSNYNEKFKGKATLTTDKSSSTAYMQLSRLTSEDSAVYFCARSLITTGTIDYWGQGTTVTVSS 123 FL-M69 V _H EVQLQQSGAELVKPGASVKLSCKASGYTFTRFDINWVRQRPEQGLEWIGWIFPGDGSTKYNEKFKGKATLTTDKSSTTAYMQLSRLTSEDSAVYFCARSLITTANFDYWGQGTTLTVSS 124 FL-M71 V _H QVQLQQSGAGLVKPGASMKISCKASGYSLTGYTMNWVKQSHGMNLEWIGLINPYSGGTNYNQKFRDKATLTVDKSSNTAYMELLSLTSEDSAVYYCARLRGRENYFDYWGQGTTLTVSS 125 FL-M76 V _H EVHLVESGGGLVKPGGSLKLSCAASGFAFSSYDMSWVRQSPEKRLQWVAFISSGGGSAYYSDTVKGRFIISRDNAKNTLYLQMSSLKSEDTAIYYCARHYDNYFYAVDYWGQGTSVTVSS 126 FL-M77 V _H EVHLVESGGGLVKPGGSLKLSCAASGFAFSSYDMSWFRQTPEKRLEWVAYISSGGGSTYYPDTVKGRFTISRDNAKNTLYLQMSSLKSEDTAMYYCARHGDGYYFYAMDYWGQGTSVTVSS 127 FL-M04 V _L DIVLSQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPYTFGGGTKLEIK 128 FL-M06 V _L DIVMTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYLASNLESGVPARFSGSGSGTDFTLNIHPVEEEDAATYYCQHSRELPPTFGSGTRLEIK 129 FL-M07 V _L DIVLTQSPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIYAASNLESGIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPFTFGSGTKLEIK 130 FL-M09 V _L DIQMMQSPASLAVSPGQRATISCRASESVDSYGNSFMHWYQQKPGQPPKLLIFLASNLESGVPARFSGSGSRTDFTLTIDPVEADDTATYYCQQNNEDRRTFGGGTKLEIK 131 FL-M13 V _L DIVLTQSPASLAVSLGQRATISCRASESVDSYGNSFMHWYQQKPGQPPKLLIFLASNLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDHRTFGGGTKLEIK 132 FL-M27 V _L DVVMTQTPAIMSASPGEKVTMTCSVSSSVTYMYWYQQKPGSSPRLLIYDTFNLASGVPVRFSGSGSGTSYSLTISRMEAEDAATYYCQQWSSFPLTFGAGTKLELK 133 FL-M37 V _L DIVLIQSPAIMSASPGEKVTMTCSASSSVSFMSWYQQKPGSSPRLWIYDTSALVSGVPARFSGSRSGTSYSLTISSMEAEDAATYYCQQWSSYPPTFGDGTRLEIK 134 FL-M39 V _L DIVLIQSPAILSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSDLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWNSKFTFGSGTKLEIK 135 FL-M40 V _L DIVLTQSPAILSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSDLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSSKFTFGSGTKLEIK 136 FL-M41 V _L QIVLTQSPAILSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSDLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSSKFTFGSGTKLEIK 137 FL-M42 V _L DIQMTQSPAIVSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSNLASGVPARFSGSGSGTSYSLTINRVEAEDAATYYCQQWSSKFTFGSGTKLEIK 138 FL-M43 V _L QIVLTQSPAILSASPGEKVTMTCRASSSVSDMHWYQQQPGSSPKPWIYGTSNLASGVPVRFSGSGSGTSYSLTISRVEPEDAATYYCQQWSSKFTFGSGTKLEIK 139 FL-M44 V _L DIVMTQSPAIVSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSDLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSSKFTFGSGTKLEIK 140 FL-M45 V _L DIVLTQSPAILSASPGEKVTMTCRASSSVNDMHWYQQKPGSSPKPWIYATSNLASGVPTRFSGSGSGTSYSLTISRVEAEDAATYYCQQWSSKFTFGSGTKLEIK 141 FL-M46 V _L DIVLTQSPAILSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSNLASGVPARFTGSGSGTSYSLTISRVEAEDAATYYCQQWSSEFTFGSGTKLEIK 142 FL-M51 V _L DIVMTQSPKFMSTSVGDRVSVTCKASQNVGTNVVWYQQKPGQSPKVLIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEYFCQQYNSYPLYTFGGGTKLEIK 143 FL-M52 V _L DIQMMQSPKFMSTSVGDRVSIACKASQDVNTAVAWYQQKPGQSPKLLMYSASFRYTGVPDRFTGSGSGTDFTFTISSVQAEDLAVYYCQQHYSSPRTFGGGTKLEIK 144 FL-M55 V _L DIKMTQTPASLAVSLGQRATISCRASKSVTTSDFSYIHWYQQKPGLPPKLLIFLASHLESGVPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK 145 FL-M58 V _L EIVLTQSPAILSASPGEKVTMTCRASSSVSDMHWYQQKPGSSPKPWIYATSDLASGVPARFSGSGSGTSYSLTISRVEAEDAATYYCQQWSSNPPTFGGGTKLEIK 146 FL-M60 V _L DIVMTQTPASQSASLGESVTITCLASQTIDTWLAWYQQKPGKSPQLLIYAATNLADGVPSRFSGSGSGTKFSLKISRLQAEDFVTYYCQQLYGGPYTFGGGTKLEIK 147 FL-M61 V _L QNVLTQSPATLSVTPGDRVSLSCRASQSISDYLHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGSDFTLSINSVEPEDVGVYYCQNGHSFPPTFGAGTKLELK 148 FL-M62 V _L DIVMSQSPATLSVTPGDSVSLSCRASQSISNNLHWYQQKSHESPRLLIKYASQSISGIPSRFSGSGSGTDFTLSINSVETEDFGMYFCQQSNSWPLTFGAGTKLELK 149 FL-M65 V _L DIVLTQSPKFLLVSAGDRVTITCKASQSVSNDVAWYQQKPGQSPKLLIYSASNRYTGVPDRFTGSGYGTDFTFTISTVQAEDLAVYFCQQDYSSPLTFGAGTKLELK 150 FL-M68 V _L DIKMTQTPASLAVSLGQRATISCKASQSVDYDGDSYMNWYQQKPGQPPKLLIFLASYLESGVPARFSGSGSRTDFTLTIDPVEADDAATYYCQQNNEDPRTFGGGTKLEIK 151 FL-M69 V _L QIVLTQSPASLAVSLGQRATISCRASKSVSTSDFSYIHWYQQKPGQPPKLLIFLASHLESGVPARFSGSGSGTDFTLNIHPVEEEDAATYYCQHSRELPRTFGGGTKLEIK 152 FL-M71 V _L DIVMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRANRMVDGVPPRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDEFPNTFGGGTKLEIK 153 FL-M76 V _L DILLTQSPASQSASLGESVTITCLASQTIGTWLAWYQQKPGKSPQLLIYAATSLADGVPSRFSGSGSGTKFSFKISSLQAEDFVSYYCQQLYSPPYTFGGGTKLEIK 154 FL-M77 V _L DIVMTQSPASQSASLGESVTITCLASQTIDTWLAWYQQKPGKSPQLLIYAATNLADGVPSRFSGSGSGTKFSLKISRLQAEDFVSYYCQQLYGGPYTFGGGTKLEIK 155 IgG1 heavy chain constant region ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVS NKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 156 IgG4 heavy chain constant region ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNK GLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 157 Light chain constant region (kappa) RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 158 Light chain constant region (lambda) GQPKAAPSVTLFPPSSEELQANKATLVCLISDFYPGAVTVAWKADSSPVKAGVETTTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 159 Human FasL MQQPFNYPYPQIYWVDSSASSPWAPPGTVLPCPTSVPRRPGQRRPPPPPPPLPLPPPPPPPLPLPLPKKRGNHSTGLCLLVMFFMVLVALVGLGLGMFQLFHLQKELAELRESTSQMHTASSLEKQIGHPSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNS KYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL 160 Human FasL extracellular domain PSPPPEKKELRKVAHLTGKSNSRSMPLEWEDTYGIVLLSGVKYKKGGLVINETGLYFVYSKVYFRGQSCNNLPLSHKVYMRNSKYPQDLVMMEGKMMSYCTTGQMWARSSYLGAVFNLTSADHLYVNVSELSLVNFEESQTFFGLYKL

Full-length anti-FasL antibody

In some embodiments, the aforementioned anti-FasL antibody system is a full-length anti-FasL antibody. In some embodiments, the aforementioned full-length anti-FasL antibody system is IgA, IgD, IgE, IgG or IgM. In some embodiments, the aforementioned full-length anti-FasL antibody comprises an IgG constant region, such as the constant region of IgG1, IgG2, IgG3, IgG4 or variants thereof. In some embodiments, the aforementioned full-length anti-FasL antibody comprises a lambda light chain constant region. In some embodiments, the aforementioned full-length anti-FasL antibody comprises a kappa light chain constant region. In some embodiments, the aforementioned full-length anti-FasL antibody is a full-length human anti-FasL antibody. In some embodiments, the aforementioned full-length anti-FasL antibody comprises a mouse immunoglobulin Fc sequence. In some embodiments, the aforementioned full-length anti-FasL antibody includes an Fc sequence that has been changed or otherwise changed, such that it has enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity ( CDC) effector function.

Therefore, for example, in some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, and the aforementioned anti-FasL antibody specifically binds to FasL. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG2 constant region is provided, and the aforementioned anti-FasL antibody specifically binds to FasL. In some embodiments, the aforementioned IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG3 constant region is provided, and the aforementioned anti-FasL antibody specifically binds to FasL. In some embodiments, the aforementioned IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, and the aforementioned anti-FasL antibody specifically binds to FasL. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which includes SEQ ID NOs: the amino acid sequence shown in any one of 1-17, HC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 18-31, and HC-CDR3, which includes SEQ ID The amino acid sequence shown in any one of NOs: 32-50, or a variant of the aforementioned heavy chain variable domain, whose HC-CDR sequence contains at most about 5 (for example, 1, 2, 3, 4 or 5 A) substitution of amino acids; and b) light chain variable domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence shown in any one of SEQ ID NOs: 51-66 , LC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 67-76, and LC-CDR3, which includes the amino acid sequence shown in any one of SEQ ID NOs: 77-98, Or a variant of the aforementioned light chain variable domain, the LC-CDR sequence of which contains at most about 5 (for example, 1, 2, 3, 4 or 5) amino acid substitutions. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which includes SEQ ID The amino acid sequence shown in any one of NOs: 1-17, HC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 18-31, and HC-CDR3, which includes SEQ ID NOs : The amino acid sequence shown in any one of 32-50, or a variant of the aforementioned heavy chain variable domain, whose HC-CDR sequence contains at most about 5 (for example, 1, 2, 3, 4 or 5 ) amino acid substitution; and b) light chain variable domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence shown in any one of SEQ ID NOs: 51-66, LC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 67-76, and LC-CDR3, which includes the amino acid sequence shown in any one of SEQ ID NOs: 77-98, or the aforementioned Variants of the light chain variable domain include substitutions of up to about 5 (eg, 1, 2, 3, 4 or 5) amino acids in the LC-CDR sequence. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which includes SEQ ID NOs: the amino acid sequence shown in any one of 1-17, HC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 18-31, and HC-CDR3, which includes SEQ ID The amino acid sequence shown in any one of NOs: 32-50; and b) the light chain variable domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes any of SEQ ID NOs: 51-66 The amino acid sequence shown in one, LC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 67-76, and LC-CDR3, which includes any one of SEQ ID NOs: 77-98 The amino acid sequence shown. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which includes SEQ ID NOs: The amino acid sequence shown in any one of 1-17, HC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 18-31, and HC-CDR3, which includes SEQ ID The amino acid sequence shown in any one of NOs: 32-50; and b) the light chain variable domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes any of SEQ ID NOs: 51-66 The amino acid sequence shown in one, LC-CDR2, which includes the amino acid sequence shown in any one of SEQ ID NOs: 67-76, and LC-CDR3, which includes any one of SEQ ID NOs: 77-98 The amino acid sequence shown. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 77. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 19, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 78. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 79. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 3, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 33; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 80. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 3, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 34; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 81. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 4, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 35; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 53, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 69, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 82. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 5, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 21, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 36; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 54, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 70, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 83. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 6, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 84. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 23, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 72, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 56, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 86. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 9, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 26, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 39; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 57, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 87. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 27, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 40; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 58, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 88. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 10, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 41; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 59, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 89. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 6, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 90. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 11, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 42; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 91. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 43; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 61, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 92. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 44; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 62, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 93. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 13, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 30, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 45; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 63, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 94. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 14, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 46; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 95. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 15, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 47; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 64, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 96. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 16, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 31, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 48; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 65, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 76, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 97. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 49; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 66, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 98. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 50; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 91. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 77. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 19, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 78. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 79. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 3, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 33; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 80. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 3, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 34; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 81. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 4, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 35; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 53, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 69, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 82. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 5, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 21, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 36; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 54, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 70, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 83. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 6, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 84. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 23, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 72, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 56, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 85. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 86. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 9, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 26, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 39; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 57, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 87. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 27, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 40; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 58, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 88. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 10, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 41; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 59, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 89. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 6, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 90. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 11, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 42; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 91. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 43; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 61, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 92. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 44; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 62, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 93. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 13, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 30, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 45; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 63, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 94. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 14, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 46; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 95. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 15, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 47; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 64, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 96. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 16, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 31, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 48; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 65, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 76, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 97. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 49; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 66, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 98. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the aforementioned anti-FasL antibody includes: a) a heavy chain variable domain, and the aforementioned heavy chain variable domain includes: HC-CDR1, which contains an amine The amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 50; and b) light chain variable structure Domain, the aforementioned light chain variable domain includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes Amino acid sequence SEQ ID NO: 91. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: a heavy chain variable domain ( _VH ), the aforementioned _VH comprising any one of SEQ ID NOs: 99-126 The amino acid sequence shown in any one of SEQ ID NOs: 99-126 or a variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%) of the amino acid sequence shown in any one of SEQ ID NOs: 99-126. %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), the aforementioned V _L comprising the amino acid shown in any one of SEQ ID NOs: 127-154 Sequence or variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG2 constant region is provided, wherein the anti-FasL antibody comprises: a heavy chain variable domain ( _VH ), the aforementioned _VH comprising any one of SEQ ID NOs: 99-126 The amino acid sequence shown in any one of SEQ ID NOs: 99-126 or a variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%) of the amino acid sequence shown in any one of SEQ ID NOs: 99-126. %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), the aforementioned V _L comprising the amino acid shown in any one of SEQ ID NOs: 127-154 Sequence or variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity. In some embodiments, the aforementioned IgG2 is human IgG2. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG3 constant region is provided, wherein the anti-FasL antibody comprises: a heavy chain variable domain ( _VH ), the aforementioned _VH comprising any one of SEQ ID NOs: 99-126 The amino acid sequence shown in any one of SEQ ID NOs: 99-126 or a variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%) of the amino acid sequence shown in any one of SEQ ID NOs: 99-126. %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), the aforementioned V _L comprising the amino acid shown in any one of SEQ ID NOs: 127-154 Sequence or variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity. In some embodiments, the aforementioned IgG3 is human IgG3. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: a heavy chain variable domain ( _VH ), the aforementioned _VH comprising any one of SEQ ID NOs: 99-126 The amino acid sequence shown in any one of SEQ ID NOs: 99-126 or a variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%) of the amino acid sequence shown in any one of SEQ ID NOs: 99-126. %, 96%, 97%, 98% or 99%) sequence identity; and a light chain variable domain (V _L ), the aforementioned V _L comprising the amino acid shown in any one of SEQ ID NOs: 127-154 Sequence or variant thereof, the aforementioned variant has at least about 80% (such as at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99%) sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: a heavy chain variable domain ( _VH ), the aforementioned ( _VH ) comprising any of SEQ ID NOs: 99-126 The amino acid sequence shown in A, and the light chain variable domain (V _L ), the aforementioned (V _L ) includes the amino acid sequence shown in any one of SEQ ID NOs: 127-154. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: a heavy chain variable domain ( _VH ), the aforementioned _VH comprising any one of SEQ ID NOs: 99-126 The amino acid sequence shown in SEQ ID NOs: 127-154, and the light chain variable domain (V _L ), the aforementioned V _L includes the amino acid sequence shown in any one of SEQ ID NOs: 127-154. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 99 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 99 or a variant thereof. The sequence SEQ ID NO: 99 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 127 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 127. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody includes: _VH , which includes the amino acid sequence SEQ ID NO: 100 or a variant thereof, the aforementioned variant being the same as the amino acid sequence SEQ ID NO: 100 or a variant thereof. The sequence SEQ ID NO: 100 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 128 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 128. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 101 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 101 or a variant thereof. The sequence SEQ ID NO: 101 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 129 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 129. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 102 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 102 or a variant thereof. The sequence SEQ ID NO: 102 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 130 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 130. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 103 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 103 or a variant thereof. The sequence SEQ ID NO: 103 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 131 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 131. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 104 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 104 or a variant thereof. The sequence SEQ ID NO: 104 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 132 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 132. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 105 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 105 or a variant thereof. The sequence SEQ ID NO: 105 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 133 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 133. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 106 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 106 or a variant thereof. The sequence SEQ ID NO: 106 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 134 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 134. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 107 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 107 or a variant thereof. The sequence SEQ ID NO: 107 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 135 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 135. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 108 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 108 or a variant thereof. The sequence SEQ ID NO: 108 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 136 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 136. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 109 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 109 or a variant thereof. The sequence SEQ ID NO: 109 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 137 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 137. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 110 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 110 or a variant thereof. The sequence SEQ ID NO: 110 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 138 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 138. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody includes: _VH , which includes the amino acid sequence SEQ ID NO: 111 or a variant thereof, the aforementioned variant being the same as the amino acid sequence SEQ ID NO: 111 or a variant thereof. The sequence SEQ ID NO: 111 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 139 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 139. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 112 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 112 or a variant thereof. The sequence SEQ ID NO: 112 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 140 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 140. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 113 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 113 or a variant thereof. The sequence SEQ ID NO: 113 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 141 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 141. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 114 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 114 or a variant thereof. The sequence SEQ ID NO: 114 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 142 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 142. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 115 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 115 or a variant thereof. The sequence SEQ ID NO: 115 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 143 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 143. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 116 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 116 or a variant thereof. The sequence SEQ ID NO: 116 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 144 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 144. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 117 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 117 or a variant thereof. The sequence SEQ ID NO: 117 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 145 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 145. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 118 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 118 or a variant thereof. The sequence SEQ ID NO: 118 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 146 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 146. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 119 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 119 or a variant thereof. The sequence SEQ ID NO: 119 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 147 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 147. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 120 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 120 or a variant thereof. The sequence SEQ ID NO: 120 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 148 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 148. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 121 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 121 or a variant thereof. The sequence SEQ ID NO: 121 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 149 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 149. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 122 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 122 or a variant thereof. The sequence SEQ ID NO: 122 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 150 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 150. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 123 or a variant thereof, the aforementioned variant being identical to the amino acid sequence The sequence SEQ ID NO: 123 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 151 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 151. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 124 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 124 or a variant thereof. The sequence SEQ ID NO: 124 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 152 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 152. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 125 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 125 or a variant thereof. The sequence SEQ ID NO: 125 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 153 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 153. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG1 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 126 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 126 or a variant thereof. The sequence SEQ ID NO: 126 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 154 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 154. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 99 or a variant thereof, the aforementioned variant being identical to the amino acid sequence The sequence SEQ ID NO: 99 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 127 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 127. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody includes: _VH , which includes the amino acid sequence SEQ ID NO: 100 or a variant thereof, the aforementioned variant being the same as the amino acid sequence SEQ ID NO: 100 or a variant thereof. The sequence SEQ ID NO: 100 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 128 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 128. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 101 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 101 or a variant thereof. The sequence SEQ ID NO: 101 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 129 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 129. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 102 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 102 or a variant thereof. The sequence SEQ ID NO: 102 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 130 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 130. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 103 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 103 or a variant thereof. The sequence SEQ ID NO: 103 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 131 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 131. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 104 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 104 or a variant thereof. The sequence SEQ ID NO: 104 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 132 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 132. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 105 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 105 or a variant thereof. The sequence SEQ ID NO: 105 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 133 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 133. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 106 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 106 or a variant thereof. The sequence SEQ ID NO: 106 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 134 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 134. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 107 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 107 or a variant thereof. The sequence SEQ ID NO: 107 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 135 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 135. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 108 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 108 or a variant thereof. The sequence SEQ ID NO: 108 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 136 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 136. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 109 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 109 or a variant thereof. The sequence SEQ ID NO: 109 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 137 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 137. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 110 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 110 or a variant thereof. The sequence SEQ ID NO: 110 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 138 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 138. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 111 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 111 or a variant thereof. The sequence SEQ ID NO: 111 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 139 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 139. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 112 or a variant thereof, the aforementioned variant being the same as the amino acid sequence SEQ ID NO: 112 or a variant thereof. The sequence SEQ ID NO: 112 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 140 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 140. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 113 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 113 or a variant thereof. The sequence SEQ ID NO: 113 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 141 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 141. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 114 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 114 or a variant thereof. The sequence SEQ ID NO: 114 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 142 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 142. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 115 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 115 or a variant thereof. The sequence SEQ ID NO: 115 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 143 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 143. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 116 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 116 or a variant thereof. The sequence SEQ ID NO: 116 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 144 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 144. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 117 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 117 or a variant thereof. The sequence SEQ ID NO: 117 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 145 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 145. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 118 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 118 or a variant thereof. The sequence SEQ ID NO: 118 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 146 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 146. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 119 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 119 or a variant thereof. The sequence SEQ ID NO: 119 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 147 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 147. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 120 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 120 or a variant thereof. The sequence SEQ ID NO: 120 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 148 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 148. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 121 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 121 or a variant thereof. The sequence SEQ ID NO: 121 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 149 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 149. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 122 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 122 or a variant thereof. The sequence SEQ ID NO: 122 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 150 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 150. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 123 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 123 or a variant thereof. The sequence SEQ ID NO: 123 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 151 or a variant thereof, which has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 151. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 124 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 124 or a variant thereof. The sequence SEQ ID NO: 124 has at least about 80% sequence identity; and V _L includes the amino acid sequence SEQ ID NO: 152 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 152. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 125 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 125 or a variant thereof. The sequence SEQ ID NO: 125 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 153 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 153. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, a full-length anti-FasL antibody comprising an IgG4 constant region is provided, wherein the anti-FasL antibody comprises: V _H comprising the amino acid sequence SEQ ID NO: 126 or a variant thereof, the aforementioned variant being identical to the amino acid sequence SEQ ID NO: 126 or a variant thereof. The sequence SEQ ID NO: 126 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence SEQ ID NO: 154 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence SEQ ID NO: 154. Approximately 80% sequence identity. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156 and the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

binding affinity

Binding affinity is expressed as Kd, Koff, Kon or Ka. As used in this specification, the term Koff refers to the rate constant for the dissociation of an antibody from an antigen/antibody complex, as measured by a kinetic selection device. The term Kon refers to the binding rate constant at which an antibody binds to an antigen to form an antigen/antibody complex. The equilibrium dissociation constant Kd used in this specification refers to the dissociation constant when a specific antibody-antigen interacts. It refers to the antigen concentration required when the antigen occupies half of all antibody binding sites in the antibody molecule solution and reaches equilibrium, which is equal to Koff/ Kon. The determination of Kd assumes that all bound molecules are in solution. In the case of antibodies bound to the cell wall, such as in yeast expression systems, the corresponding equilibrium dissociation rate constant is expressed as EC50, which is a good approximation of Kd. The affinity binding constant Ka is the reciprocal of the dissociation constant Kd.

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

The binding specificity of the antibody can be experimentally determined by methods known in the art to which the present invention belongs. These methods include, but are not limited to, Western blots, ELISA-, RIA-, ECL-, IRMA-, EIA-, BIAcore testing and peptide scanning.

In some embodiments, the aforementioned anti-FasL antibody specifically binds to the FasL target, and its Kd value is 10 ^-7 M to 10 ^-13 M (for example, 10 ^-7 M to 10 ^-13 M, 10 ^-8 M to 10 ^-13 M, 10 ^-9 M to 10 ^-13 M or 10 ^-10 M to 10 ^-12 M). Therefore, in some embodiments, the Kd value of the binding between the anti-FasL antibody and FasL is 10 ^-7 M to 10 ^-13 M, 1×10 ^-7 M to 5×10 ^-13 M, 10 ^-7 M to 10 ^-12 M, 10 ^-7 M to 10 ^-11 M, 10 ^-7 M to 10 ^-10 M, 10 ^-7 M to 10 ^-9 M, 10 ^{-8 M to 10 -13 M} , 1×10 ^-8 M to 5×10 ^-13 M, 10 ^-8 M to 10 ^-12 M, 10 ^-8 M to 10 ^-11 M, 10 ^-8 M to 10 ^-10 M, 10 ^-8 M to 10 ^-9 M, 5× 10 ^-9 M to 1×10 ^-13 M, 5×10 ^-9 M to 1×10 ^-12 M, 5×10 ^-9 M to 1×10 ^-11 M, 5×10 ^-9 M to 1×10 ^-10 M, 10 ^-9 M to 10 ^-13 M, 10 ^-9 M to 10 ^-12 M, 10 ^-9 M to 10 ^-11 M, 10 ^-9 M to 10 ^-10 M, 5×10 ^-10 M to 1×10 ^-13 M, 5×10 ^-10 M to 1×10 ^-12 M, 5×10 ^-10 M to 1×10 ^-11 M, 10 ^-10 M to 10 ^-13 M, 1×10 ^{- 10} M to 5×10 ^-13 M, 1×10 ^-10 M to 1×10 ^-12 M, 1×10 ^-10 M to 5×10 ^-12 M, 1×10 ^-10 M to 1×10 ^-11 M, 10 ^-11 M to 10 ^-13 M, 1×10 ^-11 M to 5×10 ^-13 M, 10 ^-11 M to 10 ^-12 M, 10 ^-12 M to 10 ^-13 M. In some embodiments, the Kd value of the binding between the anti-FasL antibody and FasL is 10 ^-7 M to 10 ^-13 M.

In some embodiments, the Kd value of the anti-FasL antibody binding to the non-target is higher than the Kd value of the anti-FasL antibody binding to the target. In addition, in some embodiments cited in this specification, the anti-FasL antibody binds to the target (for example, , FasL) has a higher binding affinity than the anti-FasL antibody to the non-target. In some embodiments, non-target refers to an antigen other than FasL. In some embodiments, the Kd value of the anti-FasL antibody (against FasL) binding to the non-FasL target is at least 10 times different, such as 10-100 times, 100-1000 times, 10 ³ -10 ⁴ times, 10 ⁴ -10 ⁵ times, 10 ⁵ -10 ^{6 times} , 10 ⁶ -10 ⁷ times, 10 ⁷ -10 8 times, 10 ⁸ -10 ⁹ times, 10 ⁹ -10 ¹⁰ times, 10 ¹⁰ -10 ¹¹ times, 10 ¹¹ -10 ¹² times.

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

In some embodiments, when it is mentioned that the anti-FasL antibody specifically recognizes the FasL target with high binding affinity and binds to the non-target with low binding affinity, the Kd value of the aforementioned anti-FasL antibody binding to the FasL target is 10 ^{- 7} M to 10 ^-13 M (for example, 10 ^-7 M to 10 ^-13 M, 10 ^-8 M to 10 ^-13 M, 10 ^-9 M to 10 ^-13 M, 10 ^-10 M to 10 ^-12 M), And the Kd value for binding to non-target is 10 ^-1 M to 10 ^-6 M (for example, 10 ^-1 M to 10 ^-6 M, 10 ^-1 M to 10 ^-5 M, 10 ^-2 M to 10 ^-4 M ).

In some embodiments, when it is mentioned that an anti-FasL antibody specifically recognizes FasL, the binding affinity of the aforementioned anti-FasL antibody is compared with the binding affinity of a control anti-FasL antibody (such as 119-4A or APG101 or MAB126-100). In some embodiments, the Kd value of the binding between the control anti-FasL antibody and FasL can be at least 2 times, such as 2 times, 3 times, or 4 times the Kd value of the binding between the anti-FasL antibody and FasL of the present invention. , 5 times, 6 times, 7 times, 8 times, 9 times, 10 times, 10-100 times, 100-1000 times, 10 ³ -10 ⁴ times.

nucleic acid

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

Also contemplated herein are isolated host cells containing anti-FasL antibodies, isolated nucleic acids encoding anti-FasL antibody polypeptide components, or vectors containing nucleic acids encoding anti-FasL antibody polypeptide components described herein.

Variants of these nucleic acid sequences are also encompassed by the present invention. For example, a variant includes a nucleotide sequence that hybridizes under at least moderately stringent hybridization conditions to a nucleic acid sequence encoding an anti-FasL antibody of the invention.

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

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

The nucleic acid of the present invention can also be used for nucleic acid immunization and gene therapy by using standard gene delivery means. Nucleic acid delivery methods are known in the art to which this invention pertains. See, for example, U.S. Patent Nos. 5,399,346, 5,580,859, and 5,589,466, the entire contents of which are incorporated herein by reference. In some embodiments, the present invention also provides gene therapy vectors.

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

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

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

Other promoter elements, such as enhancers, regulate the frequency of transcription initiation. Usually they are located 30-110 bp upstream of the start site, although recently many promoters have been found to also contain functional elements downstream of the start site. The spacing between promoter elements is usually flexible, so that promoter function can be maintained when elements are interchanged or moved with each other. In the thymidine kinase (tk) promoter, activity does not begin to decrease until the spacing between promoter elements increases to 50 bp.

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

In some embodiments, the expression of anti-FasL antibodies is inducible. In some embodiments, the nucleic acid sequence encoding the anti-FasL antibody is operably linked to an inducible promoter, including any inducible promoter described in this specification.

inducible promoter

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

An exemplary inducible promoter system employed in the present invention is the Tet system. The system is based on the Tet system described by Gossen et al. (1993). In an exemplary embodiment, the target polynucleotide is controlled by a promoter containing one or more Tet operator (TetO) sites. In the inactive state, Tet repressor (TetR) binds to the TetO site and inhibits promoter transcription. In the activated state, for example, in the presence of inducers such as tetracycline (Tc), anhydrotetracycline, doxycycline (Dox) or their active analogs, the inducer causes TetR to be released from TetO, resulting in transcription. Doxycycline is a member of the tetracycline antibiotic family, its chemical name is 1-dimethylamino-2,4a,5,7-pentahydroxy-11-methyl-4,6-dioxy-1,4a ,11,11a,12,12a-hexahydrotetraene-3-methamide.

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

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

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

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

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

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

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

Methods for introducing genes into cells and expressing them are known in the technical field to which this invention belongs. In the context of expression vectors, vectors can be readily introduced into host cells, such as mammalian cells, bacteria, yeast or insect cells, by any method known to the art of the present invention. For example, expression vectors can be introduced into host cells by physical, chemical or biological methods.

Physical methods of introducing polynucleotides into host cells include calcium phosphate precipitation, lipofection, biolistic methods, microinjection, electroporation, and the like. Methods for preparing cells containing vectors and/or exogenous nucleic acids are well known in the art to which this invention pertains. See, for example, Green and Sambrook (2013, Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York). In some embodiments, the polynucleotide is introduced into the host cell by calcium phosphate transfection.

Biological methods for introducing polynucleotides of interest into host cells include the use of DNA and RNA vectors. Viral vectors, especially retroviral vectors, have become the most widely used method for inserting genes into mammalian cells, such as human cells. Other viral vectors can be derived from lentivirus, poxvirus, herpes simplex virus type 1, adenovirus, adeno-associated virus, etc. See, for example, US Patent Nos. 5,350,674 and 5,585,362.

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

Where non-viral delivery systems are used, an exemplary delivery vehicle is liposomes. Consider using lipid formulations to introduce nucleic acids into host cells (in vitro, ex vivo, or in vivo). In another aspect, the aforementioned nucleic acid can be combined with a lipid. Nucleic acids bound to lipids can be packaged into the aqueous interior of liposomes, spread within the lipid bilayer of liposomes, connected to liposomes through linking molecules that bind to liposomes and oligonucleotides, and embedded in liposomes. , form complexes with liposomes, be dispersed in a solution containing lipids, mixed with lipids, combined with lipids, suspended in lipids, contained in or mixed with micelles, or otherwise combined with lipids. Lipid, lipid/DNA or lipid/expression vehicle related compositions are not limited to any particular structure in solution. For example, they may exist in bilayer structures, in micelles or in "collapsed" structures. They can also be simply dispersed in a solution and may form aggregates of uneven size or shape. Lipids are fatty substances that can be naturally occurring or synthetic lipids. For example, lipids include fat droplets that occur naturally in the cytoplasm, as well as a class of compounds containing long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, aminoalcohols, and aldehydes.

Regardless of the method used to introduce exogenous nucleic acid into a host cell or otherwise expose the cell to the inhibitor of the invention, a variety of experiments can be performed to confirm that the recombinant DNA sequence is present in the host cell. Such experiments include, for example, "molecular biology" experiments that are well known to those of ordinary skill in the art to which this invention pertains. For example, Southern and Northern blotting, RT-PCR and PCR; "biochemical" experiments, such as detecting the presence or absence of a specific polypeptide, such as by immunological methods (ELISAs and Western blots) or by the experiments described in this specification Any identification falls within the scope of the present invention.

Preparation of anti-FasL antibodies

In some embodiments, the aforementioned anti-FasL antibody system monoclonal antibody may be derived from a monoclonal antibody. In some embodiments, the aforementioned anti-FasL antibody includes _VH and _VL derived from monoclonal antibodies, or variants thereof. In some embodiments, the aforementioned anti-FasL antibody further includes CH1 and CL regions from monoclonal antibodies, or variants thereof. Monoclonal antibodies can be prepared using methods known in the technical field of the present invention, including hybridoma cell methods, phage display methods, or recombinant DNA methods. Additionally, exemplary phage display methods are described in this specification and in the Examples below.

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

In some embodiments, the immortalized cell lines are effectively fused, and the selected antibody-producing cells ensure high-level and stable expression of the antibodies and are sensitive to certain media, such as HAT media. In some embodiments, the immortal cell line is a mouse myeloma cell line, which can be obtained from, for example, the Salk Cell Collection in San Diego, California, and the American Type Culture Collection in Manassas, Virginia. The use of human myeloma and mouse-human hybrid myeloma cell lines for the preparation of human monoclonal antibodies is also described.

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

After the desired hybridoma cells are identified, the target clones can be subcultured by limiting dilution and cultured by standard methods. Suitable media for this purpose include, for example, modified Eagle's medium (DMEM) and RPMI-1640 medium. Alternatively, hybridoma cells can be grown in mammals in the form of ascites fluid.

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

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

In some phage display methods, all components of the V _H and V _L genes are separately selected by polymerase chain reaction (PCR) and randomly recombined in a phage library, and then phages that can bind the antigen are screened, such as Winter et al., Ann. Rev. Immunol., 12: 433-455 (1994). Phages typically display antibody fragments as scFv fragments or as Fab fragments. Immunogenically derived library phages provide high-affinity antibodies against immunogens without the need for hybridoma cell construction. Alternatively, natural libraries (e.g. from humans) can be cloned to provide a single source of antibodies against multiple non-self-antigens as well as self-antigens without the need for any immunization, as in Griffiths et al., EMBO J, 12: 725-734 (1993 ) as stated in. Finally, natural libraries can also be prepared by selecting non-recombinant V-gene fragments from stem cells, using PCR primers containing random sequences to encode the CDR3 hypervariable region, and completing recombination in vitro, such as Hoogenboom and Winter, J. Mol. Biol., 227: 381-388 (1992). Patent publications describing human antibody phage libraries include, for example, U.S. Patent No. 5,750,373 and U.S. Patent Publication Nos. 2005/0079574, 2005/0119455, 2005/0266000, 2007/0117126, 2007/0160598, 2007/0237764, 2007/ 0292936 and 2009/0002360.

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

Colonization of phages with high affinity for target FasL can be screened by iterative binding of phage to target FasL bound to a solid support (such as beads for solution panning or for cell panning). mammalian cells), followed by removal of unbound phage and lysis of specifically bound phage. Subsequently, the bound phage are lysed, selected, and used to infect suitable host cells, such as E. coli XL1-Blue, for expression and purification. Phage colonies that specifically bind FasL can be enriched by multiple rounds of panning (eg, 2, 3, 4, 5, 6 or more rounds), such as solution panning, cell panning, or a combination of both. The specific binding of the enriched phage selection to the target FasL can be detected by any method known in the art of the present invention, including, for example, ELISA and FACS.

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

The human antibody V gene library (V _H and V _K fragments) was obtained by PCR using a set of degenerate primers (Sblattero, D. and Bradbury, A. Immunotechnology 3, 271-278 1998). PCR templates were derived from commercially available RNA or cDNA, including PBMC, spleen, lymph node, bone marrow, and tonsils. Independent V _H and V _K PCR libraries were combined and assembled into scFv formats by overlap extension PCR (Sheets, MD et al, Proc. Natl. Acad. Sci. USA 95, 6157–6162 1998). To construct a yeast scFv display library, the resulting scFv PCR products were cloned into yeast display plasmids in yeast by homologous recombination. (Chao, G, et al, Nat Protoc. 2006;1(2):755-68. Miller KD, et al. Current Protocols in Cytometry 4.7.1-4.7.30, 2008).

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

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

Monoclonal antibodies can also be prepared by recombinant DNA methods, such as those described in U.S. Patent No. 4,816,567. DNA encoding the monoclonal antibodies of the present invention can be easily isolated and sequenced by conventional methods (for example, by oligonucleotide probes that specifically bind to genes encoding the light and heavy chains of murine antibodies). The hybridoma cells as described above or the FasL-specific phage selection of the present invention can be used as the source of this DNA. After isolation, the DNA can be placed in an expression vector, and then the vector is transfected into host cells, such as simian COS cells, Chinese hamster ovary cancer (CHO) cells, or myeloma cells that do not produce immunoglobulins, to obtain the expression in the recombinant host. Monoclonal antibodies synthesized in cells. The aforementioned DNA can also be modified, for example, by replacing the human heavy and light chain constant regions with coding sequences and/or by replacing homologous non-human sequences with framework regions (U.S. Patent No. 4,816,567; Morrison et al., supra), or by All or part of the coding sequence for a non-immunoglobulin polypeptide is covalently linked to the coding sequence for an immunoglobulin. This non-immunoglobulin polypeptide can replace the constant region of the antibody of the present invention, or can replace an antigen-binding site in the variable domain of the antibody of the present invention to form a chimeric bivalent antibody.

The aforementioned antibody may be a monovalent antibody. Methods for preparing monovalent antibodies are known in the art to which this invention pertains. For example, a method for recombinant expression of immunoglobulin light chains and modified heavy chains. The heavy chain is usually truncated at any position in the Fc region to prevent the heavy chains from cross-linking with each other. Alternatively, the relevant cysteine residues are substituted with other amino acid residues or deleted to prevent cross-linking.

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

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

Fully human and humanized antibodies

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

Typically, humanized antibodies contain one or more amino acid residues introduced from a non-human source. These non-human amino acid residues are often referred to as "import" residues and are usually derived from the "import" variable domain. According to some embodiments, humanization can be basically performed according to the following method of Winter and colleagues (Jones et al., Nature, 321: 522-525 (1986); Riechmann et al., Nature, 332: 323-327 ( 1988); Verhoeyen et al., Science, 239: 1534-1536 (1988)), by replacing the corresponding sequences of human antibodies with rodent CDRs or CDR sequences. Thus, this "humanized" antibody portion (U.S. Patent No. 4,816,567), which is essentially less than a fully human antibody, has its variable domains replaced by corresponding sequences from non-human sources. In practice, humanized antibody portions are typically human antibody portions in which some CDR residues and possibly some framework region residues are replaced with residues from similar positions in rodent antibodies.

An alternative approach to humanization of fully human antibody systems. For example, it is now possible to generate transgenic animals (e.g., mice) that are capable of producing a complete library of fully human antibodies upon immunization without producing endogenous immunoglobulins. For example, it has been reported that homozygous deletion of the antibody heavy chain junction region (JH) gene in chimeric and germline mutant mice completely inhibits endogenous antibody production. Transferring a human germline immunoglobulin gene array into this germline mutant mouse can produce human antibodies in response to antigen stimulation, see, e.g., akobovits et al., PNAS USA, 90:2551 (1993); Jakobovits et al ., Nature, 362:255-258 (1993); Bruggemann et al., Year in Immunol., 7:33 (1993); U.S. Patent Nos. 5,545,806, 5,569,825, 5,591,669, 5,545,807; and WO 97/17852. Alternatively, fully human antibodies can be produced by introducing human immunoglobulin loci into transgenic animals (eg, mice in which endogenous immunoglobulin genes have been partially or completely silenced). After antigen stimulation, it can be found that the production of fully human antibodies is very similar to its production in humans in all aspects, including genetic recombination, assembly and antibody libraries. This method is described in, for example, U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016, and Marks et al., Bio/Technology, 10: 779-783 (1992); Lonberg et al., Nature, 368: 8 56 -859 (1994); Morrison, Nature, 368: 812-813 (1994); Fishwild et al., Nature Biotechnology, 14: 845-851 (1996); Neuberger, Nature Biotechnology, 14: 826 (1996); Lonberg and Described in Huszar, Intern. Rev. Immunol., 13: 65-93 (1995).

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

Anti-FasL antibody variants

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

In some embodiments, anti-FasL antibody variants with one or more amino acid substitutions are provided. The target sites for substitution mutations include hypervariable regions (HVRs) and framework regions (FRs). Amino acid substitutions can be introduced into the antibody of interest and the products screened for desired activity, e.g., improved biological activity, maintained/improved antigen binding capacity, reduced immunogenicity, or improved ADCC or CDC.

Conservative substitutions are shown in Table 4 below.

Table 4 Conservative substitutions original residue Exemplary substitutions ideal replacement Ala (A) Val; Leu; Ile Val Arg(R) Lys; Gln; Asn Lys Asn(N) Gln; His; Asp, Lys; Arg gnc Asp(D) Glu; Asn Glu Cys(C) Ser; Ala Ser Gln(Q) Asn;Glu Asn Glu(E) Asp; Gln Asp Gly(G) Ala Ala His (H) Asn; Gln; Lys; Arg Arg Ile (I) Leu; Val; Met; Ala; Phe; Norleucine Leu Leu (L) Norleucine; Ile; Val; Met; Ala; Phe Ile Lys(K) Arg; Gln; Asn Arg Met(M) Leu; Phe; Ile Leu Phe (F) Trp; Leu; Val; Ile; Ala; Tyr Tyr Pro(P) Ala Ala Ser(S) Thr Thr Thr(T) Val; Ser Ser Trp(W) Tyr; Phe Tyr Tyr(Y) Trp; Phe; Thr; Ser Phe Val(V) Ile; Leu; Met; Phe; Ala; Norleucine Leu

Amino acids are divided into different categories based on the nature of their side chains: a. Hydrophobic amino acids: Norleucine, Met, Ala, Val, Leu, Ile; b. Neutral hydrophilic amino acids: cysteine Cys, serine Ser, threonine Thr, asparagine Asn, glutamate Gln; c. Acidic amino acids: aspartic acid Asp, glutamic acid Glu; d. Basic amino acids: Histidine His, Lysine Lys, Arginine Arg; e. Contains amino acids that affect chain direction: glycine Gly, proline Pro; f. Aromatic amino acids: tryptophan Trp, tyrosine Tyr, and phenylalanine Phe.

Substitution of non-conservative amino acids involves substitution of one category for another.

An exemplary substitution variant affinity matured antibody may be conveniently produced using, for example, phage display-based affinity maturation techniques. Briefly, one or more CDR residues are mutated, the variant antibody moieties are displayed on phage, and variants are screened for specific biological activities (e.g., activity to inhibit apoptosis or increased antibody affinity). Alterations (eg, substitutions) can be made in regions of HVRs to obtain improved antibody affinity or biological activity. Changes can occur in HVR "hot spots," codon-encoded residues that are subject to high mutation rates during somatic cell maturation (see, e.g., Chowdhury, Methods Mol. Biol. 207:179-196 (2008)). And/or detect the binding affinity of the resulting variants V _H and V _L at specific decisive residues (SDRs). Methods for constructing and reselecting affinity matured materials from secondary libraries have been described, for example, by Hoogenboom et al. in Methods in Molecular Biology 178:1-37 (O'Brien et al., ed., Human Press , Totowa, NJ, (2001)).

In partial affinity maturation embodiments, diversity is introduced into the variable genes selected for affinity maturation by any of a variety of methods (eg, error-prone PCR, strand shuffling, or oligonucleotide-directed mutagenesis). Next create a secondary library. The library is screened to identify antibody variants with the desired affinity. Another method of introducing diversity involves the HVR-mediated approach, in which several HVR residues (e.g., 4–6 residues at a time) are randomized. HVR residues for antigen binding are specifically identified, for example, using alanine scanning mutagenesis or modeling. Usually the CDR-H3 and CDR-L3 regions are particularly important targets.

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

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

Insertion of amino acid sequences, including fusions at the amino terminus and/or carboxyl terminus, ranging in length from 1 residue to polypeptides containing 100 or more residues, as well as insertion of 1 or more into the sequence amino acid residues. Examples of terminal insertions include antibodies with a methionine residue at the N-terminus. Other insertional variants of antibody molecules include fusion of an enzyme (e.g., ADEPT) or a peptide that increases the serum half-life of the antibody to the N- or C-terminus of the antibody molecule.

Fc region variants

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

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

In some embodiments, the invention also provides anti-FasL antibody variants (e.g., full-length anti-FasL antibody variants), which comprise an Fc region with some but not all effector functions, such that they have an extended half-life in vivo, but specific Effector functions (such as CDC or ADCC) are non-essential or deleterious, making anti-FasL antibodies ideal candidates for the present invention. Reduction/elimination of CDC and/or ADCC activity is confirmed by performing cytotoxicity assays in vitro and/or in vivo. For example, Fc receptor (FcR) binding assays are used to confirm that the antibody lacks FcγR binding ability (and therefore may lack ADCC activity) but still retains FcRn binding ability. Among the main cells that mediate ADCC, NK cells only express FcγRIII, while monocytes express FcγRI, FcγRII and FcγRIII. The expression of FcR on hematopoietic cells is summarized in Table 3 on page 464 of Ravetch and Kinet Annu. Rev. Immunol. 9:457-492 (1991). Non-limiting examples of in vitro assessment of ADCC activity of target molecules are described in U.S. Patent No. 5,500,362 (see, e.g., Hellstrom, I. et al. Proc. Nat'l Acad. Sci. USA 83:7059-7063 (1986) and Hellstrom, I et al., Proc. Nat'l Acad. Sci. USA 82:1499-1502 (1985); U.S. Patent No. 5,821,337 (see Bruggemann, M. et al., J. Exp. Med. 166: 1351-1361 (1987)). Alternatively, nonradioactive detection methods can be used (see, e.g., ACTI™ Flow Cytometry Nonradioactive Cytotoxicity Assay (CellTechnology, Inc. Mountain View, Calif.) and CYTOTOX 96™ Nonradioactive Cytotoxicity Test Assay (Promega, Madison, Wis.). The effector cells used in such assays include peripheral blood mononuclear cells (PBMC) and natural killer cells (NK). Alternatively, the ADCC activity of the target molecule is assayed in vivo , for example, in animal models, as described in Clynes et al. Proc. Nat'l Acad. Sci. USA 95:652-656 (1998). At the same time, a C1q binding assay can also be performed to confirm that the antibody cannot bind to C1q, There is thus a lack of CDC activity. See, eg, C1q and C3c binding ELISA in WO 2006/029879 and WO 2005/100402. To assess complement activation, CDC assays can be performed (see, eg, Gazzano-Santoro et al., J. Immunol. Methods 202:163 (1996); Cragg, M. S. et al., Blood 101:1045-1052 (2003); and Cragg, M. S. and M. J. Glennie, Blood 103:2738-2743 (2004)). The technical field to which this invention belongs has been established Known methods are used to determine FcRn binding and in vivo clearance/half-life (see, e.g., Petkova, S. B. et al., Int'l. Immunol. 18(12):1759-1769 (2006)).

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

Such antibody variants with increased or decreased binding to FcRs have been described (see, e.g., U.S. Patent No. 6,737,056; WO 2004/056312, and Shields et al., J. Biol. Chem. 9(2):6591-6604 (2001)).

In some embodiments, an anti-FasL antibody (eg, a full-length anti-FasL antibody) variant is provided, which includes an Fc region variant having one or more amino acid substitutions capable of enhancing the ADCC effect. In some embodiments, the Fc region variant contains one or more amine substitutions that can enhance the ADCC effect, and the positions of these substitutions are at positions 298, 333 and/or 334 (EU residue numbering) of the Fc region. In some embodiments, the aforementioned anti-FasL antibody (eg, full-length anti-FasL antibody) variant includes amino acid substitutions at positions S298A, E333A and K334A in the Fc region.

In some embodiments, changes in the Fc region result in changes (i.e., enhancement or attenuation) of C1q binding and/or complement-dependent cytotoxicity (CDC), see U.S. Patent No. 6,194,551, WO 99/51642, and Idusogie et al. ., J. Immunol. 164:4178-4184 (2000).

In some embodiments, an anti-FasL antibody (eg, a full-length anti-FasL antibody) variant is provided, which includes an Fc region variant with one or more amino acid substitutions that can extend the half-life or enhance interaction with the Fc receptor (FcRn ) combination. Antibodies with extended half-life and improved FcRn binding are described in US 2005/0014934A1 (Hinton et al.). The Fc region of these antibodies contains one or more amino acid substitutions that enhance the binding of the Fc region to FcRn. These Fc variants include 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424 in the Fc region Or one or more substitutions at residue 434, such as substitution at residue 434 in the Fc region (U.S. Patent No. 7,371,826).

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

The present invention contemplates anti-FasL antibodies (eg, full-length anti-FasL antibodies) comprising any one of the Fc variants described herein, or combinations thereof.

Glycosylation variants

In some embodiments, the anti-FasL antibody (eg, full-length anti-FasL antibody) provided in this specification is modified to increase or decrease the degree of glycosylation of the anti-NGF antibody. By changing the amino acid sequence of the anti-NGF antibody or its polypeptide part to add or remove one or multiple glycosylation sites, the addition or deletion of glycosylation sites on the anti-FasL antibody can be easily achieved.

The anti-FasL antibody contains an Fc region that can change the sugar attached to it. Natural antibodies produced by mammalian cells typically contain branched biantennary oligosaccharides linked to the CH2 domain Asn297 of the Fc region, usually via an N-link, see, e.g., Wright et al., TIBTECH 15:26-32 (1997 ). The aforementioned oligosaccharides can include a variety of sugars, such as mannose, N-acetyl glucoside (GlcNAc), galactose and sialic acid, as well as trehalose linked to GlcNAc in the "stem" part of the biantennary oligosaccharide structure. In some embodiments, the anti-FasL antibodies of the invention can be subjected to oligosaccharide modifications to produce anti-FasL antibody variants with certain improved properties.

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

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

In some embodiments, anti-FasL antibody (eg, full-length anti-FasL antibody) variants are provided that comprise an Fc region, wherein the carbohydrate structure linked to the Fc region has reduced fucose or lacks fucose, which may Enhance ADCC function. Specifically, the present specification provides anti-FasL antibodies that have reduced fucose relative to the same anti-FasL antibody produced by wild-type CHO cells. That is, they are characterized by having smaller amounts of fucose than antibodies produced by native CHO cells (e.g., CHO cells that produce native glycosylated forms, CHO cells that contain the native FUT8 gene). In some embodiments, the N-linked glycans of the aforementioned anti-FasL antibodies have less than 50%, 40%, 30%, 20%, 10%, or 5% fucose. For example, the fucose content of the anti-FasL antibody may be 1%-80%, 1%-65%, 5%-65%, or 20%-40%. In some embodiments, the N-linked glycan of the aforementioned anti-FasL antibody does not contain fucose, that is, the anti-FasL antibody does not contain fucose at all, or has no fucose or is defucosylated. The fucose content is calculated by calculating the average fucose content within the sugar chain attached to Asn297 relative to all sugar structures attached to Asn297 (such as complex, hybrid or mannose structures) measured by MALDI-TOF mass spectrometry. The total amount is determined as described in WO 2008/077546. Asn297 refers to the asparagine residue located at position 297 in the Fc region (EU Fc region residue numbering system). However, due to minor sequence changes in the antibody, Asn297 can also be located ±3 amino acids upstream or downstream of position 297, that is, between positions 294 and 300. These fucosylation variants may have enhanced ADCC function. See, for example, US Patent Publication Nos. US 2003/0157108 (Presta, L.), US 2004/0093621 (Kyowa Hakko Kogyo Co., Ltd). Examples of publications related to "afucosylated" or "fucose-deficient" antibody variants include, US 2003/0157108; WO 2000/61739; WO 2001/29246; US 2003/0115614; US 2002 /0164328; US 2004/0093621; US 2004/0132140; US 2004/0110704; US 2004/0110282; US 2004/0109865; WO 2003/085119; WO 2003/084570; WO 2005/03558 6;WO 2005/035778;WO 2005 /053742; WO 2002/031140; Okazaki et al. J. Mol. Biol. 336:1239-1249 (2004); Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004). Cell lines capable of producing afucosylated antibodies include Lec13 CHO cells lacking protein fucosylation function (Ripka et al. Arch. Biochem. Biophys. 249:533-545 (1986); US Pat Appl No US 2003/0157108 A1, Presta, L; and WO 2004/056312 A1, Adams et al., especially Example 11), and gene knockout cell lines, such as α-1,6-fucosyltransferase gene, FUT8 Gene-knocked-out CHO cells (see Yamane-Ohnuki et al. Biotech. Bioeng. 87:614 (2004); Kanda, Y. et al., Biotechnol. Bioeng., 94(4):680-688 (2006); and WO2003/085107).

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

In some embodiments, the aforementioned anti-FasL antibody (eg, full-length anti-FasL antibody) variant includes an Fc region capable of binding to FcγRIII. In some embodiments, a variant of the aforementioned anti-FasL antibody (e.g., a full-length anti-FasL antibody) comprising an Fc region has ADCC activity in the presence of human effector cells (e.g., T cells), or is the same as another having a human wild-type IgG1 Fc region. Anti-FasL antibodies (e.g., full-length anti-FasL antibodies) have enhanced ADCC activity in the presence of human effector cells.

Cysteine engineered variants

In some embodiments, it is desired to prepare a cysteine-engineered anti-FasL antibody (eg, a full-length anti-FasL antibody) in which one or more amino acid residues are replaced with cysteine residues. In some embodiments, the substitution residue occurs at an accessible site of the anti-FasL antibody. By replacing other residues with cysteine, reactive sulfhydryl groups are located in accessible sites of the anti-FasL antibody and can be used to couple the anti-FasL antibody to other moieties, such as drug moieties or linker-drugs. section to prepare anti-FasL immunoconjugates as further described herein. Cysteine-engineered anti-FasL antibodies (eg, full-length anti-FasL antibodies) can be prepared, for example, as described in U.S. Patent No. 7,521,541.

derivative

In some embodiments, the anti-FasL antibodies (eg, full-length anti-FasL antibodies) provided in this specification can be further modified to include other non-protein parts that are known and readily available in the technical field to which the invention belongs. Suitable moieties for derivatizing anti-FasL antibodies include, but are not limited to, water-soluble polymers. Non-limiting examples of water-soluble polymers include, but are not limited to, polyethylene glycol (PEG), ethylene glycol/propylene glycol copolymer, carboxymethylcellulose, dextran, polyvinyl alcohol, polyvinylpyrrolidone, Poly-1,3-dioxopentane, poly-1,3,6-trioxane, ethylene/maleic anhydride copolymer, polyamino acid (homopolymer or random copolymer), right Glycosanhydride or poly(n-vinylpyrrolidone) polyethylene glycol, propylene glycol homopolymer, propylene oxide/ethylene oxide copolymer, polyoxyethylated polyols (e.g. glycerol), polyvinyl alcohol and their mixture. Polyethylene glycol propionaldehyde offers advantages in manufacturing due to its stability in water. The polymers can be of any molecular weight and can be branched or unbranched. The number of polymers attached to the anti-FasL antibody can vary, and further if more than one polymer is attached, they can be the same or different molecules. Generally, the amount and/or type of polymer used for derivatization can be determined based on the following considerations, including but not limited to, the need to improve the properties or functions of the anti-FasL antibody, and whether the anti-FasL antibody derivative is used under specific conditions. treatment, etc.

pharmaceutical composition

This specification also provides compositions (such as pharmaceutical compositions) comprising any anti-FasL antibody (such as a full-length anti-FasL antibody), nucleic acid encoding an antibody, a vector comprising a nucleic acid encoding an antibody, or a host cell containing a nucleic acid or vector described in this specification. substances, also referred to as preparations here). In some embodiments, a pharmaceutical composition is provided, including any anti-FasL antibody described in this specification and a pharmaceutically acceptable carrier.

Suitable anti-FasL antibodies can be obtained by mixing anti-FasL antibodies of the desired purity with optional pharmaceutically acceptable carriers, excipients or stabilizers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)) FasL antibody preparation, prepared as a dry preparation or a liquid preparation. Acceptable carriers, excipients or stabilizers are non-toxic to the recipient at the dosage and concentration used and include buffers such as phosphates, citric acid and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (For example, octadecyldimethylbenzyl ammonium chloride; hexamethylammonium chloride; benzalkonium chloride; benzethonium chloride; phenol; butanol or benzyl alcohol; alkyl parahydroxybenzoates, such as p- Methyl parahydroxybenzoate or propyl parahydroxybenzoate; catechol; resorcinol; cyclohexanol; 3-pentanol and m-cresol); low molecular weight (less than 10 residues) peptides; proteins , such as serum albumin, gelatin or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine or ionine Amino acids; monosaccharides, disaccharides and other carbohydrates, including glucose, mannose or dextrin; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counterions such as sodium; Metal complexes (such as zinc-protein complexes); and/or non-ionic surfactants such as TWEEN™, PLURONICS™ or polyethylene glycol (PEG); exemplary formulations are as described in WO98/56418, and are expressly incorporated into this specification by reference. Dry formulations suitable for subcutaneous administration are described in WO97/04801. Such dry preparations can be reconstituted into high protein concentration preparations by using appropriate diluents, and the reconstituted preparations can be administered subcutaneously to the subject to be treated in this specification. Cationic liposomes or liposomes can be used to deliver the anti-FasL antibodies of the invention to cells.

In addition to anti-FasL antibodies (such as full-length anti-FasL antibodies), the preparations described in this specification may also contain one or more other active substances necessary for the treatment of specific diseases. Ideally, substances with complementary activities and no adverse reactions to each other. For example, in addition to the anti-FasL antibody, it may be desirable to further include antineoplastic agents, growth inhibitory agents, cytotoxic agents, or chemotherapeutic agents. Such molecules are present in combination in amounts effective for the intended purpose. Effective amounts of other substances will depend on the amount of anti-FasL antibody in the formulation, the type of disease or condition or treatment, and other factors as discussed above. These drugs are usually used at the same dosage and route of administration as described in this leaflet, or at 1% to 99% of the currently used dosage.

The aforementioned anti-FasL antibodies (e.g., full-length anti-FasL antibodies) can also be embedded in microcapsules prepared by, for example, coacervation technology and interfacial polymerization, such as in colloidal drug delivery systems (e.g., liposomes, albumin microspheres, microcapsules, etc.). Hydroxymethylcellulose or gelatin-microcapsules and poly(methyl methacrylate) microcapsules in emulsions, nanoparticles and nanocapsules) or in macroemulsions. Sustained release formulations can be prepared.

Sustained release formulations of anti-FasL antibodies (eg, full-length anti-FasL antibodies) can be prepared. Suitable examples of sustained release formulations include solid hydrophobic polymeric semipermeable matrices containing the antibodies (or fragments thereof) in the form of shaped articles, such as films or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (e.g., poly(2-hydroxyethyl methacrylate) or poly(vinyl alcohol)), polylactic acid (U.S. Patent No. 3,773,919), L-glutamic acid And L-ethyl glutamate copolymer, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymer such as LUPRON DEPOTTM (injectable composed of lactic acid-glycolic acid copolymer and leuprolide acetate) microspheres) and poly-D(-)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic-glycolic acid can release molecules over 100 days, some hydrogels can release proteins in much shorter periods of time. When encapsulated antibodies stay in the body for a long time, they will denature or aggregate due to exposure to a humid environment at 37°C, which may lead to loss of biological activity or changes in immunogenicity. Reasonable strategies can be designed to stabilize anti-FasL antibodies based on the corresponding mechanisms. For example, if the aggregation mechanism is found to be through thiodisulfide exchange to form intermolecular S-S bonds, this can be accomplished by modifying the sulfhydryl residues, drying in acidic solutions, controlling water content, using appropriate additives, and developing specific polymerization Material matrix composition to achieve stabilization.

In some embodiments, the aforementioned anti-FasL antibody (eg, full-length anti-FasL antibody) is formulated in a solution containing citrate, sodium chloride, acetate, succinate, glycine, polysorbate 80 (Tween 80) or the above in any combination of buffers.

Preparations for in vivo administration must be sterile. This can be easily accomplished, for example, by applying sterile filter membrane filtration.

Treatment using anti-FasL antibodies

Anti-FasL antibodies (e.g., full-length anti-FasL antibodies) and/or compositions of the invention can be administered to individuals (e.g., mammals, such as humans) to treat diseases caused by dysregulation of the FasL-Fas signaling pathway and/or Conditions (e.g., inflammatory diseases, autoimmune diseases, or cancer), including but not limited to pemphigus, transplant rejection, graft-versus-host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome , acute lung injury, acute respiratory distress syndrome, trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemic Reperfusion injury, diabetes, brain injury, spinal cord injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, Drug-induced liver injury/liver failure, autoimmune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the cancer is a FasL-positive cancer disease; in particular, a FasL-positive cancer disease is characterized by expression of FasL on the cell surface. In some embodiments, if at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, or at least 50% of the cells in the cancer sample exhibit FasL, the cancer can be considered FasL positive. In some embodiments, the number of FasL-positive cells can be detected by counting cells in microscopic sections. Therefore, in some embodiments, the present invention provides a method for treating diseases and/or conditions caused by dysregulation of the FasL signaling pathway (for example, inflammatory diseases, autoimmune diseases, or cancer), comprising administering to an individual an effective amount of A composition (for example, a pharmaceutical composition) of an anti-FasL antibody (for example, a full-length anti-FasL antibody), such as any anti-FasL antibody (for example, a full-length anti-FasL antibody) described in this specification. In some embodiments, The aforementioned individual system human beings.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising a FasL antibody (eg, a full-length anti-FasL antibody) that specifically binds to an epitope on human FasL, wherein the aforementioned epitope includes amino acid residues of human FasL. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease; in particular, a FasL-positive cancer disease is characterized by the expression of FasL on the cell surface. In some embodiments, if at least 1%, at least 2%, at least 5%, at least 10%, at least 20%, or at least 50% of the cells in the cancer sample exhibit FasL, cancer can be identified as FasL positive. In some embodiments, the number of FasL-positive cells can be detected by counting cells in microscopic sections. In some embodiments, the aforementioned individuals are humans.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 1, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 77, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 99 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 99 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 127 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 127 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 2, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 19, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 78, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 100 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 100 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 128 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 128 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 1, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 79, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 101 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 101 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 129 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 129 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 3, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 33, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 80, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 102 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 102 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 130 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 130 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 3, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 34, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 81, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 103 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 103 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 131 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 131 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 4, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 35, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 53, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 69, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 82, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 104 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 104 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 132 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 132 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 5, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 21, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 36, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 54, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 70, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 83, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 105 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 105 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 133 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 133 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 6, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 84, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 106 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 106 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 134 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 134 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 23, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 107 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 107 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 135 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 135 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 108 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 108 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 136 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 136 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 8, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 109 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 109 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 137 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 137 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 72, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 110 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 110 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 138 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 138 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 111 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 111 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 139 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 139 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 8, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 56, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 112 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 112 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 140 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 140 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 86, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 113 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 113 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 141 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 141 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 9, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 26, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 39, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 57, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 87, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 114 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 114 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 142 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 142 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 2, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 27, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 40, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 58, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 88, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 115 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 115 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 143 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 143 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 10, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 41, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 59, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 89, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 116 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 116 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 144 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 144 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 6, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 90, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 117 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 117 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 145 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 145 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 11, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 42, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 91, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 118 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 118 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 146 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 146 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 12, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 43, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 61, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 92, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 119 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 119 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 147 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 147 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 12, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 44, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 62, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 93, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 120 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 120 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 148 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 148 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 13, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 30, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 45, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 63, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 94, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 121 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 121 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 149 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 149 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 14, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 46, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 95, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 122 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 122 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 150 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 150 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 15, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 47, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 64, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 96, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 123 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 123 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 151 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 151 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain (V _H ), the aforementioned V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 16, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 31, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 48, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 65, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 76, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 97, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 124 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 124 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 152 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 152 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain ( _VH ), the aforementioned _VH comprising: HC-CDR1, comprising the amino acid sequence SEQ ID NO: 17, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 49, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 66, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 98, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 125 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 125 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 153 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 153 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

For example, in some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of A pharmaceutical composition comprising an anti-FasL antibody (e.g., a full-length anti-FasL antibody), a heavy chain variable domain ( _VH ), the aforementioned _VH comprising: HC-CDR1, comprising the amino acid sequence SEQ ID NO: 17, HC -CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 50, or a variant of the aforementioned V _H , whose HC-CDRs include up to about 5 Substitution of amino acids; and light chain variable domain (V _L ), the aforementioned V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 91, or a variant of the aforementioned V _L , whose LC-CDRs contain up to about 5 amino acid substitutions. In some embodiments, the aforementioned anti-FasL antibody system is a full-length antibody. In some embodiments, the aforementioned full-length anti-FasL antibody is an IgG1 or IgG4 antibody. In some embodiments, the aforementioned disease or disorder is selected from, for example, pemphigus, transplant rejection, graft versus host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute lung injury, acute respiratory distress syndrome , trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, diabetes, brain injury, spinal cord Injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury/liver failure, autologous Immune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. In some embodiments, the aforementioned cancer is a FasL-positive cancer disease. In some embodiments, the aforementioned individuals are humans.

In some embodiments, a method for treating an individual with a disease related to the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer) is provided, comprising administering to the individual an effective amount of an anti- The composition of a FasL antibody, wherein the aforementioned antibody includes: _VH , the aforementioned _VH includes the amino acid sequence shown in SEQ ID NO: 126 or a variant thereof, and the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 126 The sequence has at least about 80% sequence identity; and _VL , the aforementioned _VL includes the amino acid sequence shown in SEQ ID NO: 154 or a variant thereof, the aforementioned variant is the same as the amino acid sequence shown in SEQ ID NO: 154 The sequences have at least about 80% sequence identity.

In some embodiments, the anti-FasL antibody system described in this specification includes a full-length anti-FasL antibody of IgG1 or IgG4 constant region. In some embodiments, the aforementioned IgG1 is human IgG1. In some embodiments, the aforementioned IgG4 is human IgG4. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 155. In some embodiments, the heavy chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 156. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 157. In some embodiments, the light chain constant region comprises or consists of the amino acid sequence SEQ ID NO: 158.

In some embodiments, the aforementioned individuals are mammals (eg, humans, non-human primates, rats, mice, cattle, horses, pigs, sheep, goats, dogs, cats, etc.). In some embodiments, the aforementioned individuals are humans. In some embodiments, the aforementioned individual system clinical patients, clinical trial volunteers, experimental animals, etc. In some embodiments, the aforementioned individual is less than 60 years old (including, for example, less than 50, 40, 30, 25, 20, 15 or 10 years old). In some embodiments, the aforementioned individual is older than 60 years old (including, for example, older than 70, 80, 90 or 100 years old). In some embodiments, the aforementioned individuals are diagnosed with or are genetically susceptible to one or more diseases or conditions described herein (eg, inflammatory diseases, autoimmune diseases, or cancer). In some embodiments, the aforementioned individuals have one or more risk factors associated with one or more diseases or conditions described herein.

In some embodiments, the invention provides a method of delivering an anti-FasL antibody (such as any anti-FasL antibody described herein, such as an isolated anti-FasL antibody) to cells in an individual that express FasL on their surface, the method comprising The individual is administered a composition comprising an anti-FasL antibody.

Many diagnostic methods for inflammatory diseases, autoimmune diseases or cancer or any other disease exhibiting abnormal expression of FasL and the clinical description of such diseases are known in the art to which this invention belongs. Such methods include, but are not limited to, immunohistochemistry, PCR, and fluorescence in situ hybridization (FISH).

In some embodiments, the anti-FasL antibody (such as a full-length anti-FasL antibody) and/or composition of the present invention is combined with a second, third or fourth agent (including, for example, an immunosuppressant, an anti-inflammatory drug, an anti-tumor agent, growth inhibitors, cytotoxic agents, chemotherapeutic agents or vasostatic agents) to treat diseases related to the FasL-Fas signaling pathway.

Dosage and method of administration of anti-FasL antibodies

The dosage of an anti-FasL antibody (eg, isolated anti-FasL antibody) composition administered to an individual (eg, a human) may vary depending on the particular composition, the mode of administration, and the type of disease being treated. In some embodiments, the amount of the composition (eg, a composition comprising an anti-FasL antibody) is effective to produce an objective response (eg, a partial response or a complete response) in the treatment of an inflammatory disease, an autoimmune disease, or cancer. In some embodiments, the amount of the anti-FasL antibody composition is sufficient to produce a complete response in the subject. In some embodiments, the amount of anti-FasL antibody composition is sufficient to produce a partial response in an individual. In some embodiments, the anti-FasL antibody composition is administered at a dose (e.g., when administered alone) sufficient to produce greater than 20%, 25%, 30%, 35%, An overall response rate of 40%, 45%, 50%, 55%, 60%, 64%, 65%, 70%, 75%, 80%, 85%, or 90%.

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

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

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

In some embodiments, following the same administration method, the amount of the composition is close to the maximum tolerated dose (MTD) of the composition. In some embodiments, the amount of the composition is higher than 80%, 90%, 95% or 98% of the MTD.

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

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

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

Products and kits

In some embodiments of the present invention, an article is provided, the article comprising a substance that can be used to treat diseases related to the FasL-Fas signaling pathway (for example, inflammatory diseases, autoimmune diseases or cancer), or for delivering an anti-FasL antibody (eg, a full-length anti-FasL antibody) to cells expressing FasL on their surface. The aforementioned article of manufacture may comprise a container and a label or package insert on or accompanying the container. Suitable containers include, for example, bottles, vials, syringes, and the like. Containers can be made from a variety of materials, such as glass or plastic. Typically, the container contains a composition effective for treating the disease or condition described herein and has a sterile port (for example, the container may be an IV bag or a vial with a hypodermic needle-pierced cap) . At least one active substance in the composition is the anti-FasL antibody of the present invention. The label or package insert indicates the specific condition for which the composition is intended to be treated. The label or package insert further contains instructions for administering the anti-FasL antibody composition to a patient. Products and kits containing combination therapies are considered within the scope of this specification.

Package insert means the instructions usually included in the commercial packaging of a therapeutic product and containing information on the indications, usage, dosage, administration, contraindications and/or warnings relevant to the use of such therapeutic product. In some embodiments, the package insert indicates that the composition can be used to treat diseases related to the FasL-Fas signaling pathway (such as inflammatory diseases, autoimmune diseases, or cancer). In some embodiments, the package insert indicates that the composition can be used to treat the following diseases, including pemphigus, transplant rejection, graft-versus-host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, acute Lung injury, acute respiratory distress syndrome, trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia reperfusion Injury, diabetes, brain injury, spinal cord injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced Liver injury/liver failure, autoimmune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer.

In addition, the aforementioned article may also include a second container containing a pharmaceutically acceptable buffer, such as bacteriostatic water for injection (BWFI), phosphate buffer, Green's solution or glucose solution. Other materials required from a commercial and user perspective may also be included, including other buffers, diluents, filters, needles and syringes.

It also relates to kits that can be used for various purposes, such as for the treatment of diseases related to the FasL-Fas signaling pathway (such as inflammatory diseases, autoimmune diseases or cancer), or for the delivery of anti-FasL antibodies (such as full-length anti-FasL antibodies). FasL antibody) into cells expressing FasL on their surface, optionally in combination with an article of manufacture. The kit of the present invention contains one or a plurality of containers, which contains an anti-FasL antibody composition (or single-dose form and/or product). In addition, in some embodiments, it further contains another agent (such as the agent described in this specification). ) and/or instructions for use consistent with any method described in this manual. The kit may further include instructions for selecting individuals suitable for treatment. Instructions for use included in the kit of the present invention are usually written instructions on the label or package insert (such as a paper sheet included in the kit), machine-readable instructions (such as instructions on a magnetic or optical storage disc) It is also acceptable.

For example, in some embodiments, the kit includes a composition comprising an anti-FasL antibody (eg, a full-length anti-FasL antibody). In some embodiments, the kit includes: a) a composition comprising any anti-FasL antibody described in this specification, and b) at least one effective amount of other pharmaceutical agents that can enhance the effect of the anti-FasL antibody (such as the therapeutic effect , detection effect). In some embodiments, the kit includes: a) a composition comprising any anti-FasL antibody described herein, and b) administering the anti-FasL antibody composition to an individual for treating diseases related to the FasL-Fas signaling pathway (such as inflammatory diseases, autoimmune diseases, or cancer). In some embodiments, the kit includes: a) a composition comprising any anti-FasL antibody described in this specification, and b) at least one effective amount of other pharmaceutical agents that can enhance the effect of the anti-FasL antibody (such as the therapeutic effect , detection effect) and c) instructions for administering anti-FasL antibody compositions and other substances to individuals for the treatment of diseases related to the FasL-Fas signaling pathway (such as inflammatory diseases, autoimmune diseases, or cancer). The aforementioned anti-FasL antibodies and other substances may be present in separate containers or in the same container. For example, the kit may contain one specific composition or two or more compositions, one of which contains an anti-FasL antibody and the other of which contains another agent.

In some embodiments, the kit contains one (or a set of) nucleic acids encoding an anti-FasL antibody (eg, a full-length anti-FasL antibody). In some embodiments, the kit includes: a) a nucleic acid (or a set of nucleic acids) encoding an anti-FasL antibody (eg, a full-length anti-FasL antibody), and b) a host cell expressing the nucleic acid (or a set of nucleic acids). In some embodiments, the kit includes: a) a nucleic acid (or a set of) nucleic acids encoding an anti-FasL antibody (e.g., a full-length anti-FasL antibody), and b) instructions for use, suitable for: i) expressing the anti-FasL antibody in a host cell; FasL antibody, ii) preparing a composition comprising an anti-FasL antibody, and iii) administering a composition comprising an anti-FasL antibody to an individual to treat a disease associated with the FasL-Fas signaling pathway (e.g., inflammatory disease, autoimmune disease, or cancer). In some embodiments, the kit includes: a) a nucleic acid (or a set of nucleic acids) encoding an anti-FasL antibody (eg, a full-length anti-FasL antibody), b) a host cell expressing the nucleic acid (or a set of nucleic acids), and c ) instructions for use in: i) expressing an anti-FasL antibody in a host cell, ii) preparing a composition comprising an anti-FasL antibody, and iii) administering a composition comprising an anti-FasL antibody to an individual to treat a problem with the FasL-Fas signaling pathway Related diseases (such as inflammatory diseases, autoimmune diseases, or cancer).

The kit of the present invention is packaged in a suitable form. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (such as sealed mylar or plastic bags), etc. Kits can optionally provide other components such as buffers and instructions. Accordingly, the present invention also provides articles including vials, bottles, jars, flexible packaging (eg, sealed Mylar or plastic bags), and the like.

Instructions for use of anti-FasL antibody compositions usually include some information, such as dosage, administration period and route of administration, etc. Containers may be unit dose, bulk (eg, multi-dose packaging) or subunit dose. For example, a kit is provided that contains a sufficient dose of an anti-FasL antibody (eg, a full-length anti-FasL antibody) as described herein to effectively treat an individual for a long period of time, such as one week, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 2 weeks, 3 weeks, 4 weeks, 6 weeks, 8 weeks, 3 months, 4 months, 5 months, 7 months, 8 months, 9 months or more . The kit may also contain multiple unit doses of anti-FasL antibodies, pharmaceutical compositions and instructions for use, and be packaged in quantities sufficient for storage and use in pharmacies, such as hospital pharmacies and compounding pharmacies.

One of ordinary skill in the art to which this invention pertains will recognize that several embodiments are possible within the scope and spirit of this invention. The invention will now be described in more detail with reference to the following non-limiting examples. The following examples further illustrate the invention but should not be construed as limiting its scope in any way. [Example]

Example 1: Preparation of Antigen

Preparation of recombinant FasL/Fas protein

The cDNA (synthesized by Beijing Yiqiao Shenzhou Technology Co., Ltd.) encoding the extracellular region of human FasL (human FasL, hFasL; GenBank ID: 356) was constructed into a eukaryotic expression vector through sub-selection. A His tag and/or a human Fc tag and/or other tags commonly used by those skilled in the art of the present invention are added to the end of the cDNA encoding the above-mentioned protein to construct a plasmid containing the human or monkey FasL extracellular region coding sequence. The above plasmids are transfected into 293F cells for expression to produce fusion proteins containing the extracellular domain of FasL, such as His-hFasL and hFc-hFasL, where "His" represents the His tag and "hFc" represents the human Fc fragment.

Using the same method as above, construct a vector containing the coding sequence for the extracellular region of human Fas (human Fas, hFas; GenBank ID number: 355), and transfect 293F cells to express and produce a fusion protein containing the extracellular region of human Fas, such as His- hFas, where "His" represents the His tag.

According to the manufacturer's instructions, immobilized metal affinity chromatography (IMAC) was used to purify the recombinant protein with His tag using a nickel (Ni) column - HisCap Smart 6FF 5ml prepacked column (Changzhou Tiandi Renhe Biotechnology Co., Ltd., SA036C15). . The specific operation is as follows: First, use buffer A1 (50mM Na ₃ PO ₄ , 0.15M NaCl, pH 7.2) to balance the nickel column, with a flow rate of 150cm/h, and adjust the pH of the solution containing the fusion protein (such as the cell culture supernatant) to 7.2, load the sample at room temperature, and the flow rate is 150cm/h. Subsequently, the column was equilibrated again with 6 column volumes of A1 buffer at a flow rate of 150 cm/h. Finally, use 10 times the column volume of 50mM PB solution (containing 0.15M NaCl and 0.2M imidazole, pH 7.2) for elution, and collect the eluate. Use an ultrafiltration tube to ultrafiltrate the above solution into PBS and concentrate it to a certain concentration.

The fusion protein with Fc fragment was purified using Protein A column-MabCap At 4FF 5ml prepacked column (Changzhou Tiandi Renhe Biotechnology Co., Ltd., SA023C15). The specific operation is as follows: First, use 6 times the column volume of PBS buffer (including 50mM PBS and 0.15M NaCl, pH7.2) to equilibrate the protein A column, with a flow rate of 5ml/minute. The pH of the culture supernatant was adjusted to 7.2, and the sample was loaded at room temperature with a flow rate of 5 ml/min. Subsequently, the column was equilibrated again with 6-10 column volumes of PBS buffer at a flow rate of 5 ml/min. After complete equilibrium, add the eluate (including 0.1M Gly and 150mM NaCl, pH 3.2) for dissolution, and collect the eluate. Use an ultrafiltration tube to ultrafiltrate the above solution into PBS and concentrate it to a certain concentration.

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

Construct scFv antibody phage display library:

Mice were immunized using the human FasL extracellular domain as the antigen together with an equal volume (v/v) of adjuvant. The serum of mice after immunization was taken, and the total IgG titer in the serum of mice after immunization was detected by ELISA. After several rounds of immunization, mouse spleens were used to establish a phage display library. Briefly, the spleen of the immunized mouse was taken, RNA was extracted, cDNA was obtained through reverse transcription, V _H and V _K specific primers were used to amplify the V _H and V _K fragments, and after gel recovery and purification, the V _H and V fragments were connected. _K , construct scFv and select it into a phage display plasmid. Subsequently, the plastid is electroporated into E. coli TG1, and the phage is used to infect E. coli TG1 to obtain a scFv antibody phage display library.

Screening for anti-FasL single chain antibodies (scFv):

A scFv that specifically binds hFasL was isolated and obtained from a phage display library. Briefly, 2x10 ¹¹ PFU of the phage scFv library was added to the ELISA plate coated with His-hFasL antigen and cultured at 37°C for 2 hours. Wash 8-15 times with PBST solution (as the number of screening rounds increases, the number of washes increases). The phage bound to the hFasL antigen are captured by the FasL antigen coated on the ELISA plate, while the unbound phage are washed away. Use 0.1M Glycine-HCl solution (pH 2.2) to dissolve the phage that specifically binds to hFasL antigen. Infect TG1 cells in the exponential growth phase with the above phage, add ampicillin and culture for 1 hour, add helper phage, and culture overnight at 28°C and 220rpm shaker. The culture fluid was collected the next day, and the supernatant was obtained after centrifugation to enter the next round of screening. After multiple rounds of panning, a positive scFv antibody library was obtained.

ELISA method to detect anti-FasL single chain antibodies:

The enriched phages after panning were screened by ELISA. Briefly, His-hFasL antigen was dissolved in PBS solution, coated on a 96-well plate at 0.1 µg/well, and incubated at 4°C overnight. After washing once with PBST solution, 90 μL of PBS containing 4% skimmed milk powder was added to each well. Then add 10 μL of phage-scFv culture supernatant to the corresponding wells and incubate at 37°C for 1-2 hours. After washing 8 times with PBST solution, 100 μL/well of anti-M13-HRP antibody (Sino Biological, 11973-MM05T-H) diluted at 1:4000 was added. Incubate at 37°C for 1 hour. After washing the plate 6 times with PBST, add TMB chromogenic solution, 100 μL/well, and incubate at room temperature in the dark for 10 minutes. The color reaction was terminated with 2M H ₂ SO ₄ , and the absorbance value at 450 nm was read with a microdisk analyzer. At the end of the screening process, a series of positive scFv antibodies are obtained and sequenced.

Example 3: Preparation and characterization of full-length anti-FasL chimeric antibodies

3.1 Preparation of full-length anti-FasL chimeric antibodies

The obtained positive scFv antibodies were reconstituted into chimeric antibodies with human IgG1 or IgG4 heavy chain constant regions and human kappa (κ) light chain constant regions. V _L and V _H were amplified from the phage display vector and constructed into eukaryotic expression vectors pTTa1-L (containing human kappa constant region) and pTT5-H1 (containing human IgG1 heavy chain constant region) or pTTa1-H4 (containing human IgG4 heavy chain constant region). The plastid expressing the light chain and the plastid expressing the heavy chain were co-transfected into 293F cells, cultured at 37°C, 5% CO ₂ , and 120 rpm for 6 days, and the culture medium was purified using a Protein A affinity chromatography column. The antibody purification method was the same as that using the protein A column in Example 1. After ultrafiltration and concentration, the antibody concentration was determined and further biochemical and biological activity analysis was performed.

3.2 Determination of binding ability of anti-FasL antibodies

Anti-FasL antibody affinity

The constructed full-length anti-FasL chimeric antibody (reconstituted into human IgG4 form) was tested for binding to human FasL to reflect the binding activity of the anti-FasL antibody to human FasL antigen. Briefly, human hFc-hFasL antigen was dissolved in PBS solution, spread on a 96-well plate at 0.1µg/well, and incubated at 4°C overnight. Block with 5% milk at 37°C for 1 hour and wash 6 times with PBST solution. Each antibody sample was first diluted to 66.67nM and subsequently serially diluted in a 1:4 ratio. Add the serially diluted samples to a 96-well plate, 100 μL per well, and incubate at 37°C for 1 hour. Then wash 6 times with PBST solution. Add 100 µL of anti-human kappa-HRP (SouthernBiotech, E1920-MJ11B, 1:4000 dilution) to each well and incubate at 37°C for 1 hour. Wash 6 times with PBST solution. Add 100µL TMB to each well, incubate at 37°C for 10-20 minutes, and terminate the reaction with 2M H ₂ SO ₄ . Use a microdisk analyzer to read the absorbance value at 450 nm. A binding curve was generated by GraphPad Prism, and the EC ₅₀ value of each anti-FasL antibody was calculated.

The results are shown in Table 5. The screened anti-FasL chimeric antibodies FL-M04, FL-M06, FL-M07, FL-M09, FL-M13, FL-M27, FL-M37, FL-M39～FL-M46 , FL-M51, FL-M52, FL-M55, FL-M58, FL-M60~FL-M62, FL-M65, FL-M68, FL-M69, FL-M71, FL-M76, FL-M77 and humans FasL antigens all have good binding ability. The binding ability of the above anti-FasL antibody to human FasL is significantly better than that of the FasL antagonist APG101 (Fas fusion protein, Apogenix); it is also better than or equivalent to the control antibody MAB126-100 (commercial anti-FasL antibody, RD).

Table 5: Binding ability of anti-FasL chimeric antibodies to human FasL Antibody name EC ₅₀ (nM) Antibody name EC ₅₀ (nM) FL-M04 0.161 FL-M51 1.138 FL-M06 0.148 FL-M52 0.365 FL-M07 0.157 FL-M55 0.525 FL-M09 0.162 FL-M58 0.307 FL-M13 0.14 FL-M60 0.93 FL-M27 0.161 FL-M61 0.624 FL-M37 0.735 FL-M62 0.435 FL-M39 1.27 FL-M65 0.55 FL-M40 0.974 FL-M68 0.399 FL-M41 0.991 FL-M69 0.309 FL-M42 0.826 FL-M71 0.468 FL-M43 0.756 FL-M76 0.605 FL-M44 1.013 FL-M77 0.855 FL-M45 0.77 APG101 23.53 FL-M46 0.546 MAB126-100 0.948

Anti-FasL antibody neutralizes ligand binding to the receptor:

This experiment was used to characterize the ability of an anti-FasL chimeric antibody (reconstituted into a human IgG4 form) to neutralize the binding of the ligand FasL to its receptor Fas. Briefly, His-hFas prepared in Example 1 was coated on a 96-well plate at 0.1 μg/well and kept overnight at 4°C. After washing with PBST solution, add 100 μL of 2% milk to each well. Block for 1 hour at 37°C, then wash with PBST solution. Each anti-FasL antibody sample was diluted to 12.0 μg/ml, followed by serial dilutions in a 1:4 ratio. The hFc-hFasL antigen (1.25 ug/mL) prepared in Example 1 was mixed with each serially diluted anti-FasL antibody, and then premixed at 37°C for 30 minutes. Add the above antigen-antibody premix to a 96-well plate, 100 µL/well, and incubate at 37°C for 1 hour. Add 100 µL anti-human IgG1 Fc-AP antibody (SouthernBiotech, 9054-04, 1:3000) to each well and incubate at 37°C for 1 hour. After washing 6 times with PBST solution, add 100µL pNPP solution to each well and incubate at 37°C for 10-20 minutes. The absorbance value at 405 nm was read and a neutralization curve was generated using GraphPad Prism software.

The results show that, taking FL-M04, FL-M06, FL-M07, FL-M09, FL-M13, and FL-M27 as examples, the ability of the anti-FasL chimeric antibody to neutralize the binding of FasL to Fas is equivalent to that of the control antibody MAB126-100. (Results not shown).

3.3 Activity determination of anti-FasL antibodies

Anti-FasL antibody inhibits Jurkat cell apoptosis induced by FasL antigen:

When actinomycin D is added to inhibit cell division, exogenous FasL can activate the apoptosis signaling pathway and mediate cell apoptosis, and the amount of ATP in cells is directly proportional to the number of cells in the culture. Based on the above principles, the amount of ATP in cells can be used to reflect the level of cell apoptosis, and then determine the activity of anti-FasL chimeric antibodies (reconstituted into human IgG4 form) in inhibiting Jurkat cell apoptosis induced by FasL antigen.

Jurkat cells (purchased from Peking Union Medical College Cell Bank, 1101HUM-PUMC000075) in the logarithmic growth phase were seeded in a 96-well plate at 5 × 10 ⁴ cells/well. Each antibody sample was diluted to 6.667 nM and subsequently serially diluted in a 1:3 ratio. Add 50µL actinomycin D (Hanhui Pharmaceutical Co., Ltd., China National Drug Approval Number H20023504), 25µL hFc-FasL recombinant fusion protein and 25µL serially diluted anti-FasL antibody into a 96-well plate containing Jurkat cells, and add actinomycin D The final concentrations of hFc-FasL recombinant fusion protein were 32 ng/mL and 5 ng/mL respectively. Incubate at 37°C, 5% _CO2 for 24 hours. Use CellTiter-Glo® Luminescence Cell Viability Detection Kit (Promega, G7572) to detect the amount of ATP present. The amount of ATP present is directly proportional to the luminescence signal generated. That is, add CellTiter-Glo® reagent to the 96-well cell culture plate. , 50µL per well, mix and incubate at room temperature for 10 minutes. Read the fluorescence value using a microdisk analyzer. The curve was generated by GraphPad Prism software, and the IC ₅₀ value of each anti-FasL antibody was calculated.

The results are shown in Table 6. Anti-FasL chimeric antibodies FL-M04, FL-M06, FL-M07, FL-M09, FL-M13, FL-M27, FL-M37, FL-M39～FL-M46, FL- M51, FL-M52, FL-M55, FL-M58, FL-M60～FL-M62, FL-M65, FL-M68, FL-M69, FL-M71, FL-M76 and FL-M77 induced by FasL antigen Jurkat cell apoptosis has obvious inhibitory effect. The ability of the above anti-FasL antibody to inhibit FasL antigen-induced Jurkat cell apoptosis was significantly better than the control APG101, and was comparable to the control antibody 119-4A (anti-FasL antibody, Apogenix).

Table 6: Ability of anti-FasL chimeric antibodies to inhibit Jurkat cell apoptosis induced by FasL antigen Antibody name IC ₅₀ (nM) Antibody name IC ₅₀ (nM) FL-M04 0.037 FL-M51 0.014 FL-M06 0.086 FL-M52 0.027 FL-M07 0.046 FL-M55 0.021 FL-M09 0.071 FL-M58 0.029 FL-M13 0.053 FL-M60 0.014 FL-M27 0.064 FL-M61 0.015 FL-M37 0.017 FL-M62 0.020 FL-M39 0.016 FL-M65 0.032 FL-M40 0.015 FL-M68 0.017 FL-M41 0.016 FL-M69 0.029 FL-M42 0.017 FL-M71 0.022 FL-M43 0.019 FL-M76 0.019 FL-M44 0.014 FL-M77 0.020 FL-M45 0.018 APG101 >100 FL-M46 0.027 119-4A 0.033

Anti-FasL antibody inhibits FasL antigen-induced apoptosis of HepG2 cells:

The experimental principle is the same as above, using the amount of ATP in cells to reflect the level of cell apoptosis, and then determining the activity of anti-FasL chimeric antibodies (reconstituted into human IgG4 form) in inhibiting apoptosis of HepG2 cells induced by FasL antigen.

HepG2 cells in the logarithmic growth phase (purchased from the Peking Union Medical College Cell Bank, 1101HUM-PUMC000035) were seeded in a 96-well plate at 2 × 10 ⁴ cells/well. Each antibody sample was diluted to 6.667 nM and subsequently serially diluted in a 1:3 ratio. Add 50µL actinomycin D, 25µL hFc-FasL recombinant fusion protein and 25µL serially diluted anti-FasL antibody into a 96-well plate containing HepG2 cells, so that the final concentrations of actinomycin D and hFc-FasL recombinant fusion protein are 1µg respectively. /mL and 5 ng/mL. Incubate at 37°C, 5% _CO2 for 48 hours. CellTiter-Glo® Luminescence Cell Viability Assay Kit (Promega, G7572) was used to detect the amount of ATP present, and the amount of ATP present is directly proportional to the luminescence signal generated. That is, add CellTiter-Glo® reagent to the 96-well cell culture plate, 50 µL per well, mix and incubate at room temperature for 10 minutes. Read the fluorescence value using a microdisk analyzer. The curve was generated by GraphPad Prism software, and the IC ₅₀ value of each anti-FasL antibody was calculated.

The results are shown in Table 7. Anti-FasL chimeric antibodies FL-M04, FL-M06, FL-M07, FL-M09, FL-M13, FL-M27, FL-M37, FL-M39～FL-M46, FL- M51, FL-M52, FL-M55, FL-M58, FL-M60～FL-M62, FL-M65, FL-M68, FL-M69, FL-M71, FL-M76 and FL-M77 induced by FasL antigen HepG2 cell apoptosis has obvious inhibitory effect. The ability of the above-mentioned anti-FasL antibodies to inhibit the apoptosis of HepG2 cells induced by FasL antigen is significantly better than that of the control APG101; and among the above-mentioned anti-FasL antibodies, except for FL-M27, FL-M46, FL-M52, FL-M65 and the control antibody MAB126-100 Apart from being basically equivalent, the other antibodies were significantly better than the control antibody MAB126-100.

Table 7: Ability of anti-FasL chimeric antibodies to inhibit FasL antigen-induced apoptosis of HepG2 cells Antibody name IC ₅₀ (nM) Antibody name IC ₅₀ (nM) FL-M04 0.025 FL-M51 0.017 FL-M06 0.026 FL-M52 0.089 FL-M07 0.028 FL-M55 0.023 FL-M09 0.025 FL-M58 0.031 FL-M13 0.032 FL-M60 0.016 FL-M27 0.071 FL-M61 0.018 FL-M37 0.018 FL-M62 0.024 FL-M39 0.019 FL-M65 0.039 FL-M40 0.019 FL-M68 0.019 FL-M41 0.019 FL-M69 0.021 FL-M42 0.019 FL-M71 0.027 FL-M43 0.021 FL-M76 0.017 FL-M44 0.019 FL-M77 0.017 FL-M45 0.023 APG101 11.3 FL-M46 0.213 MAB126-100 0.099

Anti-FasL antibodies inhibit FasL antigen-induced activation of the NF-κB signaling pathway:

When actinomycin D is added to inhibit cell division, exogenous FasL can not only activate the apoptosis signaling pathway, but also activate the NF-κB signaling pathway. After using caspase inhibitors to block the apoptosis pathway, exogenous FasL can only induce the activation of the NF-κB signaling pathway. HepG2-Dual (InvivoGen, hepg2d-nfis) is a dual reporter cell line of NF-κB-SEAP and IRF-Lucia. After exogenous FasL induces the activation of the NF-κB pathway, it initiates the secretion of embryonic alkaline phosphatase (SEAP). Performance, which can be determined by QUANTI-Blue ^™ substrate conversion. Based on the above experimental principles, the activity of SEAP in HepG2-Dual was used to determine the activity of the anti-FasL chimeric antibody (reconstituted into human IgG4 form) in inhibiting the activation of the NF-κB signaling pathway induced by FasL antigen.

HepG2-Dual cells in the logarithmic growth phase were seeded in a 96-well plate at 1 × 10 ⁵ cells/well. Each antibody sample was diluted to 625 nM followed by serial dilutions. Add hFc-FasL (final concentration: 700ng/ml), actinomycin D, Caspase inhibitor Z-VAD-FMK (Beyotime, C1202-5mg) and serially diluted anti-FasL antibodies into 96 wells containing HepG2-Dual cells. Incubate in plate at 37°C, 5% _CO2 for 24 hours. Mix 40 μL of cell culture supernatant with 160 μL of preheated QUANTI-Blue ^TM (Invivogen) solution, incubate for 90 minutes, and read the absorbance value at 650 nm. A curve was generated using GraphPad Prism software, and the EC ₅₀ value of each anti-FasL antibody was calculated.

The results are shown in Table 8. Anti-FasL chimeric antibodies FL-M06, FL-M39～FL-M46, FL-M51, FL-M52, FL-M55, FL-M58, FL-M60～FL-M62, FL- M65, FL-M68, and FL-M69 all had significant inhibitory effects on the activation of the NF-κB signaling pathway induced by FasL antigen. Among the above anti-FasL antibodies, except FL-M55 which is basically equivalent to the control APG101, the other antibodies are significantly better than the control APG101.

Table 8: Ability of anti-FasL chimeric antibodies to inhibit FasL antigen-induced activation of NF-κB signaling pathway Antibody name EC ₅₀ (nM) Antibody name EC ₅₀ (nM) FL-M06 0.703 FL-M52 0.781 FL-M39 2.197 FL-M55 3.342 FL-M40 2.007 FL-M58 1.207 FL-M41 1.989 FL-M60 1.93 FL-M42 2.123 FL-M61 1.715 FL-M43 1.903 FL-M62 1.681 FL-M44 2.144 FL-M65 1.522 FL-M45 1.528 FL-M68 1.326 FL-M46 2.009 FL-M69 1.457 FL-M51 0.941 APG101 7.226

The present invention claims the priority of the Chinese patent application with application number 202210069822. incorporated into this manual.

The contents of the electronic sequence list (text name: sequencelist.xml, recording date: 2023.02.10, size: 149 KB) are incorporated into this specification by reference in their entirety.

TW202334235A_112102838_SEQL.xml

Claims (22)

An isolated antibody that specifically recognizes FasL, characterized in that the anti-FasL antibody includes: (i) _VH , the _VH includes the HC-CDR1 included in the _VH as shown in the amino acid sequence SEQ ID NO: 99, HC-CDR2 and HC-CDR3; and _VL , _{the VL} comprising LC-CDR1, LC-CDR2 and LC-CDR3 as shown in the amino acid sequence SEQ ID NO: 127; (ii) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in V _H as shown in the amino acid sequence SEQ ID NO: 100; and V _L , which includes the amino acid sequence SEQ ID NO: 128 _VL includes LC-CDR1, LC-CDR2 and LC-CDR3; (iii) _VH includes HC-CDR1, HC-CDR2 and _VH as shown in the amino acid sequence SEQ ID NO: 101 HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 129; (iv) _VH , which comprises an amino group such as V _H comprising the HC-CDR1, HC-CDR2 and HC-CDR3 of the acid sequence SEQ ID NO: 102; and V _L comprising the LC of the V _L shown as the amino acid sequence SEQ ID NO: 130 -CDR1, LC-CDR2 and LC-CDR3; (v) _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 103; and V _L , which includes LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL as shown in the amino acid sequence SEQ ID NO: 131; (vi) _VH , which includes the amino acid sequence SEQ ID NO: _VH represented by 104 includes HC-CDR1, HC-CDR2 and HC-CDR3; and _VL includes LC-CDR1, LC-CDR2 contained by _VL as shown in amino acid sequence SEQ ID NO: 132 and LC-CDR3; (vii) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 105; and _VL , which includes amines such as _VL shown in the amino acid sequence SEQ ID NO: 133 includes LC-CDR1, LC-CDR2 and LC-CDR3; (viii) _VH , which includes _VH shown in the amino acid sequence SEQ ID NO: 106 HC-CDR1, HC-CDR2 and HC-CDR3 comprised; and _VL comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 134; ( ix) _VH , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 107; and _VL , which comprises the amino acid sequence SEQ ID NO : LC-CDR1, LC-CDR2 and LC-CDR3 included in V _L shown in 135; (x) V _H including HC-CDR1 included in V _H shown in amino acid sequence SEQ ID NO: 108, HC-CDR2 and HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 136; (xi) _VH , which Comprising V _H comprising HC-CDR1, HC-CDR2 and HC-CDR3 as shown in the amino acid sequence SEQ ID NO: 109; and V _L comprising V as shown in the amino acid sequence SEQ ID NO: 137 _L contains LC-CDR1, LC-CDR2 and LC-CDR3; (xii) _VH , which contains _VH containing HC-CDR1, HC-CDR2 and HC- as shown in the amino acid sequence SEQ ID NO: 110 CDR3; and _VL , which includes LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 138; (xiii) _VH , which includes the amino acid sequence HC-CDR1, HC-CDR2 and HC-CDR3 included in V _H shown in SEQ ID NO: 111; and V _L including LC-CDR1 included in V _L shown in amino acid sequence SEQ ID NO: 139 , LC-CDR2 and LC-CDR3; (xiv) _VH , which contains HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 112; and _VL , It includes LC-CDR1, LC-CDR2 and LC-CDR3 contained in _VL as shown in the amino acid sequence SEQ ID NO: 140; (xv) _VH , which includes the amino acid sequence SEQ ID NO: 113 _VH is shown to include HC-CDR1, HC-CDR2 and HC-CDR3; and _VL includes LC-CDR1, LC-CDR2 and LC included in _VL as shown in the amino acid sequence SEQ ID NO: 141 -CDR3; (xvi) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 114; and _VL , which includes the amino acid LC-CDR1, LC-CDR2 and LC-CDR3 included in the V _L shown in the sequence SEQ ID NO: 142; (xvii) V _H , which includes the LC-CDR1, LC-CDR2 and LC-CDR3 included in the V _H shown in the amino acid sequence SEQ ID NO: 115 HC-CDR1, HC-CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 143; (xviii) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in _VH as shown in the amino acid sequence SEQ ID NO: 116; and _VL , which includes the amino acid sequence SEQ ID NO: 144 The _VL shown includes LC-CDR1, LC- _CDR2 and LC-CDR3; (xix) _VH , which includes the HC-CDR1, HC- CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 145; (xx) V _H comprising as _VH including the HC-CDR1, HC-CDR2 and HC-CDR3 of the amino acid sequence SEQ ID NO: 118; and _VL including the _VL including the amino acid sequence SEQ ID NO: 146 LC-CDR1, LC-CDR2 and LC-CDR3; (xxi) _VH comprising HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 119; and _VL , which includes LC-CDR1, LC-CDR2 and LC-CDR3 included in _VL as shown in the amino acid sequence SEQ ID NO: 147; (xxii) _VH , which includes the amino acid sequence SEQ ID The V _H shown in NO: 120 includes HC-CDR1, HC-CDR2 and HC-CDR3; and V _L includes the LC-CDR1, LC included in the V _L shown in the amino acid sequence SEQ ID NO: 148 -CDR2 and LC-CDR3; (xxiii) _VH , which comprises HC-CDR1, HC-CDR2 and HC-CDR3 comprised by _VH as shown in the amino acid sequence SEQ ID NO: 121; and _VL , which comprises _VL as shown in the amino acid sequence SEQ ID NO: 149 includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxiv) _VH includes as shown in the amino acid sequence SEQ ID NO: 122 _VH includes HC-CDR1, HC-CDR2 and HC-CDR3; and _VL includes _VL including LC-CDR1, LC-CDR2 and LC-CDR3 as shown in the amino acid sequence SEQ ID NO: 150 ; (xxv) _VH , which includes HC-CDR1, HC-CDR2 and HC-CDR3 contained in _VH as shown in the amino acid sequence SEQ ID NO: 123; and _VL , which includes the amino acid sequence SEQ _VL shown in ID NO: 151 includes LC-CDR1, LC-CDR2 and LC-CDR3; (xxvi) _VH , which includes HC- included in _VH shown in amino acid sequence SEQ ID NO: 124 CDR1, HC-CDR2 and HC-CDR3; and V _L comprising LC-CDR1, LC-CDR2 and LC-CDR3 comprised by V _L as shown in the amino acid sequence SEQ ID NO: 152; (xxvii) V _H , which includes HC-CDR1, HC-CDR2 and HC-CDR3 included in V _H as shown in the amino acid sequence SEQ ID NO: 125; and V _L , which includes the amino acid sequence SEQ ID NO: 153 _VL includes LC-CDR1, LC-CDR2 and LC-CDR3; or (xxviii) _VH includes HC-CDR1, HC-CDR2 included in _VH as shown in the amino acid sequence SEQ ID NO: 126 and HC-CDR3; and _VL , which comprises LC-CDR1, LC-CDR2 and LC-CDR3 comprised by _VL as shown in the amino acid sequence SEQ ID NO: 154. An isolated antibody that specifically recognizes FasL, characterized in that the antibody includes: (i) _VH , the _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes The amino acid sequence SEQ ID NO: 18, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and _VL , which _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51. LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 77; (ii) V _H , the V _H includes: HC-CDR1, It includes the amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 19, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 32; and _VL , which _VL includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 51, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO : 78; (iii) V _H , which V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 1, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 18, and HC-CDR3 , which includes the amino acid sequence SEQ ID NO: 32; and _VL , which _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 67, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 79; (iv) V _H , the V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, HC- CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 33; and _VL , which _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 80; (v) _VH , the _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 3, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 34; and _VL , the _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 52, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence Sequence SEQ ID NO: 81; (vi) V _H , which V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 4, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which comprises the amino acid sequence SEQ ID NO: 35; and _VL , which _VL comprises: LC-CDR1, which comprises the amino acid sequence SEQ ID NO: 53, LC-CDR2, which comprises an amine group Acid sequence SEQ ID NO: 69, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 82; (vii) V _H , the V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 5. HC-CDR2, which includes the amino acid sequence SEQ ID NO: 21, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 36; and V _L , which V _L includes: LC-CDR1, which includes The amino acid sequence SEQ ID NO: 54, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 70, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 83; (viii) V _H , which V _H includes: HC-CDR1, which contains the amino acid sequence SEQ ID NO: 6, HC-CDR2, which contains the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which contains the amino acid sequence SEQ ID NO : 37; and V _L , which V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which Comprising the amino acid sequence SEQ ID NO: 84; (ix) V _H , the V _H comprising: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC-CDR2, which comprises the amino acid sequence SEQ ID NO: 23, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and _VL , which _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, It includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (x) V _H , the V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 37; and _VL , the _VL includes: LC- CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (xi) _VH , the _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which includes the amino acid sequence Sequence SEQ ID NO: 38; and V _L comprising: LC- _CDR1 comprising the amino acid sequence SEQ ID NO: 55, LC-CDR2 comprising the amino acid sequence SEQ ID NO: 71, and LC -CDR3, which comprises the amino acid sequence SEQ ID NO: 85; (xii) _VH , which _VH comprises: HC-CDR1, which comprises the amino acid sequence SEQ ID NO: 7, HC-CDR2, which comprises an amine group Acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and _VL , which _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 72, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (xiii) _VH , the _VH includes: HC-CDR1, which includes The amino acid sequence SEQ ID NO: 7, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and V _L , the V _L Comprising: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 55, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 85. ; (xiv) _VH , the _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 8, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 25, and HC-CDR3, which Comprising the amino acid sequence SEQ ID NO: 38; and _VL , the _VL comprising: LC-CDR1, comprising the amino acid sequence SEQ ID NO: 56, LC-CDR2, comprising the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 85; (xv) V _H , which V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 7, HC-CDR2, It includes the amino acid sequence SEQ ID NO: 24, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 38; and _VL , the _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 86; (xvi) V _H , the V _H includes: HC- CDR1, which includes the amino acid sequence SEQ ID NO: 9, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 26, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 39; and V _L , the _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 57, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 87; (xvii) V _H , which V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 2, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 27, and HC -CDR3, which comprises the amino acid sequence SEQ ID NO: 40; and _VL , which _VL comprises: LC-CDR1, which comprises the amino acid sequence SEQ ID NO: 58, LC-CDR2, which comprises the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 88; (xviii) _VH , the _VH includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 10, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 20, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 41; and _VL , which _VL includes: LC-CDR1, which includes an amine group Acid sequence SEQ ID NO: 59, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 89; (xix) V _H , the V _H Comprising: HC-CDR1, which contains the amino acid sequence SEQ ID NO: 6, HC-CDR2, which contains the amino acid sequence SEQ ID NO: 22, and HC-CDR3, which contains the amino acid sequence SEQ ID NO: 37 ; and _VL , the _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 55, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 71, and LC-CDR3, which includes the amine The amino acid sequence SEQ ID NO: 90; (xx) V _H , the V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 11, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 42; and _VL , _which includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 60, LC-CDR2, which includes Amino acid sequence SEQ ID NO: 74, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 91; (xxi) V _H , the V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 43; and V _L , the V _L includes: LC-CDR1, It includes the amino acid sequence SEQ ID NO: 61, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 75, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 92; (xxii) V _H , the V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 12, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 29, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 44; and V _L comprising: LC-CDR1 comprising the amino acid sequence SEQ ID NO: 62, LC-CDR2 comprising _the amino acid sequence SEQ ID NO: 75, and LC-CDR3 _, which includes the amino acid sequence SEQ ID NO: 93; (xxiii) V _H , which includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 13, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 30, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 45; and _VL , which _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 63, LC- CDR2, which includes the amino acid sequence SEQ ID NO: 73, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 94; (xxiv) _VH , which includes: HC- _CDR1 , which includes an amine group Acid sequence SEQ ID NO: 14, HC-CDR2 comprising the amino acid sequence SEQ ID NO: 20, and HC-CDR3 comprising the amino acid sequence SEQ ID NO: 46; and _{V L comprising} : LC-CDR1, which includes the amino acid sequence SEQ ID NO: 51, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 95; ( xxv) V _H comprising: HC-CDR1 comprising the amino acid sequence SEQ ID NO: 15, HC-CDR2 comprising the amino _acid sequence SEQ ID NO: 20, and HC-CDR3 comprising the amine The amino acid sequence SEQ ID NO: 47; and _VL , the _VL includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 64, LC-CDR2, which includes the amino acid sequence SEQ ID NO: 68, and LC-CDR3, which includes the amino acid sequence _SEQ ID NO: 96; (xxvi) V _H , which includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 16, HC-CDR2, which includes The amino acid sequence SEQ ID NO: 31, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 48; and V _L , which V _L includes: LC-CDR1, which includes the amino acid sequence SEQ ID NO: 65. LC-CDR2, which includes the amino acid sequence SEQ ID NO: 76, and LC-CDR3, which includes the amino acid sequence SEQ ID NO: 97; (xxvii) V _H , the V _H includes: HC-CDR1, It includes the amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC-CDR3, which includes the amino acid sequence SEQ ID NO: 49; and _VL , which _VL includes: LC-CDR1, which contains the amino acid sequence SEQ ID NO: 66, LC-CDR2, which contains the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO : 98; or (xxviii) V _H , which V _H includes: HC-CDR1, which includes the amino acid sequence SEQ ID NO: 17, HC-CDR2, which includes the amino acid sequence SEQ ID NO: 28, and HC- CDR3, which comprises the amino acid sequence SEQ ID NO: 50; and _VL , which _VL comprises: LC-CDR1, which comprises the amino acid sequence SEQ ID NO: 60, LC-CDR2, which comprises the amino acid sequence SEQ ID NO: 74, and LC-CDR3, which contains the amino acid sequence SEQ ID NO: 91. The isolated antibody that specifically recognizes FasL as described in claim 1 or 2, wherein it includes: (i) _VH , which includes the amino acid sequence shown in SEQ ID NO: 99 or a variant thereof, which variant The body has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 99; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 127 or a variant thereof, which variant is identical to the amino acid sequence shown in SEQ ID NO: 127 The amino acid sequence shown in SEQ ID NO: 127 has at least about 80% sequence identity; (ii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 100 or a variant thereof, which variant is identical to The amino acid sequence shown in SEQ ID NO: 100 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 128 or a variant thereof, which variant is identical to SEQ ID The amino acid sequence shown in NO: 128 has at least about 80% sequence identity; (iii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 101 or a variant thereof, which variant is identical to SEQ ID The amino acid sequence shown in NO: 101 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 129 or a variant thereof, which variant is identical to SEQ ID NO: The amino acid sequence shown in SEQ ID NO: 129 has at least about 80% sequence identity; (iv) _VH , which includes the amino acid sequence shown in SEQ ID NO: 102 or a variant thereof, which variant is identical to SEQ ID NO: The amino acid sequence shown in 102 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 130 or a variant thereof, which variant is identical to the amino acid sequence shown in SEQ ID NO: 130 The amino acid sequence shown in SEQ ID NO: 103 has at least about 80% sequence identity; (v) _VH , which includes the amino acid sequence shown in SEQ ID NO: 103 or a variant thereof, which variant is identical to the amino acid sequence shown in SEQ ID NO: 103 The amino acid sequence shown has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 131 or a variant thereof, which variant is identical to the amino acid sequence shown in SEQ ID NO: 131 The amino acid sequence has at least about 80% sequence identity; (vi) _VH , which contains the amino acid sequence shown in SEQ ID NO: 104 or a variant thereof, which variant is identical to the amino acid sequence shown in SEQ ID NO: 104 The amino acid sequence has at least about 80% sequence identity; and V _L includes the amino acid sequence shown in SEQ ID NO: 132 or a variant thereof that is identical to the amino group shown in SEQ ID NO: 132 The acid sequence has at least about 80% sequence identity; (vii) _VH , which contains the amino acid sequence shown in SEQ ID NO: 105 or a variant thereof that is identical to the amino group shown in SEQ ID NO: 105 The acid sequence has at least about 80% sequence identity; and V _L comprises the amino acid sequence set forth in SEQ ID NO: 133 or a variant thereof that is identical to the amino acid sequence set forth in SEQ ID NO: 133 Having at least about 80% sequence identity; (viii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 106 or a variant thereof that is identical to the amino acid sequence shown in SEQ ID NO: 106 Have at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 134 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 134 Approximately 80% sequence identity; (ix) _VH , which includes the amino acid sequence shown in SEQ ID NO: 107 or a variant thereof, which has at least About 80% sequence identity; and V _L comprising the amino acid sequence shown in SEQ ID NO: 135 or a variant thereof that has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 135 % sequence identity; (x) _VH , which contains the amino acid sequence shown in SEQ ID NO: 108 or a variant thereof, which has at least about 80% similarity with the amino acid sequence shown in SEQ ID NO: 108 % sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 136 or a variant thereof that has at least about 80% sequence with the amino acid sequence shown in SEQ ID NO: 136 Identity; (xi) _VH , which includes the amino acid sequence shown in SEQ ID NO: 109 or a variant thereof, which variant has at least about 80% sequence with the amino acid sequence shown in SEQ ID NO: 109 Identity; and _VL , which comprises the amino acid sequence shown in SEQ ID NO: 137 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 137 ; (xii) _VH , which contains the amino acid sequence shown in SEQ ID NO: 110 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 110 ; And _VL , which comprises the amino acid sequence shown in SEQ ID NO: 138 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 138; ( xiii) _VH , which comprises the amino acid sequence shown in SEQ ID NO: 111 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 111; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 139 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 139; (xiv) _VH , which comprises the amino acid sequence shown in SEQ ID NO: 112 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 112; and _VL , which contains the amino acid sequence shown in SEQ ID NO: 140 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 140; (xv) V _H , which comprises the amino acid sequence shown in SEQ ID NO: 113 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 113; and _VL , which Comprising the amino acid sequence shown in SEQ ID NO: 141 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 141; (xvi) V _H , which Comprises the amino acid sequence shown in SEQ ID NO: 114 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 114; and _VL , which includes SEQ The amino acid sequence shown in ID NO: 142 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 142; (xvii) V _H , which includes SEQ The amino acid sequence shown in ID NO: 115 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 115; and _VL , which includes SEQ ID NO : The amino acid sequence shown in SEQ ID NO: 143 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 143; (xviii) V _H , which includes SEQ ID NO : The amino acid sequence shown in SEQ ID NO: 116 or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 116; and _VL , which includes SEQ ID NO: 144 The amino acid sequence shown or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 144; (xix) _VH , which includes SEQ ID NO: 117 The amino acid sequence shown or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 117; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 145 The amino acid sequence or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 145; (xx) _VH , which includes SEQ ID NO: 118 An amino acid sequence or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 118; and _VL , which contains the amine shown in SEQ ID NO: 146 A amino acid sequence or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 146; (xxi) _VH , which contains the amine shown in SEQ ID NO: 119 A amino acid sequence or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 119; and _VL , which includes the amino acid shown in SEQ ID NO: 147 Sequence or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 147; (xxii) _VH , which contains the amino acid shown in SEQ ID NO: 120 A sequence or a variant thereof, which variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 120; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 148 or Variants thereof, which have at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 148; (xxiii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 121 or A variant thereof, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 121; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 149 or a variant thereof A variant, which has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 149; (xxiv) _VH , which includes the amino acid sequence shown in SEQ ID NO: 122 or a variant thereof A variant having at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 122; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 150 or a variant thereof, This variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 150; (xxv) _VH , which includes the amino acid sequence shown in SEQ ID NO: 123 or a variant thereof, This variant has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 123; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 151 or a variant thereof, which variant The body has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 151; (xxvi) _VH , which includes the amino acid sequence shown in SEQ ID NO: 124 or a variant thereof, which variant The body has at least about 80% sequence identity with the amino acid sequence shown in SEQ ID NO: 124; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 152 or a variant thereof, which variant is identical to the amino acid sequence shown in SEQ ID NO: 152 The amino acid sequence shown in SEQ ID NO: 152 has at least about 80% sequence identity; (xxvii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 125 or a variant thereof, which variant is identical to The amino acid sequence shown in SEQ ID NO: 125 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 153 or a variant thereof, which variant is identical to SEQ ID The amino acid sequence shown in NO: 153 has at least about 80% sequence identity; or (xxviii) _VH , which includes the amino acid sequence shown in SEQ ID NO: 126 or a variant thereof, which variant is identical to SEQ The amino acid sequence shown in ID NO: 126 has at least about 80% sequence identity; and _VL , which includes the amino acid sequence shown in SEQ ID NO: 154 or a variant thereof, which variant is identical to SEQ ID NO : The amino acid sequence shown in 154 has at least about 80% sequence identity. The isolated antibody that specifically recognizes FasL according to any one of claims 1 to 3, wherein the antibody includes an Fc fragment. The isolated antibody that specifically recognizes FasL as described in claim 4, wherein the antibody is a full-length IgG antibody. The isolated antibody that specifically recognizes FasL as described in claim 5, wherein the antibody is a full-length IgG1, IgG2, IgG3 or IgG4 antibody. The isolated antibody that specifically recognizes FasL according to any one of claims 1 to 6, wherein the antibody is a chimeric, humanized or fully human antibody. The isolated antibody that specifically recognizes FasL as described in any one of claims 1 to 3, wherein the antibody is an antigen-binding fragment, and the antigen-binding fragment is selected from the group consisting of Fab, Fab', F(ab)' ₂ , Fab'-SH, single chain antibody (scFv), Fv fragment, dAb, Fd, nanobody, diabody and linear antibody. A nucleic acid molecule characterized by encoding an antibody specifically recognizing FasL as described in any one of claims 1 to 8. A vector comprising the nucleic acid molecule of claim 9. An isolated host cell, characterized by comprising the antibody specifically recognizing FasL according to any one of claims 1 to 8, the nucleic acid molecule according to claim 9, or the vector according to claim 10. A method for preparing an antibody that specifically recognizes FasL, the characteristics of which include: a) Cultivate the host cells as described in claim 11 under conditions that effectively express antibodies that specifically recognize FasL; and b) Obtain from the host cell the antibody expressed specifically recognizing FasL. A pharmaceutical composition characterized by comprising the antibody that specifically recognizes FasL as described in any one of claims 1 to 8, the nucleic acid molecule as described in claim 9, the vector as described in claim 10, and the vector as described in claim 11. The isolated host cells or the antibodies prepared by the method described in claim 12, and pharmaceutically acceptable carriers. The pharmaceutical composition according to claim 13, wherein the pharmaceutical composition further includes other pharmaceutical agents selected from the group consisting of immunosuppressive agents, anti-inflammatory drugs, anti-tumor agents, growth inhibitors, cytotoxic agents, chemotherapeutic agents or vascular agents. Inhibitors. An antibody according to any one of claims 1 to 8, the nucleic acid molecule according to claim 9, the vector according to claim 10, the isolated host cell according to claim 11, the nucleic acid molecule according to claim 12 The use of the antibody prepared by the method or the pharmaceutical composition described in any one of claims 13 to 14 in the preparation of drugs for treating, preventing and/or ameliorating diseases or conditions. A method of treating a disease or condition, characterized in that the method comprises administering to a desired individual an effective dose of the antibody of any one of claims 1 to 8, the nucleic acid molecule of claim 9, or the nucleic acid molecule of claim 10. The vector, the isolated host cell described in claim 11, the antibody prepared by the method described in claim 12, or the pharmaceutical composition described in any one of claims 13 to 14. The use described in claim 15 or the treatment method described in claim 16, wherein the disease or condition is an inflammatory disease, cancer or autoimmune disease related to the FasL-Fas signaling pathway. The use or treatment method as claimed in claim 17, wherein the disease or condition is selected from the group consisting of pemphigus, transplant rejection, graft-versus-host disease, systemic inflammatory response syndrome, sepsis, multiple organ dysfunction syndrome, and acute lung injury. , acute respiratory distress syndrome, trauma, multiple sclerosis, idiopathic pulmonary fibrosis, osteoarthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, myocardial infarction, cardiomyopathy, ischemia-reperfusion injury, Diabetes, brain injury, spinal cord injury, acute viral hepatitis B, acute viral hepatitis C, chronic hepatitis C, chronic hepatitis B, alcoholic hepatitis, non-alcoholic steatohepatitis, cirrhosis, drug-induced liver injury /Liver failure, autoimmune hepatitis, chronic kidney disease, acute kidney disease, diabetic kidney disease, cancer. The use or treatment method as claimed in claim 18, wherein the cancer is FasL positive cancer. The use as described in any one of claims 15, 17 to 19, wherein the drug is administered in combination with another pharmaceutical agent. The treatment method according to any one of claims 16 to 19, wherein the method further comprises administering another pharmaceutical agent to the desired individual. The use as claimed in claim 20 or the treatment method as claimed in claim 21, wherein the other agent is selected from the group consisting of immunosuppressive agents, anti-inflammatory agents, anti-tumor agents, growth inhibitors, cytotoxic agents, chemotherapeutic agents or vascular agents. Inhibitors​.