Anti-CD22 antibodies and uses thereof

Abstract

Aspects of the present application provide anti-CD22 antibodies and methods of using same in the treatment of subjects suffering from B cell disorders.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of and priority to U.S. Provisional Patent Application No. 63 / 488,161, filed March 2, 2023, U.S. Provisional Patent Application No. 63 / 488,166, filed March 2, 2023, U.S. Provisional Patent Application No. 63 / 460,851, filed April 20, 2023, U.S. Provisional Patent Application No. 63 / 460,852, filed April 20, 2023, and U.S. Provisional Patent Application No. 63 / 460,854, filed April 20, 2023, the contents of each of which are incorporated herein by reference in their entirety.

[0002] Sequence Listing The contents of the electronic sequence listing (183952035840SEQLIST.xml, size: 102,253 bytes and created on February 29, 2024) are incorporated herein by reference in their entirety. [Background technology]

[0003] CD22 is a cell surface sialoglycoprotein that is uniquely present on mature B lymphocytes rather than precursor B cells. CD22 regulates B cell function and proliferation. As B cells mature, expression increases and CD22 localization shifts to the cell surface. Other cells, such as lymphomas, leukemias, and lymphocytic B cells, also produce CD22. CD22 has been implicated in autoimmune disorders and B cell malignancies. Summary of the Invention [Means for solving the problem]

[0004] The present disclosure relates to, among other things, antibodies and antigen-binding fragments thereof that bind to CD22 (e.g., human CD22). For example, in one aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), the antibody or antigen-binding fragment thereof comprising an HC CDR3 comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:3. In some embodiments, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), the antibody or antigen-binding fragment thereof comprising an HC CDR3 comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:51. In some embodiments, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), the antibody or antigen-binding fragment thereof comprising an HC CDR3 comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:65. In some embodiments, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), wherein the antibody or antigen-binding fragment thereof comprises an HC CDR3 comprising or consisting of the amino acid sequence set forth in SEQ ID NO:79.

[0005] In another aspect, the disclosure features an isolated antibody, or antigen-binding fragment thereof, that binds to CD22 (e.g., human CD22), comprising an HC CDR3 that comprises or consists of an amino acid sequence that differs from SEQ ID NO: 3 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. In some embodiments, the disclosure features an isolated antibody, or antigen-binding fragment thereof, that binds to CD22 (e.g., human CD22), comprising an HC CDR3 that comprises or consists of an amino acid sequence that differs from SEQ ID NO: 51 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. In some embodiments, the disclosure features an isolated antibody, or antigen-binding fragment thereof, that binds to CD22 (e.g., human CD22), and comprises an HC CDR3 that comprises or consists of an amino acid sequence that differs from SEQ ID NO: 65 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. In some embodiments, the disclosure features an isolated antibody, or antigen-binding fragment thereof, that binds to CD22 (e.g., human CD22), and comprises an HC CDR3 that comprises or consists of an amino acid sequence that differs from SEQ ID NO: 79 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0006] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), wherein the antibody or antigen-binding fragment thereof has three CDRs (HC CDR1, HC CDR2, and HC CDR3) of a heavy chain variable region set forth in SEQ ID NO: 7. In some embodiments, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), wherein the antibody or antigen-binding fragment thereof has three CDRs (HC CDR1, HC CDR2, and HC CDR3) of a heavy chain variable region set forth in SEQ ID NO: 55. In some embodiments, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), wherein the antibody or antigen-binding fragment thereof has three CDRs (HC CDR1, HC CDR2, and HC CDR3) of a heavy chain variable region set forth in SEQ ID NO: 69. In some embodiments, the disclosure features an isolated antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), wherein the antibody or antigen-binding fragment thereof has three CDRs (HC CDR1, HC CDR2, and HC CDR3) of the heavy chain variable region set forth in SEQ ID NO: 83. In some embodiments, the CDRs are defined according to Kabat. In some embodiments, the CDRs are defined according to Chothia. In some embodiments, the CDRs are defined according to IMGT.

[0007] In another aspect, the disclosure features an antibody or antigen-binding fragment thereof that cross-competes with the binding of an antibody or antigen-binding fragment thereof comprising: (i) the amino acid sequence set forth in SEQ ID NO:7 and the amino acid sequence set forth in SEQ ID NO:8; (ii) the amino acid sequence set forth in SEQ ID NO:55 and the amino acid sequence set forth in SEQ ID NO:56; (iii) the amino acid sequence set forth in SEQ ID NO:69 and the amino acid sequence set forth in SEQ ID NO:70; or (iv) the amino acid sequence set forth in SEQ ID NO:83 and the amino acid sequence set forth in SEQ ID NO:84.

[0008] In another aspect, the disclosure features an antibody or antigen-binding fragment thereof that cross-competes with the binding of an antibody or antigen-binding fragment thereof comprising: (i) a heavy chain variable region comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:7 and a light chain variable region comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:8; (ii) a heavy chain variable region comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:55 and a light chain variable region comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:56; (iii) a heavy chain variable region comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:69 and a light chain variable region comprising, or consisting of the amino acid sequence set forth in SEQ ID NO:70; or (iv) a heavy chain variable region comprising, or consisting of, the amino acid sequence set forth in SEQ ID NO:83 and a light chain variable region comprising, or consisting of the amino acid sequence set forth in SEQ ID NO:84.

[0009] In some embodiments, any antibody or antigen-binding fragment thereof described herein comprises the three CDRs of the light chain variable region set forth in SEQ ID NO: 8 (LC CDR1, LC CDR2, and LC CDR3). In some embodiments, any antibody or antigen-binding fragment thereof described herein comprises the three CDRs of the light chain variable region set forth in SEQ ID NO: 56 (LC CDR1, LC CDR2, and LC CDR3). In some embodiments, any antibody or antigen-binding fragment thereof described herein comprises the three CDRs of the light chain variable region set forth in SEQ ID NO: 70 (LC CDR1, LC CDR2, and LC CDR3). In some embodiments, any antibody or antigen-binding fragment thereof described herein comprises the three CDRs of the light chain variable region set forth in SEQ ID NO: 84 (LC CDR1, LC CDR2, and LC CDR3). In some embodiments, the CDRs are defined according to Chothia. In some embodiments, the CDRs are defined according to IMGT.

[0010] In another aspect, the disclosure provides a HC CDR3 comprising: (i) (a) an HC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 1 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 2; and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 3; (ii) (a) an HC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 49 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 50; and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 51; (iii) (a) an HC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 64, and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 65; or (iv) an isolated antibody or antigen-binding fragment thereof comprising: (a) an HC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 78; and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 79.

[0011] In another aspect, the disclosure provides a HC CDR3 comprising: (i) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 1; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 2; and (c) an HC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 3 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (ii) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 49; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 50; and (c) an HC CDR3 that is or comprises the amino acid sequence that differs from SEQ ID NO: 51 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (iii) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 63; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 64; or (iv) an isolated antibody or antigen-binding fragment thereof comprising (a) an HC CDR1 which is or comprises the amino acid sequence set forth in SEQ ID NO: 63, (b) an HC CDR2 which is or comprises the amino acid sequence set forth in SEQ ID NO: 78, and (c) an HC CDR3 which is or comprises the amino acid sequence set forth in SEQ ID NO: 79 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0012] In another aspect, the disclosure provides a HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 1 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 2 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 3 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; CDR1, (b) an HC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 50 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 51 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (iii) (a) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, CDR2, and (c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 65 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; or (iv)(a) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.(b) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 78 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 79 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0013] In another aspect, the disclosure provides an LC CDR3 comprising: (i) (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 4 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 5; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 6; (ii) (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 52 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 53; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 54; (iii) (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 66 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 67; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 68; or (iv) an isolated antibody or antigen-binding fragment thereof comprising: (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 80 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 81; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 82.

[0014] In another aspect, the disclosure provides an LC CDR1 comprising: (i) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 4; (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 5 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 6; (ii) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 52; (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 53 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 54; (b) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 67 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 68; or (iv) an isolated antibody or antigen-binding fragment thereof comprising: (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 80; (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 81 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 82.

[0015] In another aspect, the disclosure provides a LC CDR3 comprising: (i) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 4; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 5; and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 6 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (ii) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 52; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 53; and (c) an LC CDR3 that is or comprises the amino acid sequence that differs from SEQ ID NO: 54 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (iii) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 66; and (b) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 67. or (iv) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 80, (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 81, and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 82 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0016] In another aspect, the disclosure provides an LC CDR comprising: (i) (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 4 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 5 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 6 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 53 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 54 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (iii) (a) an LC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 66 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; CDR2, and (c) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 68 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; or (iv)(a) an LC that is or includes an amino acid sequence that differs from SEQ ID NO: 80 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.The present invention features an isolated antibody or antigen-binding fragment thereof comprising: (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 81 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 81 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0017] In yet another aspect, the disclosure provides a HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 1 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 2 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 3 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (d) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 4 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. CDR1, (e) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 5 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (f) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 6 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (ii) (a) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 49 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 50 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. (c) an HC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 51 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (d) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 52 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions;CDR1, (e) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 53 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (f) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 54 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (iii) (a) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 64 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. (c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 65 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (d) an LC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 66 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (e) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 67 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (f) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 68 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. CDR3, or (iv) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; CDR1, (b) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 78 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions;(c) an HC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 79 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (d) an LC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 80 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (c) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 81 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (f) an LC CDR3 that is or includes an amino acid sequence that differs from SEQ ID NO: 82 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0018] In some embodiments, the antibodies or antigen-binding fragments thereof described herein comprise a heavy chain variable region sequence set forth in SEQ ID NO: 7, 55, 69, or 83.

[0019] In some embodiments, the antibodies or antigen-binding fragments thereof described herein comprise a light chain variable region sequence set forth in SEQ ID NO: 8, 56, 70, or 84.

[0020] In yet another aspect, the disclosure provides an antibody or antigen-binding fragment thereof that binds to CD22 (e.g., human CD22), comprising: (i) three CDRs of a heavy chain variable region set forth in SEQ ID NO: 7 (HC CDR1, HC CDR2, and HC CDR3) and three CDRs of a light chain variable region set forth in SEQ ID NO: 8 (LC CDR1, LC CDR2, and LC CDR3); (ii) three CDRs of a heavy chain variable region set forth in SEQ ID NO: 55 (HC CDR1, HC CDR2, and HC CDR3) and three CDRs of a light chain variable region set forth in SEQ ID NO: 56; (iii) three CDRs of a heavy chain variable region set forth in SEQ ID NO: 69 (HC CDR1, HC CDR2, and HC CDR3) and three CDRs of a light chain variable region set forth in SEQ ID NO: 70; or (iv) three CDRs of a heavy chain variable region set forth in SEQ ID NO: 83 (HC CDR1, HC CDR2, and HC CDR3). In some embodiments, the invention features an antibody or antigen-binding fragment thereof comprising three CDRs of a light chain variable region (LC CDR1, LC CDR2, and LC CDR3) set forth in SEQ ID NO: 84. In some embodiments, the CDRs are defined according to Kabat. In some embodiments, the CDRs are defined according to Chothia. In some embodiments, the CDRs are defined according to IMGT.

[0021] In some embodiments, the isolated antibody or antigen-binding fragment thereof described herein comprises: (i) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 1, (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 2, and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 3; (ii) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 49, (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 50, and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 51; (iii) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 63, (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 64, and (c) an HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 65; or (iv) (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 63, (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 78. and (c) a HC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO:79.

[0022] In some embodiments, the isolated antibody or antigen-binding fragment thereof described herein is selected from the group consisting of: (i) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 4, (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 5, and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 6; (ii) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 52, (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 53, and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 54; (iii) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 66, (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 67, and (c) an LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO: 68; or (iv) (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 80, (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 81. and (c) a LC CDR3 that is or comprises the amino acid sequence set forth in SEQ ID NO:82.

[0023] In some embodiments, the isolated antibody or antigen-binding fragment thereof described herein comprises: (i) (a) an HC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 1, (b) an HC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 2, (c) an HC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 3, (d) an LC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 4, (e) an LC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 5, and (f) an LC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6; (ii) (a) an HC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 49, (b) an HC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 50, (c) an HC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 51, (d) an LC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 52, (e) an LC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 53, and (f) an LC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 54; (iii) (a) an HC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 63, (b) an HC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 64. (c) HC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 65, (d) LC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 66, (e) LC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 67, and (f) LC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 68, or (iv) (a) HC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 63, (b) HC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 78, (c) HC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 79, (d) LC CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 80, (e) LC CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 81, and (f) LC CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 82.

[0024] In some embodiments, the isolated antibody or antigen-binding fragment thereof comprises (i) the heavy chain variable region sequence set forth in SEQ ID NO:7 and / or the light chain variable region sequence set forth in SEQ ID NO:8, (ii) the heavy chain variable region sequence set forth in SEQ ID NO:55 and / or the light chain variable region sequence set forth in SEQ ID NO:56, (iii) the heavy chain variable region sequence set forth in SEQ ID NO:69 and / or the light chain variable region sequence set forth in SEQ ID NO:70, or (iv) the heavy chain variable region sequence set forth in SEQ ID NO:83 and / or the light chain variable region sequence set forth in SEQ ID NO:84.

[0025] In some embodiments, the isolated antibody or antigen-binding fragment thereof comprises a heavy chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 7, 55, 69 or 83. Thus, for example, in some embodiments, the antibody or antigen-binding fragment thereof described herein comprises (i) (a) an HC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 1 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) an HC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 2 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (c) an HC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 3 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. a heavy chain variable region comprising a CDR3, the heavy chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 7; (ii) (a) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 49 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 50 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 51 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.a heavy chain variable region comprising a CDR3, the heavy chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 55; (iii) (a) an HC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 64 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an HC that is or includes an amino acid sequence that differs from SEQ ID NO: 65 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. a heavy chain variable region comprising a CDR3, the heavy chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 69; or (iv) (a) an HC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 63 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an HC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 78 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an HC that is or comprises an amino acid sequence that differs from SEQ ID NO: 79 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. The heavy chain variable region may comprise a heavy chain variable region comprising a CDR3, the heavy chain variable region comprising an amino acid sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 83.

[0026] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a heavy chain variable region comprising: (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 1; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 2; and (c) an HC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 3 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 7.

[0027] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a heavy chain variable region comprising: (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO:49; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO:50; and (c) an HC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO:51 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO:55.

[0028] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a heavy chain variable region comprising: (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 63; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 64; and (c) an HC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 65 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 69.

[0029] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a heavy chain variable region comprising: (a) an HC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 63; (b) an HC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 78; and (c) an HC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 79 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 83.

[0030] In some embodiments, the isolated antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 8, 56, 70, or 84. Thus, for example, in some embodiments, the antibodies or antigen-binding fragments thereof described herein comprise (i) (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 4 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 5 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 6 by no more than four (e.g., no more than three, no more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. (ii) a light chain variable region comprising a CDR3, the light chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 8; (ii) (a) an LC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 52 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 53 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 54 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.(iii) a light chain variable region comprising a CDR3, the light chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 56; (iii) (a) an LC CDR1 that is or includes an amino acid sequence that differs from SEQ ID NO: 66 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 67 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR2 that is or includes an amino acid sequence that differs from SEQ ID NO: 68 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. a light chain variable region comprising a CDR3, the light chain variable region comprising an amino acid sequence at least 75% (e.g., 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 70; or (iv) (a) an LC CDR1 that is or comprises an amino acid sequence that differs from SEQ ID NO: 80 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (b) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 81 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; and (c) an LC CDR2 that is or comprises an amino acid sequence that differs from SEQ ID NO: 82 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions. The light chain variable region may comprise a light chain variable region comprising a CDR3, the light chain variable region comprising an amino acid sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 84.

[0031] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a light chain variable region comprising: (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO:4; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO:5; and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO:6 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO:8.

[0032] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a light chain variable region comprising: (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 52; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 53; and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 54 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, wherein the light chain variable region comprises an amino acid sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 56.

[0033] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a light chain variable region comprising: (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 66; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 67; and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 68 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, wherein the light chain variable region comprises an amino acid sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 70.

[0034] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein may comprise a light chain variable region comprising: (a) an LC CDR1 that is or comprises the amino acid sequence set forth in SEQ ID NO: 80; (b) an LC CDR2 that is or comprises the amino acid sequence set forth in SEQ ID NO: 81; and (c) an LC CDR3 that is or comprises an amino acid sequence that differs from SEQ ID NO: 82 by four or fewer (e.g., three or fewer, two or fewer, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and that is at least 75% (e.g., 80%, 85%, 90%, 95%, 99% or 100%) identical to the amino acid sequence of SEQ ID NO: 84.

[0035] In some embodiments, the anti-CD22 antibody comprises an HC CDR1, an HC CDR2, an HC CDR3, an LC CDR1, an LC CDR2, and an LC CDR3, wherein (i) (a) the HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 1; (b) the HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 2; and (c) the HC (d) LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 4; (e) LC (f) LC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 5; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 6; or (ii)(a)HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:49, and (b) HC CDR2 comprises at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:50.(c) the HC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 51; (d) the LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 52; and (e) the LC (f) LC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 53; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 54; or (iii)(a)HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; (b) HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 64; and (c) HC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:65, and (d) LC CDR1 comprises at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:66.(e) LC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 67; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 68; or (iv)(a)HC (b) HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; (b) HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 78; and (c) HC (d) LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 80; (e) LC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 81, and (f) LC CDR3 comprises at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 82.Contains amino acid sequences with 99% or 100% identity.

[0036] In some embodiments, the anti-CD22 antibody comprises (i) (a) a HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99%, or 100% identity to SEQ ID NO: 1; and (b) a HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99%, or 100% identity to SEQ ID NO:2. and (c) a heavy chain variable domain (V CDR2) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:3. H ), and (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:4; and (e) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:5. and (f) a light chain variable domain (V CDR2) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:6. L), (ii) (a) an HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 49; and (b) an HC comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 50. and (c) a heavy chain variable domain (VH) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 51. H ), and (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 52; and (e) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 53. and (f) a light chain variable domain (V CDR2) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 54. L), (iii) (a) a HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; and (b) a HC comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 64. and (c) a heavy chain variable domain (VH) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 65. H ), and (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 66; and (e) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 67. and (f) a light chain variable domain (V CDR2) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 68. L), or (iv) (a) a HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; and (b) a HC comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 78. and (c) a heavy chain variable domain (VH) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 79. H ), and (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 80; and (e) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 81. and (f) a light chain variable domain (V CDR2) comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 82. L ) is included.

[0037] In some embodiments, the anti-CD22 antibody comprises a V molecule comprising at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c). H(i) (d) to (f), (ii) (d) to (f), (iii) (d) to (f), or (iv) (d) to (f), L or (i) (a) to (c), (ii) (a) to (c), (iii) (a) to (c), or (iv) (a) to (c), comprising at least two CDRs selected from H and V comprising at least two CDRs selected from (i) (d) to (f), (ii) (d) to (f), (iii) (d) to (f), or (iv) (d) to (f). L Includes:

[0038] In some aspects, the present disclosure provides antibodies comprising: (i) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the antibodies listed in Table 1; (ii) the VH and / or VL of any one of the antibodies listed in Table 1; or (iii) the heavy chain and / or light chain of any one of the antibodies listed in Table 1.

[0039] In some embodiments, the antibody comprises (i) a heavy chain comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 11 and an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 12. (ii) a light chain comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 57, and an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 58. (iii) a heavy chain comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 71 and a light chain comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 72. or (iv) a heavy chain comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 85 and a light chain comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 86.In some embodiments, the antibody comprises (i) a heavy chain set forth in SEQ ID NO: 11 and a light chain set forth in SEQ ID NO: 12, (ii) a heavy chain set forth in SEQ ID NO: 57 and a light chain set forth in SEQ ID NO: 58, (iii) a heavy chain set forth in SEQ ID NO: 71 and a light chain set forth in SEQ ID NO: 72, or (iv) a heavy chain set forth in SEQ ID NO: 85 and a light chain set forth in SEQ ID NO: 86.

[0040] In some aspects, the disclosure provides antibodies comprising a HC CDR3 comprising the amino acid sequence of ARELTGDAFDX7 (SEQ ID NO: 35), where X7 is I or L.

[0041] In some embodiments, the antibody further comprises an HC CDR1 comprising the amino acid sequence of GFX1FX2X3YG (SEQ ID NO: 33) (wherein X1 is T or I, X2 is S or R, and X3 is S or N) and / or an HC CDR2 comprising the amino acid sequence of IYYDGX4X5X6 (SEQ ID NO: 34) (wherein X4 is N or S, X5 is K or N, and X6 is K or N).

[0042] In some embodiments, the antibody comprises an LC CDR1 comprising the amino acid sequence of QX8IGSX9 (SEQ ID NO: 36) (wherein X8 is S or R and X9 is S or H), an LC CDR2 comprising the amino acid sequence of YAS, and / or an LC CDR3 comprising the amino acid sequence of HQSSX 10 EPYT (SEQ ID NO: 38) (wherein X 10 is T, R, or S).

[0043] In some embodiments, the disclosure provides a HC CDR1 comprising the amino acid sequence of GFX1FX2X3YG (SEQ ID NO: 33) (wherein X1 is T or I, X2 is S or R, and X3 is S or N), a HC CDR2 comprising the amino acid sequence of IYYDGX4X5X6 (SEQ ID NO: 34) (wherein X4 is N or S, X5 is K or N, and X6 is K or N), a HC CDR3 comprising the amino acid sequence of ARELTGDAFDX7 (SEQ ID NO: 35) (wherein X7 is I or L), a LC CDR1 comprising the amino acid sequence of QX8IGSX9 (SEQ ID NO: 36) (wherein X8 is S or R and X9 is S or H), a LC CDR2 comprising the amino acid sequence of YAS and / or HQSSX 10 EPYT (SEQ ID NO: 38) (wherein X 10 is T, R, or S).

[0044] In yet another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that cross-competes with the binding to CD22 (e.g., human CD22) of any antibody or antigen-binding fragment described herein.

[0045] In some embodiments, the antibodies described herein are recombinant antibodies.

[0046] In some embodiments, the antibodies or antigen-binding fragments thereof described herein cross-react with CD22 from a non-human primate, such as a rhesus monkey.

[0047] In some embodiments, the antibodies described herein are human antibodies.

[0048] In some embodiments, the antibodies or antigen-binding fragments thereof described herein comprise a heavy chain constant region.

[0049] In some embodiments, the antibodies or antigen-binding fragments thereof described herein comprise a heavy chain constant region.

[0050] In some embodiments, the antibodies or antigen-binding fragments described herein are derived from antibodies and are fragments of IgG1, IgG2 and IgG3, IgG4, and IgM, and IgA1, and IgA2, and IgD or IgE antibodies. In some embodiments, the isolated antibodies or antigen-binding fragments described herein are derived from antibodies and are fragments of IgG1 or IgG4 antibodies.

[0051] In some embodiments, the antibodies or antigen-binding fragments thereof described herein further comprise a heterologous moiety. In some embodiments, for example, when the heterologous moiety is a polypeptide, the antibody or antigen-binding fragment thereof can be a fusion protein with such a heterologous moiety. In some embodiments, the antibody or antigen-binding fragment thereof can be conjugated to a heterologous moiety. The heterologous moiety can be, for example, a cytotoxic agent, a cytostatic agent, a radionuclide, or a detectable label. In some embodiments, the heterologous moiety can be, for example, a heterologous polypeptide, a therapeutic agent (e.g., a toxin or drug), or a detectable label, such as, for example, a radioactive label, an enzymatic label, a fluorescent label, or a luminescent label, or an affinity tag, such as biotin or streptavidin. Suitable radiolabels include, for example, 32 P, 33 P, 14 C. 125 I, 131 I, 35 S and 3H. Suitable fluorescent labels include, but are not limited to, fluorescein, fluorescein isothiocyanate (FITC), green fluorescent protein (GFP), DyLight™ 488, phycoerythrin (PE), propidium iodide (PI), PerCP, PE-Alexa Fluor® 700, Cy5, allophycocyanin, and Cy7. Luminescent labels include, for example, any of a variety of luminescent lanthanide (e.g., europium or terbium) chelates. For example, suitable europium chelates include the europium chelates of diethylenetriaminepentaacetic acid (DTPA) or tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Enzymatic labels include, for example, alkaline phosphatase, CAT, luciferase, and horseradish peroxidase.

[0052] In another aspect, the disclosure features a fusion protein including an antibody or antigen-binding fragment thereof described herein.

[0053] In another aspect, the disclosure features a bispecific or multispecific polypeptide comprising two or more different antigen-binding domains, wherein at least one of the two or more different antigen-binding domains comprises an antibody or antigen-binding fragment thereof described herein.

[0054] In yet another aspect, the disclosure features an isolated nucleic acid encoding a polypeptide, wherein the polypeptide is or includes one or more of an antibody or antigen-binding fragment thereof described herein, any of the fusion proteins described herein, or any of the bispecific or multispecific polypeptides described herein.

[0055] In another aspect, the disclosure features expression vectors that include one or more nucleic acids described herein. Also featured are cells (e.g., recombinant cells) that include any of the nucleic acids and / or expression vectors described herein.

[0056] In another aspect, the disclosure features methods of expressing a polypeptide, the methods including culturing a cell, a recombinant cell, or a plurality of such cells or recombinant cells under conditions suitable for expression of the polypeptide from the expression vector by the one or more cells. In some embodiments, the methods can further include isolating the polypeptide from the one or more cells and / or the culture medium in which the one or more cells are cultured. Also featured are isolated polypeptides produced from the methods described herein.

[0057] In yet another aspect, the disclosure features a pharmaceutical composition that includes (i) any one or more of the antibodies or antigen-binding fragments thereof described herein, (ii) any one or more of the fusion proteins described herein, (iii) any one or more of the bispecific or multispecific polypeptides described herein, (iv) any one or more of the nucleic acids described herein, (v) any one or more of the expression vectors described herein, (vi) any one or more of the recombinant cells described herein, and / or (vii) any one or more of the isolated polypeptides described herein; and (b) a pharmaceutically acceptable carrier or excipient.

[0058] In yet another aspect, the disclosure features a method of treating a B cell disorder, the method including administering to a subject having a B cell disorder an effective amount of a therapeutic agent, thereby treating the B cell disorder, wherein the therapeutic agent is or includes: (i) any one or more of the antibodies or antigen-binding fragments thereof (including conjugates) described herein; (ii) any one or more of the fusion proteins described herein; (iii) any one or more of the bispecific or multispecific polypeptides described herein; (iv) any one or more of the nucleic acids described herein; (v) any one or more of the expression vectors described herein; (vi) any one or more of the recombinant cells described herein; (vii) any one or more of the isolated polypeptides described herein; and / or (viii) any one or more of the pharmaceutical compositions described herein.

[0059] In some embodiments, the B cell disorder is an autoimmune disease, for example, the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), myasthenia gravis, Graves' disease, or immune thrombocytopenic purpura (ITP).

[0060] In some embodiments, the B cell disorder is cancer. The cancer can be, for example, a B cell lymphoma, such as non-Hodgkin's lymphoma. The non-Hodgkin's lymphoma can be, for example, Burkitt's lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma, follicular lymphoma, or mantle cell lymphoma.

[0061] In yet another aspect, the disclosure features a method of preventing, reducing, slowing, or inhibiting the proliferation and / or growth of cancer cells, comprising contacting the cancer cells with a therapeutic agent that binds to CD22 expressed on the surface of the cancer cells, where the therapeutic agent is (i) any one or more of the antibodies or antigen-binding fragments thereof (including conjugates) described herein, (ii) any one or more fusion proteins described herein, (iii) any one or more bispecific or multispecific polypeptides described herein, (iv) any one or more recombinant cells described herein, (v) any one or more isolated polypeptides described herein, and / or (vi) any one or more pharmaceutical compositions described herein.

[0062] In certain embodiments, the therapeutic agent may be administered by injection via intravenous, intraperitoneal, intracerebral (intraparenchymal), intraventricular, intramuscular, subcutaneous, intraocular, intraarterial, intracentral, or intrathecal routes, by sustained release system, or implantation device, hi certain embodiments, the composition may be administered by bolus injection, or continuously by infusion, or by implantable device.

[0063] In some aspects, the present disclosure provides a chimeric antigen receptor (CAR) comprising an anti-CD22 antibody described herein.

[0064] In some embodiments, the CAR further comprises a hinge region. In some embodiments, the CAR further comprises a transmembrane domain. In some embodiments, the CAR further comprises an intracellular domain. In some embodiments, the CAR further comprises a costimulatory domain.

[0065] In some aspects, the present disclosure provides an isolated nucleic acid encoding an anti-CD22 CAR described herein.

[0066] In some embodiments, the present disclosure provides an expression vector comprising an isolated nucleic acid encoding an anti-CD22 CAR described herein.

[0067] In some embodiments, the present disclosure provides an immune cell that expresses an anti-CD22 CAR described herein. In some embodiments, the immune cell comprises an isolated nucleic acid or expression vector encoding the anti-CD22 CAR.

[0068] In some embodiments, the immune cell is a T cell, an NK cell, or an NKT cell.

[0069] In some embodiments, the present disclosure provides a composition comprising an immune cell expressing an anti-CD22 CAR and a pharmaceutically acceptable carrier.

[0070] In some aspects, the present disclosure provides methods of treating a B cell disorder described herein. In some embodiments, the immune cells are administered intravenously. In some embodiments, the immune cells are administered subcutaneously.

[0071] The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate certain embodiments and, together with the written description, serve to provide non-limiting examples of certain aspects of the compositions and methods disclosed herein. [Brief explanation of the drawings]

[0072] [Figure 1A]1A-1D are sensorgrams showing the detector response versus time for the interaction of CD22 mAb-1 (FIG. 1A), mAb-2 (FIG. 1B), mAb-3 (FIG. 1C), and mAb-4 (FIG. 1D) with immobilized recombinant human CD22. [Figure 1B] 1A-1D are sensorgrams showing the detector response versus time for the interaction of CD22 mAb-1 (FIG. 1A), mAb-2 (FIG. 1B), mAb-3 (FIG. 1C), and mAb-4 (FIG. 1D) with immobilized recombinant human CD22. [Figure 1C] 1A-1D are sensorgrams showing the detector response versus time for the interaction of CD22 mAb-1 (FIG. 1A), mAb-2 (FIG. 1B), mAb-3 (FIG. 1C), and mAb-4 (FIG. 1D) with immobilized recombinant human CD22. [Figure 1D] 1A-1D are sensorgrams showing the detector response versus time for the interaction of CD22 mAb-1 (FIG. 1A), mAb-2 (FIG. 1B), mAb-3 (FIG. 1C), and mAb-4 (FIG. 1D) with immobilized recombinant human CD22. DETAILED DESCRIPTION OF THE INVENTION

[0073] The present disclosure is based, at least in part, on the development of anti-CD22 antibodies and variants thereof that have demonstrated high binding affinity and specificity for CD22. Uses of the anti-CD22 antibodies and variants thereof in research, diagnostic / detection, and therapeutic applications are also provided.

[0074] These and other aspects, implementations, acts, functionality, features, and embodiments of the present teachings may be more fully understood from the following description taken in conjunction with the accompanying drawings.

[0075] I. Definition Administration: As used herein, the terms "administering" or "administration" mean providing an antibody or composition thereof to a subject in a physiologically and / or pharmacologically useful manner (e.g., to treat a condition in the subject).

[0076] Affinity matured antibody: As used herein, an "affinity matured antibody" refers to an antibody with one or more changes in one or more CDRs that result in an improvement in the affinity (i.e., KD, kd, or ka) of the antibody for a target antigen compared to a parent antibody lacking the changes. Exemplary affinity matured antibodies have nanomolar or even picomolar affinity for the target antigen. Various procedures for producing affinity matured antibodies are known in the art, including screening combinatorial antibody libraries prepared using biodisplay. For example, Marks et al., Biotechnology, 10:779-783 (1992) describe affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and / or framework residues has been described by Barbas et al., Proc. Nat. Acad. Sci. USA, 91:3809-3813 (1994); Schier et al., Gene, 169:147-155 (1995); Yelton et al., J. Immunol., 155:1994-2004 (1995); Jackson et al., J. Immunol., 154(7):3310-3319 (1995), and Hawkins et al., J. Mol. Biol., 226:889-896 (1992). Selective mutations at contact or hypermutation positions with selectively mutagenized and activity-enhancing amino acid residues are described in U.S. Pat. No. 6,914,128 B1.

[0077] Antibody: As used herein, the term "antibody" refers to a polypeptide that comprises at least one immunoglobulin variable domain or at least one site, e.g., a paratope, that specifically binds to an antigen. In some embodiments, an antibody comprises a paratope. In some embodiments, the paratope comprises one or more complementarity-determining regions (CDRs). In some embodiments, an antibody is a full-length antibody. In some embodiments, an antibody is a chimeric antibody. In some embodiments, an antibody is a humanized antibody. However, in some embodiments, an antibody is a Fab fragment, a F(ab')2 fragment, an Fv fragment, or an scFv fragment. In some embodiments, an antibody is a nanobody derived from a camelid antibody or a nanobody derived from a shark antibody. In some embodiments, an antibody is a diabody. In some embodiments, an antibody comprises a framework with human germline sequences. In another embodiment, an antibody comprises a heavy chain constant domain selected from the group consisting of an IgG, IgG1, IgG2, IgG2a, IgG2b, IgG2C, IgG3, IgG4, IgA1, IgA2, IgD, IgM, and IgE constant domain. In some embodiments, an antibody comprises a heavy (H) chain variable region (abbreviated herein as VH) and / or a light (L) chain variable region (abbreviated herein as VL). In some embodiments, an antibody comprises a constant domain, e.g., an Fc region. An immunoglobulin constant domain refers to a heavy or light chain constant domain. Human IgG heavy and light chain constant domain amino acid sequences and functional variants thereof are known. With respect to the heavy chain, in some embodiments, the heavy chain of an antibody described herein can be an alpha (α), delta (Δ), epsilon (ε), gamma (γ), or mu (μ) heavy chain. In some embodiments, the heavy chain of an antibody described herein can comprise a human alpha (α), delta (Δ), epsilon (ε), gamma (γ), or mu (μ) heavy chain. In certain embodiments, the antibodies described herein comprise a human gamma 1 CH1, CH2, and / or CH3 domain. In some embodiments, a V HThe amino acid sequence of the V domain comprises the amino acid sequence of a human gamma (γ) heavy chain constant region known in the art. Non-limiting examples of human constant region sequences are described, for example, in U.S. Patent No. 5,693,780 and Kabat EA et al., (1991) supra. In some embodiments, the V HThe domain comprises an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to any of the variable chain constant regions provided herein. In some embodiments, the antibody is modified, for example, via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, the antibody is a glycosylated antibody conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecules are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecules are branched oligosaccharides or branched glycans. In some embodiments, the one or more sugar or carbohydrate molecules comprise a mannose unit, a glucose unit, an N-acetylglucosamine unit, or a phospholipid unit. In some embodiments, the antibody is a construct comprising a polypeptide comprising one or more antigen-binding fragments of the present disclosure linked to a linker polypeptide or immunoglobulin constant domain. A linker polypeptide comprises two or more amino acid residues linked by a peptide bond and is used to link one or more antigen-binding moieties. Examples of linker polypeptides have been reported (see, e.g., Holliger, P., et al. (1993) Proc. Natl. Acad. Sci. USA 90:6444-6448; Poljak, RJ, et al. (1994) Structure 2:1121-1123). Furthermore, the antibody can be part of a larger immunoadhesion molecule formed by covalent or noncovalent binding of the antibody or antibody portion to one or more other proteins or peptides.Examples of such immunoadhesion molecules include the use of streptavidin core regions to generate tetrameric scFv molecules (Kipriyanov, SM, et al. (1995) Human Antibodies and Hybridomas 6:93-101) and the use of cysteine ​​residues, marker peptides, and C-terminal polyhistidine tags to generate bivalent and biotinylated scFv molecules (Kipriyanov, SM, et al. (1994) Mol. Immunol. 31:1047-1058). In some embodiments, antibodies may be bispecific and multispecific antibodies.

[0078] Approximately: As used herein, the term "approximately" or "about," when applied to one or more subject values, refers to a value similar to a stated reference value. In certain embodiments, the term "approximately" or "about" refers to a range of values ​​that falls within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in either direction of (greater than or less than) the stated reference value, unless otherwise specified or clear from the context (except where such number exceeds 100% of a possible value).

[0079] CDR: As used herein, the term "CDR" refers to a complementarity-determining region within an antibody variable sequence. A typical antibody molecule contains a heavy chain variable region (VH) and a light chain variable region (VL), which are typically involved in antigen binding. The VH and VL regions are further subdivided into regions of hypervariability, also known as complementarity-determining regions (CDRs), which may be interspersed with more conserved regions known as framework regions (FRs). Each VH and VL is typically composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework regions and CDRs can be precisely defined using methodologies known in the art, such as the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the contact definition, all of which are well known in the art.For example, Kabat, EA, et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USDepartment of Health and Human Services, NIH Publication No. 91-3242; IMGT (registered trademark), the international ImMunoGeneTics information system (registered trademark) http: / / www.imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res.,27:209-212(1999);Ruiz,M.et al.,Nucleic Acids Res.,28:219-221(2000);Lefranc,M.-P.,Nucleic Acids Res.,29:207-209(2001);Lefranc,M.-P.,Nucleic Acids Res.,31:307-310(2003);Lefranc,M.-P.et al.,In Silico Biol.,5,0006(2004)[[Epub]],5:45-60(2005);Lefranc,M.-P.et al.,Nucleic Acids Res.,33:D593-597(2005);Lefranc,M.-P.et al.,Nucleic Acids Res.,37:D1006-1012(2009);Lefranc,M.-P.et al.,Nucleic Acids Res.,43:D413-422(2015);Chothia et al.,(1989)Nature 342:877;Chothia,C.et al. (1987) J. Mol. Biol. 196:901-917, Al-lazikani et al. See also, al (1997) J. Molec. Biol. 273:927-948 and Almagro, J. Mol. Recognit. 17:132-143 (2004). hgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, CDRs may refer to CDRs defined by any method known in the art.Two antibodies with the same CDRs mean that the two antibodies have the same amino acid sequence of the CDR as determined by the same method, for example, the IMGT definition.

[0080] In certain embodiments, each of the heavy and light chain variable regions has three CDRs, designated CDR1, CDR2, and CDR3 for each variable region. As used herein, the term "CDR set" refers to a group of three CDRs present in a single variable region that is capable of binding to an antigen. The exact boundaries of these CDRs have been defined differently according to various methods. The scheme described by Kabat (Kabat et al., Sequences of Proteins of Immunological Interest (National Institutes of Health, Bethesda, Md. (1987) and (1991)) not only provides an unambiguous residue numbering system applicable to any antibody variable region, but also provides precise residue boundaries defining the three CDRs. These CDRs may be referred to as Kabat CDRs. Subportions of the CDRs are designated as LC CDR1, LC CDR2, and LC CDR3 or HC CDR1, HC CDR2, and HC CDR3, where "LC" and "HC" refer to the light chain and heavy chain regions, respectively. These regions are sometimes referred to as Chothia CDRs, and have boundaries that overlap with the Kabat CDRs. Other boundaries defining CDRs that overlap with the Kabat CDRs are described by Padlan (FASEB J. 9:133-139 (1995)) and MacCallum (J Mol Biol 262(5):732-45 (1996)). Still other CDR boundary definitions may not strictly adhere to one of the above schemes, but may nonetheless overlap with the Kabat CDRs, but may be shortened or extended to take into account predicted or experimental findings that particular residues or groups of residues, or even entire CDRs, do not significantly affect antigen binding. While the methods used herein may utilize CDRs defined according to any of these schemes, preferred embodiments use CDRs defined by Kabat or Chothia.

[0081] In certain embodiments, the CDRs of an antibody may have different amino acid sequences when different definition systems are used (e.g., the IMGT definition, the Kabat definition, or the Chothia definition). The definition systems number each amino acid in a given antibody sequence (e.g., a VH or VL sequence), and the numbers corresponding to the heavy and light chain CDRs are provided in Table 2. The CDRs listed in Table 1 are defined according to the Kabat definition. One of skill in the art can derive CDR sequences using the different numbering systems of the anti-CD22 antibodies provided in Table 1.

[0082] [Table 1]

[0083] CDR-grafted antibody: The term "CDR-grafted antibody" refers to an antibody that contains heavy and light chain variable region sequences from one species, but in which the sequences of one or more of the VH and / or VL CDR regions have been replaced with CDR sequences from another species, e.g., an antibody having murine heavy and light chain variable regions in which one or more of the murine CDRs (e.g., CDR3) have been replaced with human CDR sequences.

[0084] Chimeric antibody: The term "chimeric antibody" refers to an antibody that contains heavy and light chain variable region sequences from one species and constant region sequences from another species, such as an antibody having murine heavy and light chain variable regions linked to a human constant region.

[0085] Complementary: As used herein, the term "complementary" refers to the capacity for precise pairing between two nucleotides or two sets of nucleotides. In particular, complementary is a term that characterizes the degree of hydrogen bond pairing that results in binding between two nucleotides or two sets of nucleotides. For example, if a base at one position in an oligonucleotide can hydrogen bond with a base at the corresponding position in a target nucleic acid (e.g., mRNA), the bases are considered complementary to each other at that position. Base pairing can include both standard Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for purposes of complementary base pairing, adenosine-type bases (A) are complementary to thymidine-type bases (T) or uracil-type bases (U), cytosine-type bases (C) are complementary to guanosine-type bases (G), and universal bases such as 3-nitropyrrole or 5-nitroindole can hybridize with and are considered complementary to any A, C, U, or T. Inosine (I) is also considered a universal base in the art and is considered complementary to any A, C, U, or T.

[0086] Compete: As used herein with respect to antibodies, the term "compete" means that a first antibody binds to an epitope of a protein (e.g., CD22) in a manner sufficiently similar to the binding of a second antibody, such that the result of binding of the first antibody to its epitope is detectably reduced in the presence of the second antibody compared to binding of the first antibody in the absence of the second antibody. Alternatively, the binding of the second antibody to its epitope is detectably reduced in the presence of the first antibody, but this is possible, though not required. That is, a first antibody may inhibit binding of a second antibody to its epitope without that second antibody inhibiting binding of the first antibody to its respective epitope. However, if each antibody detectably inhibits binding of the other antibody with its epitope or ligand, whether to the same, greater, or lesser extent, the antibodies are said to "cross-compete" with each other for binding of their respective epitopes. In some embodiments, competing or cross-competing antibodies bind to the same or overlapping epitopes. Regardless of the mechanism by which such competition or cross-competition occurs (e.g., steric hindrance, conformational change, or binding to a common epitope or portion thereof), one of skill in the art will understand that such competing and / or cross-competing antibodies are encompassed and may be useful in the methods and / or compositions provided herein.

[0087] Conjugate: As used herein, "conjugate" means two entities associated, preferably with sufficient affinity, such that the therapeutic / diagnostic benefit of the association between the two entities is realized. The association between the two entities can be direct or via a linker, such as a polymer linker. Conjugates can include covalent or non-covalent bonds as well as other forms of association, such as one entity on or within the other, or one or both entities on or within a third entity, such as a micelle.

[0088] Conservative amino acid substitution: As used herein, "conservative amino acid substitution" refers to an amino acid substitution that does not change the relative charge or size characteristics of the protein in which the amino acid substitution is made. Variants can be prepared according to methods for modifying polypeptide sequences known to those skilled in the art, and can be found, for example, in references compiling such methods, such as Molecular Cloning: A Laboratory Manual, J. Sambrook, et al., eds., Fourth Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F.M.Ausubel, et al., eds., John Wiley & Sons, Inc., New York. Conservative amino acid substitutions include substitutions between amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D.

[0089] Cross-reactivity: As used herein, in reference to a targeted agent (e.g., an antibody), the term "cross-reactivity" refers to the property of an agent that can specifically bind to two or more antigens of the same type or class (e.g., multiple homologous, paralogous, or orthologous antigens) with similar affinity or avidity. For example, in some embodiments, an antibody that is cross-reactive to human and non-human primate antigens of the same type or class (e.g., human CD22 and non-human primate CD22) can bind to the human antigen and the non-human primate antigen with similar affinity or avidity. In some embodiments, an antibody is cross-reactive to human and rodent antigens of the same type or class. In some embodiments, an antibody is cross-reactive to rodent and non-human primate antigens of the same type or class. In some embodiments, an antibody is cross-reactive to human, non-human primate, and rodent antigens of the same type or class.

[0090] Cytotoxic Agent: As used herein, the term "cytotoxic agent" refers to a substance that inhibits or prevents cellular function and / or causes cell death or destruction. Such agents are well known in the art and include, for example, radioactive isotopes (e.g., At211, I131, I125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212, and radioactive isotopes of Lu), chemotherapeutic agents or drugs (e.g., methotrexate, adriamycin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin, or other intercalating agents), growth inhibitory agents, enzymes and fragments thereof, such as nucleases, antibiotics, toxins (including fragments and / or variants thereof), such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant, or animal origin, and various antitumor or anticancer agents, as described below.

[0091] Chemotherapeutic Agent: As used herein, "chemotherapeutic agent" refers to a chemical compound useful in the treatment of proliferative disorders such as cancer (e.g., cancers that express CD22). These agents include, for example, alkylating agents such as thiotepa and cyclophosphamide (CYTOXAN®), alkylsulfonates such as busulfan, improsulfan, and piposulfan, aziridines such as benzodopa, carboquone, methouredopa, and uredopa, altretamine, ethylenimines and methylamelamines, including triethylenemethamine, triethylenephosphoramide, triethylenethiophosphoramide, and trimethylolmelamine, acetogenins, and the like. (especially bullatacin and bullatacinone), delta-9-tetrahydrocannabinol (dronabinol, MARINOL), beta-rapachona, lapachol, colchicine, betulinic acid, camptothecin (including synthetic analogs topotecan (HYCAMTIN®), CPT-11 (irinotecan, CAMPTOSAR), acetylcamptothecin, scopolecin, and 9-aminocamptothecin), bryostatin, kallistatin, CC-1065 (adozelesin, carzelesin and its synthetic analogues of bizelesin), podophyllotoxin, podophyllic acid, teniposide, cryptophycins (especially cryptophycin 1 and cryptophycin 8), dolastatins, duocarmycins (including synthetic analogues, KW-2189 and CB1-TM1), eleutherobin, pancratistatin, sarcoditina, pongistatin, chlorambucil, chlornaphazine, colofosfamide, estramustine, ifosfamide, mechlorethrin amine, mechlorethamine oxide hydrochloride, melphalan, nobuenbiquin, phenesterine, prednimustine, trofosfamide, nitrogen mustards such as uracil mustard, nitrosoureas such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimustine, antibiotics such as enediyne antibiotics (e.g., calicheamicin, particularly gamma calicheamicin and omega calicheamicin (see, e.g., Agnew, Chem Intl. Ed. Engl., 33:183-186 (1994))), dynemicins (including dynemicin A),esperamicin and neocarzinostatin chromophores and related chromoprotein antibiotic chromophores), aclacinomycin, actinomycin, autramycin, azaserine, bleomycin, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycin, dactinomycin, daunorubicin, detorubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin, and deoxydoxorubicin) (including epirubicin, esorubicin, idarubicin, marcelomycin, mitomycins such as mitomycin C, mycophenolic acid, nogalamycin, olivomycin, peplomycin, porfiromycin, puromycin, queramycin, rodorbubicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin, antimetabolites such as methotrexate and 5-fluorouracil (5-FU), folates such as denopterin, methotrexate, pteropterin, trimetrexate purine analogues such as fludarabine, 6-mercaptopurine, thiamiprine, and thioguanine; pyrimidine analogues such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocitabine, and floxuridine; androgens such as calsterone, dromostanolone propionate, epithiostanol, mepitiostane, and testolactone; antiadrenal drugs such as aminoglutethimide, mitotane, and trilostane; folic acid supplements such as floric acid; aceglatone; and aldophosphatase inhibitors such as cefotaxime; Mydoglycosides, aminolevulinic acid, eniluracil, amsacrine, bestravcil, bisantrene, edatraxate, defofamine, demecolcine, diazicon, elfornithine, elliptinium acetate, epothilone, etoglucide, gallium nitrate, hydroxyurea, lentinan, lonidanine, maytansinoids such as maytansine and ansamitocin, mitoguazone, mitoxantrone, mopidamol, nitraelin, pentostatin, phenamet, pirarubicin, losoxantrone, 2-ethylhydrazide, procarbazine,PSK® polysaccharide complex (JHS Natural Products, Eugene, OR), razoxane, rhizoxin, schizophyllano, spirogermanium, tenuazonic acid, triaziquone, 2,2',2''-trichlorotriethylamine, trichothecenes (especially T-2 toxin, veracrine A, roridin A, and anguidin), urethane, vindesine (ELDISINE, FILDESIN), dacarbazine, manomustine, mitobronitol, mitolactol, pipobroman, gacytosine, arabinoside ("Ara-C"), thiotepa, taxoids such as paclitaxel (TAXOL, Bristol-Myers Squibb Oncology, Princeton, NJ), Cremophor Free ABRAXANE™, paclitaxel albumin (American Pharmaceutical Nanoparticle formulations modified with docetaxel (TAXOTERE®, Rhone-Poulenc Rorer, Antony, France), chlorambucil, gemcitabine (GEMZAR), 6-thioguanine, mercaptopurine, methotrexate, platinum analogs such as cisplatin and carboplatin, vinblastine (VELBAN®), platinum, etoposide (VP-16), ifosfamide, mitoxantrone, vincristine (ONCOVIN®), oxaliplatin, leucovorin, vinorelbine (NAVELBINE®), novantrone, edatrexate, daunomycin, aminopterin, ibandronate, topoisomerase inhibitors (VELBAN®), vincristine (ONCOVIN®), oxaliplatin, leucovorin, vinorelbine (NAVELBINE®), vinclovir, ... The therapeutic agent may be a combination of two or more of the foregoing, such as the enzyme inhibitor RFS2000, difluoromethylornithine (DMFO), a retinoid such as retinoic acid, capecitabine (XELODA®), a pharmaceutically acceptable salt, acid, or derivative of any of the above, as well as CHOP, which is an abbreviation for cyclophosphamide, doxorubicin, vincristine, and prednisolone combination therapy, CVP, which is an abbreviation for cyclophosphamide, vincristine, and prednisolone combination therapy, and FOLFOX, which is an abbreviation for the oxaliplatin treatment regimen combined with 5-FU and leucovorin (ELOXATIN™).

[0092] Effective amount: As used herein, "effective amount" refers to the amount of each active agent (e.g., an anti-CD22 antibody) needed to confer a desired effect (e.g., a therapeutic effect on a subject), either alone or in combination with one or more other active agents. In some embodiments, the therapeutic effect is a reduction in CD22 levels or activity and / or alleviation of a disease state (e.g., a B-cell disorder).

[0093] Framework: As used herein, the term "framework" or "framework sequence" refers to the remaining sequence of a variable region minus the CDRs. The exact definition of a CDR sequence can be determined by different methods, and therefore the meaning of a framework sequence is subject to different interpretations accordingly. The six CDRs (LC CDR1, LC CDR2, and LC CDR3 of the light chain and HC CDR1, HC CDR2, and HC CDR3 of the heavy chain) also divide the framework regions of the light and heavy chains into four subregions (FR1, FR2, FR3, and FR4) of each chain, with CDR1 located between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. Without designating a particular subregion as FR1, FR2, FR3, or FR4, the framework region, as referred to by others, represents the combined FRs within the variable region of a single naturally occurring immunoglobulin chain. As used herein, FR refers to one of the four subregions, and FR(s) refers to two or more of the four subregions that make up a framework region. Human heavy and light chain acceptor sequences are known in the art. In one embodiment, acceptor sequences known in the art may be used in the antibodies disclosed herein.

[0094] Human antibody: The term "human antibody," as used herein, is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the present disclosure may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), e.g., in the CDRs, particularly CDR3. However, the term "human antibody," as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences.

[0095] Humanized antibody: The term "humanized antibody" refers to an antibody that contains heavy and light chain variable region sequences derived from a non-human species (e.g., mouse), but H and / or V L "Humanized" refers to antibodies in which at least a portion of the sequence has been altered to be more "human-like," i.e., more similar to human germline variable sequences. One type of humanized antibody is a CDR-grafted antibody, in which human CDR sequences are introduced into non-human VH and VL sequences to replace the corresponding non-human CDR sequences. In one embodiment, humanized anti-CD22 antibodies and antigen-binding portions are provided. Such antibodies can be produced by obtaining a murine anti-CD22 monoclonal antibody using traditional hybridoma technology, followed by humanization using in vitro genetic engineering, such as that disclosed in PCT Publication WO 2005 / 123126A2 by Kasaian et al.

[0096] Humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementarity-determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat, or rabbit having the desired specificity, affinity, and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may comprise residues that are found neither in the recipient antibody nor in the imported CDR or framework sequences, but are included to further refine and optimize antibody performance. In general, humanized antibodies will comprise substantially all of at least one, and typically two, variable domains, with all or substantially all of the CDR regions corresponding to those of a non-human immunoglobulin and all or substantially all of the FR regions being those of a human immunoglobulin consensus sequence. The humanized antibody may also optionally comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. The antibody may have a modified Fc region as described in WO 99 / 58572. Other forms of humanized antibodies have one or more CDRs (1, 2, 3, 4, 5, 6) altered with respect to the original antibody, also referred to as one or more CDRs derived from one or more CDRs from the original antibody. Humanized antibodies may also include affinity maturation.

[0097] In some embodiments, humanization involves replacing the CDRs (e.g., as shown in Table 1) with human variable domains (e.g., IGKV1-NL1 * 01 and IGHV1-3 * In some embodiments, the anti-CD22 antibodies of the present disclosure are humanized variants that include one or more amino acid substitutions (e.g., within the VH framework regions) when compared to any one of the VHs listed in Table 1 and / or one or more amino acid substitutions (e.g., within the VL framework regions) when compared to any one of the VLs listed in Table 1.

[0098] Isolated antibody: As used herein, an "isolated antibody" is intended to refer to an antibody that is substantially free of other antibodies having different antigen specificities (e.g., an isolated antibody that specifically binds to CD22 is substantially free of antibodies that specifically bind to antigens other than CD22). However, an isolated antibody that specifically binds to CD22 may have cross-reactivity to other antigens. Furthermore, an isolated antibody may be substantially free of other intracellular material and / or chemicals.

[0099] Kabat Numbering: The terms "Kabat numbering," "Kaba definitions," and "Kabat labels" are used interchangeably herein. These terms are recognized in the art and refer to a numbering system for amino acid residues that are more variable (i.e., hypervariable) than other amino acid residues in the heavy and light chain variable regions of an antibody or antigen-binding portion thereof (Kabat et al., (1971, Ann. NY Acad. Sci. 190:382-391 and Kabat, EA, et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, USDapartment of Health and Human Services, NIH Publication No. 91-3242). In the heavy chain variable region, the hypervariable region ranges from amino acid positions 31 to 35 of CDR1, from amino acid positions 50 to 65 of CDR2, and from amino acid positions 95 to 102 of CDR3. In the light chain variable region, the hypervariable region ranges from amino acid positions 24 to 34 of CDR1, from amino acid positions 50 to 56 of CDR2, and from amino acid positions 89 to 97 of CDR3.

[0100] Recombinant antibody: The term "recombinant antibody," as used herein, is intended to include all antibodies that are prepared, expressed, generated, or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector introduced into a host cell (as described in more detail in this disclosure), including, for example, antibodies isolated from recombinant, combinatorial human antibody libraries (Hoogenboom HR, (1997) TIB Tech. 15:62-70; Azzazy H., and Highsmith WE, (2002) Clin. Biochem. 35:425-445; Gavilondo JV, and Larrick JW (2002) BioTechniques 29:128-145; Hoogenboom H. and Chames P. (2000) Immunology Today 21:371-378), antibodies isolated from animals (e.g., mice) that are transgenic for human immunoglobulin genes (e.g., Taylor, LD, et al. al. (1992) Nucl. Acids Res. 20:6287-6295; Kelerman S-A, and Green LL (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al (2000) Immunology Today 21:364-370) or any other means, including splicing human immunoglobulin gene sequences to other DNA sequences. In some embodiments, recombinant human antibodies are provided herein. In certain embodiments, such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. However, in certain embodiments, such recombinant human antibodies have been subjected to in vitro mutagenesis (or in vivo somatic mutagenesis, when using transgenic animals for human Ig sequences) to thereby modify the V and constant regions of the recombinant antibodies. H Area and V L The amino acid sequence of the region is human germline V H Sequence and V L Derived from human germline V sequences H Sequence and V L

[0013] The present disclosure provides fully human antibodies capable of binding to human CD22, which may be generated using techniques well known in the art using human Ig phage libraries, such as, but not limited to, those disclosed in PCT Publication WO 2005 / 007699 A2 to Jermutus et al.

[0101] Selective: As used herein, the terms "selective" or "selectively" refer to the ability of a molecule to produce an effect (e.g., inhibit, antagonize, agonize, etc.) associated with its target molecule relative to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that the molecule is able to inhibit the target molecule to an extent that is distinguishable from the reference molecule in an inhibition assay or other inhibition assay. For example, with respect to an inhibitor, the term "selectively inhibit" refers to the ability of the inhibitor to inhibit the target molecule to an extent that is distinguishable from a reference molecule that is substantially uninhibited in an inhibition assay, e.g., allowing for selective inhibition of the target molecule as described herein. Once the reaction is complete, the signal generated by inhibiting the target molecule can be measured. The half-maximum inhibitory concentrations of the target molecule and the reference molecule can be calculated. In some embodiments, the molecules described herein selectively bind to the target molecule. In some embodiments, the molecules described herein selectively inhibit the target molecule (e.g., CD22). In some embodiments, the molecules described herein selectively antagonize the target molecule (e.g., CD22). In some embodiments, the molecules described herein selectively neutralize a target molecule (eg, CD22).

[0102] Specific Binding: As used herein, the term "specifically bind" refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that allows the molecule to be used in a binding assay or other binding context to distinguish the binding partner from an appropriate control. With respect to an antibody, the term "specifically bind" refers to the ability of the antibody to bind to a particular antigen with a degree of affinity or avidity, as described herein, relative to an appropriate reference antigen or antigens, thereby allowing the antibody to be used to distinguish the specific antigen from other antigens. In some embodiments, the antibody binds to a specific antigen with a degree of affinity or avidity that allows the antibody to bind to a specific antigen with a degree of affinity or avidity that allows ... -4 M, 10 -5 M, 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M, 10 -13 K for binding target at or below M D In some embodiments, the antibody specifically binds to CD22.

[0103] Subject: As used herein, the term "subject" refers to a mammal. In some embodiments, the subject is a non-human primate or a rodent. In some embodiments, the subject is a human. In some embodiments, the subject is a patient, e.g., a human patient having or suspected of having a disease. In some embodiments, the subject is a human patient having or suspected of having a B cell disorder and one or more conditions resulting from a B cell disorder.

[0104] Treatment: As used herein, the term "treating" or "treatment" refers to the application or administration of a composition comprising one or more active agents (e.g., anti-CD22 antibodies) to a subject with a target disease or disorder, symptoms of a disease / disorder, or a predisposition to a disease / disorder, with the intent to eradicate, cure, alleviate, palliate, alter, repair, ameliorate, improve symptoms of the disease or predisposition to the disease or disorder, or affect the disorder. Alleviating a target disease / disorder includes delaying or preventing the onset or progression of the disease or reducing the severity of the disease.

[0105] II. Antibodies and Related Compositions (a) Anti-CD22 antibody In some embodiments, the anti-CD22 antibody is an antibody specific for CD22. In some aspects, provided herein are antibodies that bind to human CD22 with high specificity and affinity. In some embodiments, the anti-CD22 antibodies described herein specifically bind to any extracellular epitope or epitopes of CD22 that are exposed to the antibody. In some embodiments, the anti-CD22 antibodies provided herein specifically bind to CD22 from humans, non-human primates, mice, rats, etc. In some embodiments, the anti-CD22 antibodies provided herein bind to human CD22. In some embodiments, the anti-CD22 antibodies described herein bind to an amino acid segment of human or non-human primate CD22. CD22 is a molecule that belongs to the SIGLEC family of lectins. It is found on the surface of mature B cells and, to a lesser extent, on some immature B cells. In some embodiments, CD22 acts as an immunomodulatory molecule (e.g., preventing overactivation of the immune system and the development of autoimmune diseases). In some embodiments, CD22 regulates B cell function and proliferation (see, e.g., Shah et al., Targeting CD22 for the Treatment of B-Cell Malignancies. ImmunoTargets and therapy, 2021, 10, 225-236).

[0106] In some embodiments, the anti-CD22 antibodies described herein specifically bind to human CD22. Exemplary amino acid sequences of human CD22 are listed in NCBI Accession Nos. NP_001172028, NP_001172028.1, NP_001172029, NP_001172029.1, NP_001172030, NP_001172030.1, NP_001265346, NP_001265346.1, NP_001762.2, or NP_001762 and UniProt Accession Nos. A0A087WZQ4, A0A2I3RQA0, A0A2I3T384, A0A2J8QHH2 ... Listed below are A0A2R9BGV8, A0A2R9BHT7, A0A2R9BQF7, A0A5F9D606, G1PJ35, G1STP5, H0VKS5, H2QG24, M0QY05, M0QY14, M0QYP4, M0QZ01, M0QZP5, M0QZR7, M0R0R6, M0R1M2, M0R2M0, M0R2R8, M0R3H1, O60926, O95700, Q0EAF5, Q9UQB1, Q9UQB2, P20273, Q9N1E3, Q9N1E4, Q9N1E5, Q9N1E6.

[0107] In some embodiments, the anti-CD22 antibodies described herein specifically bind to an epitope on human CD22 (e.g., the extracellular domain (ECD) of human CD22 described herein). Exemplary amino acid sequences of the extracellular domain of human CD22 are set forth in any one of SEQ ID NOs: 45-48. Human CD22 complete ECD domains 1-7 (SEQ ID NO: 45) [ka] Human CD22 complete ECD domains 1-7 with Avi-His tag (SEQ ID NO: 46) [ka] Human CD22 complete ECD domains 4-7 with Avi-His tag (SEQ ID NO: 47) [ka] Human CD22 complete ECD domains 1-3 with Avi-His tag (SEQ ID NO: 48) [ka]

[0108] In some embodiments, the anti-CD22 antibodies described herein can bind to a fragment of human CD22 (e.g., a human CD22 described herein), which can be about 5 to about 425 amino acids in length, about 10 to about 400 amino acids in length, about 50 to about 350 amino acids in length, about 100 to about 300 amino acids in length, about 150 to about 250 amino acids in length, about 200 to about 300 amino acids in length, or about 75 to about 150 amino acids in length. The fragment can contain consecutively numbered amino acids derived from human CD22 (e.g., the human CD22 ECD domain set forth in any one of SEQ ID NOS: 45 to 48 described herein).

[0109] In some embodiments, the anti-CD22 antibodies described herein specifically bind to mouse CD22. Exemplary amino acid sequences of mouse CD22 are set forth in NCBI Accession Nos. NP_001036782, NP_001036782.1, NP_033975.3, or NP_033975 and Unipro Accession Nos. P35329, Q3U0M3, Q9JHK8, A0A8B7H4W8, A0A087WQ27, A0A087WQV3, A0A087WR31, A0A087WR96, A0A087WST4, A0A1L1SSS3, A0A6I9LN61, A0A6I9LTY4, A0A6P5PYI2, or A0A6P5Q630.

[0110] In some embodiments, the anti-CD22 antibodies described herein specifically bind to an epitope on mouse CD22 (e.g., the extracellular domain (ECD) of mouse CD22 described herein). An exemplary amino acid sequence of the extracellular domain of mouse CD22 is set forth in SEQ ID NO:37. Mouse CD22 complete ECD domain (SEQ ID NO: 37) [ka]

[0111] In some embodiments, the anti-CD22 antibodies described herein can bind to a fragment of mouse CD22 (e.g., a mouse CD22 described herein), which can be about 5 to about 425 amino acids in length, about 10 to about 400 amino acids in length, about 50 to about 350 amino acids in length, about 100 to about 300 amino acids in length, about 150 to about 250 amino acids in length, about 200 to about 300 amino acids in length, or about 75 to about 150 amino acids in length. The fragment can contain consecutively numbered amino acids derived from mouse CD22 (e.g., the mouse CD22 ECD domain set forth in SEQ ID NO: 37).

[0112] In some embodiments, the anti-CD22 antibodies described herein specifically bind to non-human primate CD22. In some embodiments, the non-human primate is a rhesus monkey. Exemplary amino acid sequences of rhesus monkey CD22 are set forth in NCBI Accession Nos. AFE80881.1, XP_028694578.1, XP_028694577.1, XP_028694576.1, XP_028694575.1, XP_014979162.2, XP_028694574.1 or XP_014979161.2 and Uniprot Accession Nos. A0A1D5QV53, A0A5F7ZI40, A0A5F8AEU2, A0A5F8ALZ1, A0A5F8A9A7, F6W458, F6W485, F6WAA5 or H9G1X2.

[0113] In some embodiments, the anti-CD22 antibodies described herein specifically bind to an epitope on rhesus CD22 (e.g., the extracellular domain (ECD) of rhesus CD22 described herein). In some embodiments, the anti-CD22 antibodies described herein can bind to a fragment of rhesus CD22 (e.g., rhesus CD22 described herein), which can be about 5 to about 425 amino acids in length, about 10 to about 400 amino acids in length, about 50 to about 350 amino acids in length, about 100 to about 300 amino acids in length, about 150 to about 250 amino acids in length, about 200 to about 300 amino acids in length, or about 75 to about 150 amino acids in length. The fragment can comprise consecutively numbered amino acids from rhesus CD22 (e.g., rhesus CD22 described herein).

[0114] In some embodiments, the anti-CD22 antibodies described herein are affinity matured clones. In some embodiments, the anti-CD22 antibodies have at least about 10% affinity of CD22 (e.g., human, mouse, or non-human primate CD22). -4 M, 10 -5 M, 10 -6 M, 10 -7 M, 10 -8 M, 10 -9 M, 10 -10 M, 10 -11 M, 10 -12 M, 10 -13and have a binding affinity (e.g., as indicated by KD) of 100 nM or less. For example, an anti-CD22 antibody of the disclosure may bind to a CD22 protein (e.g., human, mouse, or non-human primate CD22) with an affinity of 5 pM to 500 nM, e.g., 50 pM to 100 nM, 500 pM to 50 nM, 1 nM to 50 nM, 2 nM to 20 nM, 1 nM to 10 nM, 1 nM to 3 nM, or 2 nM to 5 nM. The disclosure also includes antibodies that compete with any of the antibodies described herein for binding to a CD22 protein (e.g., human, mouse, or non-human primate CD22) and have an affinity of 100 nM or less (e.g., 80 nM or less, 50 nM or less, 20 nM or less, 10 nM or less, 5 nM or less, 500 pM or less, 50 pM or less, or 5 pM or less). The affinity and binding kinetics of anti-CD22 antibodies can be tested using any suitable method, including, but not limited to, biosensor technology (e.g., OCTET or BIACORE). In some embodiments, the anti-CD22 antibodies described herein bind to CD22 (e.g., human or non-human primate CD22) with a KD in the nanomolar range.

[0115] Binding affinity (or binding specificity) can be determined by various methods, including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance (SPR), fluorescence-activated cell sorting (FACS), or spectroscopy (e.g., using a fluorescence assay). Exemplary conditions for assessing binding affinity are in HBS-P buffer (10 mM HEPES pH 7.4, 150 mM NaCl, 0.005% (v / v) surfactant P20) and PBS buffer (10 mM PO4-3, 137 mM NaCl, and 2.7 mM KCl). Using these techniques, the concentration of the binding protein can be measured as a function of the target protein concentration. The concentration of the binding protein ([[bound]]) is generally related to the concentration of the free target protein ([[free]]) by the following formula: [[Bound]]=[[Free]] / (Kd+[[Free]])

[0116] It is not necessary to make an exact determination of the K, as it may be sufficient to only have a quantitative measure of affinity as determined using methods such as ELISA or FACS analysis, but this is proportional to the K and can therefore be used for comparisons such as determining whether higher affinity is, for example, 2-fold higher, to obtain a qualitative measure of affinity, or to obtain an inference of affinity by, for example, activity in a functional assay (in vitro or in vivo).

[0117] The heavy chain (HC) and light chain (LC) sequences, heavy chain variable domains (VH) and light chain variable domains (VL), CDR sequences, and heavy and light chain constant region sequences of non-limiting examples of anti-CD22 antibodies are provided in Table 1.

[0118] [Table 2]

[0119] [Table 3]

[0120] [Table 4]

[0121] [Table 5]

[0122] [Table 6]

[0123] In some embodiments, according to the IMGT definition, an anti-CD22 antibody of the disclosure comprises an HC CDR1 comprising the amino acid sequence of GFX1FX2X3YG (SEQ ID NO: 33) (wherein Xi is T or I, X2 is S or R, and X3 is S or N), an HC CDR2 comprising the amino acid sequence of IYYDGX4X5X6 (SEQ ID NO: 34) (wherein X4 is N or S, X5 is K or N, and X6 is K or N), an HC CDR3 comprising the amino acid sequence of ARELTGDAFDX7 (wherein X7 is I or L), an LC CDR1 comprising the amino acid sequence of QX8IGSX9 (wherein X8 is S or R and X9 is S or H), an LC CDR2 comprising the amino acid sequence of YAS, and / or HQSSX 10 EPYT (where X 10 is T, R, or S). The consensus sequence of the anti-CD22 antibodies described herein may also be determined by the Kabat definition or the Chothia definition.

[0124] In some embodiments, an anti-CD22 antibody of the disclosure comprises one or more of the HC CDR (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences from any one of the anti-CD22 antibodies selected from Table 1. In some embodiments, an anti-CD22 antibody of the disclosure comprises the HC CDR1, HC CDR2, and HC CDR3 provided for any one of the antibodies selected from Table 1. In some embodiments, an anti-CD22 antibody of the disclosure comprises one or more of the LC CDR (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences from any one of the anti-CD22 antibodies selected from Table 1. In some embodiments, an anti-CD22 antibody of the disclosure comprises the LC CDR1, LC CDR2, and LC CDR3 provided for any one of the anti-CD22 antibodies selected from Table 1.

[0125] In some embodiments, an anti-CD22 antibody of the present disclosure comprises the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 provided for any one of the anti-CD22 antibodies selected from Table 1. In some embodiments, the antibody heavy and light chain CDR3 domains may play a particularly important role in the binding specificity / affinity of an antibody for an antigen. Thus, an anti-CD22 antibody of the present disclosure may comprise at least the heavy and / or light chain CDR3 of any one of the anti-CD22 antibodies selected from Table 1.

[0126] In some embodiments, the isolated anti-CD22 antibody comprises a heavy chain variable region comprising heavy chain CDR1 (HC CDR1), heavy chain CDR2 (HC CDR2), and heavy chain CDR3 (HC CDR3).

[0127] Also included within the scope of the present disclosure are functional variants of any of the exemplary anti-CD22 antibodies disclosed herein. Functional variants have a V H and / or V L Alternatively, a reference antibody may contain one or more amino acid residue mutations in one or more of the HC CDRs and / or one or more of the LC CDRs, while having substantially similar binding activity and biological activity (e.g., substantially similar binding affinity, binding specificity, inhibitory activity, anti-inflammatory activity, or a combination thereof).

[0128] In some embodiments, any of the disclosed anti-CD22 antibodies have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 sequences from one of the anti-CD22 antibodies selected from Table 1. In some embodiments, the location of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2 or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2 or LC CDR3) regions of an antibody described herein can be varied by one, two, three, four, five, or six amino acid positions, so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived is substantially maintained). For example, in some embodiments, the positions defining the CDRs of any antibody described herein may be altered by shifting the N-terminal and / or C-terminal boundaries of the CDR by one, two, three, four, five, or six amino acids for one or more CDR positions of an antibody described herein, so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived is substantially maintained). In another embodiment, the length of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) regions of an antibody described herein may be varied by one, two, three, four, five, or more amino acids (e.g., shorter or longer), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived is substantially maintained).

[0129] Thus, in some embodiments, the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein can be one, two, three, four, five or more amino acids shorter than one or more of the CDRs described herein (e.g., CDRS from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived is substantially maintained, for example). In some embodiments, the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein can be one, two, three, four, five or more amino acids longer than one or more of the CDRs described herein (e.g., a CDR from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived is substantially maintained, for example). In some embodiments, the amino portion of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein may be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., a CDR from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it was derived is substantially maintained, for example).In some embodiments, the carboxy portion of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein may be extended by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., a CDR from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it was derived is substantially maintained, for example). In some embodiments, the amino portion of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein may be shortened by one, two, three, four, five or more amino acids compared to one or more of the CDRs described herein (e.g., a CDR from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it is derived is substantially maintained, for example). In some embodiments, the carboxy portions of HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein can be shortened by one, two, three, four, five, or more amino acids compared to one or more of the CDRs described herein (e.g., a CDR from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it was derived is substantially maintained, for example). Any method can be used to confirm whether immunospecific binding to CD22 (e.g., human CD22) is maintained, for example, using binding assays and conditions described in the art.

[0130] In some examples, any of the disclosed anti-CD22 antibodies have one or more CDR (e.g., HC CDR or LC CDR) sequences substantially similar to any one of the anti-CD22 antibodies selected from Table 1. For example, an antibody may comprise one or more CDR sequences from any of the anti-CD22 antibodies selected from Table 1 containing up to five, four, three, two, or one amino acid residue mutations compared to the corresponding CDR region in any one of the CDRs provided herein (e.g., a CDR from any of the anti-CD22 antibodies selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% of the binding of the original antibody from which it was derived is substantially maintained, e.g., maintained). In some embodiments, any of the amino acid mutations in any of the CDRs provided herein may be conservative mutations. Conservative mutations can be introduced into CDRs at positions where the residues are unlikely to be involved in interactions with the CD22 protein (e.g., a human CD22 protein), e.g., as determined based on a crystal structure. Some aspects of the present disclosure provide anti-CD22 antibodies comprising one or more of the heavy chain variable (VH) and / or light chain variable (VL) domains provided herein. In some embodiments, any of the VH domains provided herein comprise one or more of the HC CDR sequences (e.g., HC CDR1, HC CDR2, and HC CDR3) provided herein, e.g., any of the CDR-H sequences provided in any one of the anti-CD22 antibodies selected from Table 1. In some embodiments, any of the VL domains provided herein comprise one or more of the CDR-L sequences (e.g., LC CDR1, LC CDR2, and LC CDR3) provided herein, e.g., any of the LC CDR sequences provided in any one of the anti-CD22 antibodies selected from Table 1.

[0131] In some embodiments, anti-CD22 antibodies of the disclosure include any antibody and variants thereof comprising the heavy chain variable domain and / or the light chain variable domain of any one of the anti-CD22 antibodies selected from Table 1. In some embodiments, anti-CD22 antibodies of the disclosure include any antibody comprising the heavy chain variable pair and the light chain variable pair of any of the anti-CD22 antibodies selected from Table 1.

[0132] Aspects of the present disclosure provide anti-CD22 antibodies having heavy chain variable (VH) and / or light chain variable (VL) domain amino acid sequences homologous to any of those described herein. In some embodiments, the anti-CD22 antibodies comprise a heavy chain variable sequence or a light chain variable sequence that is at least 75% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the heavy chain variable sequence and / or any light chain variable sequence of any one of the anti-CD22 antibodies selected from Table 1. In some embodiments, the homologous heavy chain variable amino acid sequence and / or light chain variable amino acid sequence does not vary within any of the CDR sequences provided herein. For example, in some embodiments, a degree of sequence variation (e.g., 75%, 80%, 85%, 90%, 95%, 98%, or 99%) may occur within the heavy chain variable sequence and / or light chain variable sequence excluding any of the CDR sequences provided herein. In some embodiments, any of the anti-CD22 antibodies provided herein comprises heavy chain and light chain variable sequences comprising framework sequences that are at least 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to the framework sequences of any anti-CD22 antibody selected from Table 1.

[0133] In some embodiments, an anti-CD22 antibody of the disclosure is a humanized antibody (e.g., a humanized variant containing one or more CDRs of Table 1). In some embodiments, an anti-CD22 antibody of the disclosure comprises a HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CCDR3 that are the same as the HC CDR1, a HC CDR2, a HC CDR3, a LC CDR1, a LC CDR2, and a LC CCDR3 shown in Table 1, and comprises a humanized heavy chain variable region and / or a humanized light chain variable region.

[0134] In some embodiments, the anti-CD22 antibodies of the disclosure are humanized antibodies comprising a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH of any of the anti-CD22 antibodies listed in Table 1. Alternatively or additionally, the anti-CD22 antibodies of the disclosure are humanized antibodies comprising a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL of any one of the anti-CD22 antibodies listed in Table 1.

[0135] Anti-CD22 mAb-1 and variants In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 55. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 56.

[0136] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, an HC CDR3 having the amino acid sequence of SEQ ID NO: 51, an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0137] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 49, HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and HC CDR3 having the amino acid sequence of SEQ ID NO: 51. As used elsewhere in this disclosure, "total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 52, LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0138] In some embodiments, anti-CD22 antibodies of the disclosure comprise an HC CDR1, an HC CDR2, and an HC CDR3 that, in aggregate, are at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, anti-CD22 antibodies of the disclosure comprise an LC CDR1, an LC CDR2, and an LC CDR3 that, in aggregate, are at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0139] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and / or an LC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0140] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0141] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 55. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 56.

[0142] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO: 55. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL set forth in SEQ ID NO: 56.

[0143] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 55. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 56.

[0144] In some embodiments, an anti-CD22 antibody of this disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 55; alternatively or in addition, an anti-CD22 antibody of this disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 56. In some embodiments, an anti-CD22 antibody of this disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 56.

[0145] Anti-CD22 mAb-2 and variants In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 69. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 70.

[0146] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, an HC CDR3 having the amino acid sequence of SEQ ID NO: 65, an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 68.

[0147] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 63, HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and HC CDR3 having the amino acid sequence of SEQ ID NO: 65. As used elsewhere in this disclosure, "in total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 66, LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and LC CDR3 having the amino acid sequence of SEQ ID NO: 68.

[0148] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that are, in total, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 63, HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and HC CDR3 having the amino acid sequence of SEQ ID NO: 65. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that are, in total, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 66, LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and LC CDR3 having the amino acid sequence of SEQ ID NO: 68.

[0149] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 65. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and / or an LC CDR3 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 68.

[0150] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 65. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 68.

[0151] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 69. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 70.

[0152] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO: 69. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL set forth in SEQ ID NO: 70.

[0153] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 69. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 70.

[0154] In some embodiments, an anti-CD22 antibody of this disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 69; alternatively or in addition, an anti-CD22 antibody of this disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 70. In some embodiments, an anti-CD22 antibody of this disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 69 and a VL comprising the amino acid sequence of SEQ ID NO: 70.

[0155] Anti-CD22 mAb-3 and variants In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 83. Alternatively or additionally, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 84.

[0156] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, an HC CDR3 having the amino acid sequence of SEQ ID NO: 79, an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0157] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 63, HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and HC CDR3 having the amino acid sequence of SEQ ID NO: 79. As used elsewhere in this disclosure, "in total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 80, LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0158] In some embodiments, anti-CD22 antibodies of the disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that are, in total, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 63, HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, anti-CD22 antibodies of the disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that are, in total, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 80, LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0159] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or an LC CDR3 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0160] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0161] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 83. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 84.

[0162] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO: 83. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL set forth in SEQ ID NO: 84.

[0163] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 83. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 84.

[0164] In some embodiments, an anti-CD22 antibody of this disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 83; alternatively or in addition, an anti-CD22 antibody of this disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 84. In some embodiments, an anti-CD22 antibody of this disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 83 and a VL comprising the amino acid sequence of SEQ ID NO: 84.

[0165] Anti-CD22 mAb-4 and variants In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 7. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 8.

[0166] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, an HC CDR3 having the amino acid sequence of SEQ ID NO: 3, an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0167] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. As used elsewhere in this disclosure, "in total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0168] In some embodiments, anti-CD22 antibodies of the disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that are, in aggregate, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that are, in aggregate, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 4, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0169] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0170] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0171] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 7. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 8.

[0172] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO:7. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations compared to the VL set forth in SEQ ID NO:8 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations).

[0173] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 7. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO:8.

[0174] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 7, and alternatively or in addition, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 8. In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 7 and a VL comprising the amino acid sequence of SEQ ID NO: 8.

[0175] Further anti-CD22 antibodies In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 21. Alternatively or additionally, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 22.

[0176] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 17, an HC CDR2 having the amino acid sequence of SEQ ID NO: 18, an HC CDR3 having the amino acid sequence of SEQ ID NO: 3, an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0177] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 17, HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. As used elsewhere in this disclosure, "in total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 19, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0178] In some embodiments, anti-CD22 antibodies of the disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 17, HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, anti-CD22 antibodies of the disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that are collectively at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 19, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0179] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 17, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 that contains no more than three amino acid mutations (e.g., no more than three, no more than two, or no more than one amino acid mutation) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0180] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 17, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0181] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 21. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 22.

[0182] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO: 21. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations compared to the VL set forth in SEQ ID NO: 22 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations).

[0183] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 21. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 22.

[0184] In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 25. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 26.

[0185] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 23, an HC CDR3 having the amino acid sequence of SEQ ID NO: 3, an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0186] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 23, and HC CDR3 having the amino acid sequence of SEQ ID NO: 3. As used elsewhere in this disclosure, "in total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 19, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0187] In some embodiments, anti-CD22 antibodies of the disclosure comprise an HC CDR1, an HC CDR2, and an HC CDR3 that, in aggregate, are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 23, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise an LC CDR1, an LC CDR2, and an LC CDR3 that, in aggregate, are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0188] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 23, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0189] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 23, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 19, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0190] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 25. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 26.

[0191] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO: 25. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL set forth in SEQ ID NO: 26.

[0192] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 25. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 26.

[0193] In some embodiments, anti-CD22 antibodies of the disclosure comprise a heavy chain variable domain HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 31. Alternatively or in addition, anti-CD22 antibodies of the disclosure comprise a light chain variable domain LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 32.

[0194] In some embodiments, according to the Kabat definition system, an anti-CD22 antibody of the disclosure comprises an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 27, an HC CDR3 having the amino acid sequence of SEQ ID NO: 28, an LC CDR1 having the amino acid sequence of SEQ ID NO: 29, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0195] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 27, and HC CDR3 having the amino acid sequence of SEQ ID NO: 28. As used elsewhere in this disclosure, "in total" means that the total number of amino acid mutations in all three heavy chain CDRs is within a defined range. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to LC CDR1 having the amino acid sequence of SEQ ID NO: 29, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0196] In some embodiments, anti-CD22 antibodies of the present disclosure comprise HC CDR1, HC CDR2, and HC CDR3 that are, in aggregate, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to HC CDR1 having the amino acid sequence of SEQ ID NO: 1, HC CDR2 having the amino acid sequence of SEQ ID NO: 27, and HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or in addition, anti-CD22 antibodies of the present disclosure comprise LC CDR1, LC CDR2, and LC CDR3 that are, in aggregate, at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to LC CDR1 having the amino acid sequence of SEQ ID NO: 29, LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0197] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 27, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure include an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 29, an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0198] In some embodiments, an anti-CD22 antibody of the present disclosure comprises an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 27, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 29, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0199] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 31. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 32.

[0200] In some embodiments, anti-CD22 antibodies of the disclosure comprise a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in SEQ ID NO: 31. Alternatively or additionally, anti-CD22 antibodies of the disclosure include a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL set forth in SEQ ID NO: 32.

[0201] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 31. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 32.

[0202] In some embodiments, the anti-CD22 antibodies of the present disclosure are chimeric antibodies that can contain heavy and light chain constant regions derived from a human antibody. A chimeric antibody refers to an antibody having a variable region or a portion of a variable region from a first species and a constant region from a second species. Typically, in these chimeric antibodies, the variable regions of both the light and heavy chains mimic the variable regions of antibodies derived from one species of mammal (e.g., a non-human mammal such as mouse, rabbit, or rat), and the constant portions are homologous to the sequences of antibodies derived from another mammal, such as a human. In some embodiments, amino acid modifications can be made in the variable and / or constant regions.

[0203] In some embodiments, the anti-CD22 antibodies described herein are chimeric antibodies that may contain heavy and light chain constant regions derived from a human antibody. A chimeric antibody refers to an antibody having a variable region or a portion of a variable region from a first species and a constant region from a second species. Typically, in these chimeric antibodies, the variable regions of both the light and heavy chains mimic the variable regions of antibodies derived from one species of mammal (e.g., a non-human mammal such as mouse, rabbit, or rat), while the constant portions are homologous to the sequences of antibodies derived from another mammal, such as a human. In some embodiments, amino acid modifications may be made in the variable and / or constant regions.

[0204] In some embodiments, an anti-CD22 antibody of the present disclosure comprises the VL domain and / or VH domain of any one of the anti-CD22 antibodies selected from Table 1, and comprises a constant region comprising the amino acid sequence of the constant region of an IgG, IgE, IgM, IgD, IgA, or IgY immunoglobulin molecule, of any class (e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2, etc.) or any subclass (e.g., IgG2a and IgG2b) of an immunoglobulin molecule. Non-limiting examples of human constant regions are described in the art, e.g., Kabat EA et al., (1991) supra. An example of a human IgG1 constant region is shown below: [ka]

[0205] In some embodiments, the light chain of any of the anti-CD22 antibodies described herein may further comprise a light chain constant region (CL), which may be any CL known in the art. In some examples, the CL is a kappa light chain. In other examples, the CL is a lambda light chain. In some embodiments, the CL is a kappa light chain. Exemplary sequences are provided below: RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 10).

[0206] Other antibody heavy and light chain constant regions may be used in some embodiments, such as those provided in the IMGT database (www.imgt.org) or www.vbase2.org / vbstat.php, both of which are incorporated herein by reference.

[0207] In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising a VH listed in Table 1 or any variant thereof, and a heavy chain constant region that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to SEQ ID NO: 9. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising a VH listed in Table 1 or any variant thereof, and a heavy chain constant region that contains 20 or fewer amino acid mutations compared to SEQ ID NO: 9 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations). In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising a VH listed in Table 1 or any variant thereof, and a heavy chain constant region set forth in SEQ ID NO:9.

[0208] In some embodiments, the anti-CD22 antibodies described herein comprise a light chain comprising a VL listed in Table 1 or any variant thereof, and a light chain constant region that is at least 80%, at least 85%, at least 90%, at least 95%, or at least 99% identical to SEQ ID NO: 10. In some embodiments, the anti-CD22 antibodies described herein comprise a light chain comprising a VL listed in Table 1 or any variant thereof, and a light chain constant region that contains 20 or fewer amino acid mutations compared to SEQ ID NO: 10 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations). In some embodiments, the anti-CD22 antibodies described herein comprise a light chain comprising a VL listed in Table 1 or any variant thereof, and a light chain constant region set forth in SEQ ID NO: 10.

[0209] Examples of IgG heavy and light chain amino acid sequences of described anti-CD22 antibodies are provided in Table 1 above.

[0210] In some embodiments, an anti-CD22 antibody of the disclosure comprises a heavy chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the heavy chain set forth in SEQ ID NO: 11. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a light chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the light chain set forth in SEQ ID NO: 12. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to SEQ ID NO: 11. Alternatively or additionally, the anti-CD22 antibodies described herein comprise a light chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to SEQ ID NO: 12. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 11. Alternatively or in addition, the anti-CD22 antibodies described herein comprise a light chain comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 11 and a light chain comprising the amino acid sequence of SEQ ID NO: 12.

[0211] In some embodiments, an anti-CD22 antibody of the disclosure comprises a heavy chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the heavy chain set forth in SEQ ID NO: 57. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a light chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the light chain set forth in SEQ ID NO: 58. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to SEQ ID NO: 57. Alternatively or additionally, the anti-CD22 antibodies described herein comprise a light chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to SEQ ID NO: 58. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 57. Alternatively or in addition, the anti-CD22 antibodies described herein comprise a light chain comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 57 and a light chain comprising the amino acid sequence of SEQ ID NO: 58.

[0212] In some embodiments, an anti-CD22 antibody of the disclosure comprises a heavy chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the heavy chain set forth in SEQ ID NO: 71. Alternatively or additionally, the anti-CD22 antibodies of the disclosure comprise a light chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the light chain set forth in SEQ ID NO: 72. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to SEQ ID NO: 71. Alternatively or additionally, the anti-CD22 antibodies described herein comprise a light chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to SEQ ID NO: 72. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 71. Alternatively or additionally, the anti-CD22 antibodies described herein comprise a light chain comprising the amino acid sequence of SEQ ID NO: 72. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 71 and a light chain comprising the amino acid sequence of SEQ ID NO: 72.

[0213] In some embodiments, an anti-CD22 antibody of the disclosure comprises a heavy chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the heavy chain set forth in SEQ ID NO: 85. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a light chain that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the light chain set forth in SEQ ID NO: 86. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to SEQ ID NO: 85. Alternatively or additionally, the anti-CD22 antibodies described herein comprise a light chain comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to SEQ ID NO: 86. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 85. Alternatively or in addition, the anti-CD22 antibodies described herein comprise a light chain comprising the amino acid sequence of SEQ ID NO: 86. In some embodiments, the anti-CD22 antibodies described herein comprise a heavy chain comprising the amino acid sequence of SEQ ID NO: 85 and a light chain comprising the amino acid sequence of SEQ ID NO: 86.

[0214] The anti-CD22 antibodies described herein can be in any antibody format, including, but not limited to, an intact (i.e., full-length) antibody, an antigen-binding fragment thereof (Fab, F(ab'), F(ab')2, Fv), a single-chain antibody, a bispecific antibody, or a nanobody. In some embodiments, the anti-CD22 antibodies described herein are scFvs. In some embodiments, the anti-CD22 antibodies described herein are scFv-Fabs (e.g., scFvs fused to a portion of a constant region).

[0215] In some embodiments, conservative mutations can be introduced into an antibody sequence (e.g., a CDR or framework sequence) at positions where the residues are unlikely to be involved in interactions with the target antigen (e.g., CD22), as determined, for example, based on a crystal structure. In some embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the Fc region (e.g., the CH2 domain (residues 231-340 of human IgG1) and / or the CH3 domain (residues 341-447 of human IgG1) and / or hinge region (numbered according to the Kabat numbering system (e.g., EU index of Kabat)) of an anti-CD22 antibody described herein) to alter one or more functional properties of the antibody, such as serum half-life, complement fixation, Fc receptor binding, and / or antigen-dependent cellular cytotoxicity.

[0216] In some embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the hinge region of the Fc region (CH1 domain) such that the number of cysteine ​​residues in the hinge region is altered (e.g., increased or decreased), e.g., as described in U.S. Patent No. 5,677,425. The number of cysteine ​​residues in the hinge region of the CH1 domain can be altered to, for example, facilitate assembly of the light and heavy chains, or to alter (e.g., increase or decrease) the stability of the antibody, or to facilitate linker conjugation. In some embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the Fc region (e.g., the CH2 domain (residues 231-340 of human IgG1) and / or the CH3 domain (residues 341-447 of human IgG1) and / or the hinge region (numbered according to the Kabat numbering system (e.g., EU index of Kabat))) of an antibody described herein to increase or decrease the affinity of the antibody for an Fc receptor (e.g., an activating Fc receptor) on the surface of an effector cell. Mutations in the Fc region of an antibody that decrease or increase the affinity of the antibody for an Fc receptor and techniques for introducing such mutations into an Fc receptor or a fragment thereof are known to those of skill in the art. Examples of mutations in the Fc receptor of an antibody that can be made to alter the affinity of the antibody for the Fc receptor are described, for example, in Smith P et al., (2012) PNAS 109:6181-6186, U.S. Pat. No. 6,737,056, and WO 02 / 060919, WO 98 / 23289, and WO 97 / 34631, which are incorporated herein by reference.

[0217] In some embodiments, one, two, or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into an IgG constant domain or FcRn-binding fragment thereof (preferably an Fc or hinge-Fc domain fragment) such that the half-life of the antibody is altered (e.g., decreased or increased) in vivo. See, e.g., WO 02 / 060919, WO 98 / 23289, and WO 97 / 34631, and U.S. Pat. Nos. 5,869,046, 6,121,022, 6,277,375, and 6,165,745 for examples of mutations that alter (e.g., decrease or increase) the half-life of an antibody in vivo.

[0218] In some embodiments, one, two, or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into the IgG constant domain or FcRn-binding fragment thereof (preferably the Fc or hinge-Fc domain fragment) to decrease the half-life of the anti-CD22 antibody in vivo. In some embodiments, one, two, or more amino acid mutations (i.e., substitutions, insertions, or deletions) are introduced into the IgG constant domain or FcRn-binding fragment thereof (preferably the Fc or hinge-Fc domain fragment) to increase the half-life of the antibody in vivo. In some embodiments, the antibody may have one or more amino acid mutations (e.g., substitutions) in the second constant (CH2) domain (residues 231-340 of human IgG1) and / or the third constant (CH3) domain (residues 341-447 of human IgG1), numbered according to the EU index of Kabat (Kabat EA et al., (1991) supra). In some embodiments, the IgG1 constant region of an antibody described herein comprises a methionine (M) to tyrosine (Y) substitution at position 252, a serine (S) to threonine (T) substitution at position 254, and a threonine (T) to glutamic acid (E) substitution at position 256 (numbering according to the EU index as per Kabat). See U.S. Pat. No. 7,658,921, incorporated herein by reference. IgG mutants of this type, termed "YTE mutants," have been shown to have a four-fold increased half-life compared to the wild-type form of the same antibody (see Dall'Acqua WF et al., (2006) J Biol Chem 281:23514-24). In some embodiments, the antibody comprises an IgG constant domain comprising one, two, three or more amino acid substitutions at amino acid residues 251-257, 285-290, 308-314, 385-389, and 428-436 (numbering according to the EU index as in Kabat).

[0219] In some embodiments, one, two, or more amino acid substitutions are introduced into the IgG constant domain Fc region to alter the effector function of an anti-CD22 antibody. The effector ligand for which affinity is altered can be, for example, an Fc receptor or the C1 component of complement. This approach is described in further detail in U.S. Pat. Nos. 5,624,821 and 5,648,260 (e.g., L234A and L235A mutations). In some embodiments, deletion or inactivation of the constant region domain (via point mutation or other means) can decrease Fc receptor binding of circulating antibodies, thereby increasing tumor localization. See, for example, U.S. Pat. Nos. 5,585,097 and 8,591,886 for a description of mutations that delete or inactivate constant domains, thereby increasing tumor localization. In some embodiments, one or more amino acid substitutions may be introduced in the Fc region of an antibody described herein to remove potential glycosylation sites in the Fc region, thereby reducing Fc receptor binding (see, e.g., Shields RL et al., (2001) J Biol Chem 276:6591-604).

[0220] In some embodiments, one or more amino acids in the constant region of an anti-CD22 antibody described herein can be substituted with a different amino acid residue such that the antibody has altered Clq binding and / or reduced or eliminated complement-dependent cytotoxicity (CDC). This approach is further described in U.S. Pat. No. 6,194,551 (Idusogie et al.). In some embodiments, one or more amino acid residues in the N-terminal region of the CH2 domain of an antibody described herein are modified to thereby alter the antibody's ability to activate complement. This approach is further described in WO 94 / 29351. In some embodiments, the Fc region of an antibody described herein is modified to increase the antibody's ability to mediate antibody-dependent cellular cytotoxicity (ADCC) and / or increase the antibody's affinity for Fcγ receptors. This approach is further described in WO 00 / 42072. In some embodiments, the heavy and / or light variable domain sequences of the antibodies provided herein can be used to generate, for example, CDR-grafted, chimeric, humanized, or composite human antibodies or antigen-binding fragments, as described elsewhere herein. As will be appreciated by those of skill in the art, any variant, CDR-grafted, chimeric, humanized, or composite antibody derived from any of the antibodies provided herein can be useful in the compositions and methods described herein and retains the ability to specifically bind to CD22, such that the variant, CDR-grafted, chimeric, humanized, or composite antibody binds to CD22 at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% or more compared to the original antibody from which it is derived.

[0221] In some embodiments, the antibodies provided herein contain mutations that confer desirable properties to the antibody. For example, to avoid potential complications due to Fab arm exchange, which is known to occur in natural IgG4 mAbs, the antibodies provided herein may contain a stabilizing "Adair" mutation (Angal S., et al., "A single amino acid substitution abolishes the heterogeneity of chimeric mouse / human (IgG4) antibody," Mol Immunol 30, 105-108; 1993), in which serine 228 (EU numbering; residue 241 in Kabat numbering) is converted to proline, resulting in an IgG1-like hinge sequence. Thus, any of the antibodies may contain a stabilizing "Adair" mutation.

[0222] In some embodiments, the antibody is modified, for example, via glycosylation, phosphorylation, sumoylation, and / or methylation. In some embodiments, the antibody is a glycosylated antibody conjugated to one or more sugar or carbohydrate molecules. In some embodiments, the one or more sugar or carbohydrate molecules are conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glypiation (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules are monosaccharides, disaccharides, oligosaccharides, or glycans. In some embodiments, the one or more sugar or carbohydrate molecules are branched oligosaccharides or branched glycans. In some embodiments, the one or more sugar or carbohydrate molecules comprise a mannose unit, a glucose unit, an N-acetylglucosamine unit, an N-acetylgalactosamine unit, a galactose unit, a fucose unit, or a phospholipid unit. In some embodiments, about 1-10, about 1-5, about 5-10, about 1-4, about 1-3, or about 2 sugar molecules are present. In some embodiments, the glycosylated antibody is fully or partially glycosylated. In some embodiments, the antibody is glycosylated by chemical reaction or enzymatic means. In some embodiments, the antibody is glycosylated in vitro or intracellularly, which may optionally lack an enzyme in the N- or O-glycosylation pathway, e.g., a glycosyltransferase. In some embodiments, the antibody is functionalized with a sugar or carbohydrate molecule as described in WO 2014065661, published May 1, 2014, entitled "Modified antibody, antibody-conjugate and process for the preparation thereof."

[0223] In some embodiments, any one of the anti-CD22 antibodies described herein may comprise a signal peptide (e.g., an N-terminal signal peptide) in the heavy and / or light chain sequence. In some embodiments, the anti-CD22 antibodies described herein comprise any one of the VH and VL sequences, any one of the IgG heavy and light chain sequences, or any one of the F(ab') heavy and light chain sequences described herein, and further comprise a signal peptide (e.g., an N-terminal signal peptide).

[0224] In some embodiments, any one of the antibodies described herein is a multispecific antibody that specifically binds to CD22 and one or more additional target antigens. In some embodiments, the antibody is a bispecific antibody that specifically binds to CD22 and one additional target antigen. In some embodiments, the multispecific or bispecific antibody can be obtained by techniques known in the art. In some embodiments, the one or more additional targets include, but are not limited to, CD3, CD4, CD8, CD20, CD19, CD21, CD23, CD46, CD80, HLA-DR, CD74, CD22, CD14, CD15, CD16, CD123, TCR gamma / delta, NKp46, or KIR.

[0225] In some embodiments, the antibodies described herein are directly or indirectly conjugated to one or more molecular payloads or labels. For example, in some embodiments, the antibodies described herein are conjugated to a molecular payload, e.g., a molecular payload that provides a therapeutic benefit to a subject, e.g., an antibody-drug conjugate (ADC). In some embodiments, the molecular payload can be a small molecule, a protein, a nucleic acid, an oligonucleotide, or any molecular entity that can modulate the activity or function of, e.g., a gene, a protein, and / or a nucleic acid in a cell. In some embodiments, the molecular payload is a cytotoxic agent or a chemotherapeutic agent. In some embodiments, the antibodies described herein are directly or indirectly conjugated to a detectable label, e.g., for diagnostic purposes.

[0226] In some embodiments, the present disclosure also provides fusion proteins comprising an anti-CD22 antibody described herein fused directly or indirectly (e.g., via a linker) to one or more polypeptides or proteins.

[0227] (b) Chimeric Antigen Receptor In some aspects, the present disclosure also contemplates engineering any of the anti-CD22 antibodies to be the extracellular ligand-binding domain of a CAR expressed by a genetically modified immune cell (e.g., T cell, NK cell, or NKT cell) described herein. Aspects of the present disclosure also provide chimeric antigen receptors (CARs) comprising the extracellular ligand-binding domain. In some embodiments, the ligand-binding domain binds to a cell surface marker on a target cell (e.g., B cell). In some embodiments, the ligand-binding domain binds to a cell surface marker on a target cell in a particular disease state (e.g., CD22 on B cells in B cell disorders). Generally, a CAR of the present disclosure (e.g., an anti-CD22 CAR) comprises at least an extracellular domain and an intracellular domain. In some embodiments, the extracellular domain of an anti-CD22 CAR comprises a target-specific binding element (e.g., an antibody that specifically binds to CD22 (e.g., human CD22)), also referred to herein as the ligand-binding domain (also referred to herein as the antigen-binding domain). In some embodiments, the extracellular ligand-binding domain of an anti-CD22 CAR is an antigen-binding domain or a portion thereof. In some embodiments, the extracellular ligand-binding domain of an anti-CD22 CAR is a Fab. In some embodiments, the extracellular ligand-binding domain of an anti-CD22 CAR is an ScFv. In some embodiments, the extracellular ligand-binding domain of a CAR described herein comprises an anti-CD22 antibody or an antigen-binding fragment thereof (e.g., an anti-CD22 antibody). In some embodiments, an anti-CD22 CAR comprises a heavy chain variable domain (VH) HC CDR1, HC CDR2, and HC CDR3 having the amino acid sequence of SEQ ID NO: 7, 55, 69, or 83. Alternatively or additionally, an anti-CD22 CAR comprises a light chain variable domain (VL) LC CDR1, LC CDR2, and LC CDR3 having the amino acid sequence of SEQ ID NO: 8, 56, 70, or 84.In some embodiments, the anti-CD22 CAR comprises: (i) a heavy chain variable domain (VH) comprising an HC CDR1, HC CDR2, and HC CDR3 with the amino acid sequence of SEQ ID NO: 7 and a light chain variable domain (VL) comprising an LC CDR1, LC CDR2, and LC CDR3 with the amino acid sequence of SEQ ID NO: 8; (ii) a heavy chain variable domain (VH) comprising an HC CDR1, HC CDR2, and HC CDR3 with the amino acid sequence of SEQ ID NO: 55 and a light chain variable domain (VL) comprising an LC CDR1, LC CDR2, and LC CDR3 with the amino acid sequence of SEQ ID NO: 56; (iii) a heavy chain variable domain (VH) comprising an HC CDR1, HC CDR2, and HC CDR3 with the amino acid sequence of SEQ ID NO: 69 and a light chain variable domain (VL) comprising an amino acid sequence of SEQ ID NO: 70; or (iv) a heavy chain variable domain (VH) comprising an HC CDR1, HC CDR2, and HC CDR3 with the amino acid sequence of SEQ ID NO: 83. It comprises LC CDR1, LC CDR2 and LC CDR3 of a light chain variable domain (VL) having CDR3 and the amino acid sequence of SEQ ID NO:84.

[0228] In some embodiments, according to the Kabat definition scheme, the anti-CD22 CAR comprises an HC CDR3 having the amino acid sequence of SEQ ID NO: 3, 51, 65, or 79. In some embodiments, according to the Kabat definition scheme, the anti-CD22 CAR comprises (i) an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 3, (ii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 51, (iii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 65, or (iv) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, in some embodiments, according to the Kabat definition scheme, the anti-CD22 CAR comprises (i) an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 54; (iii) an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 68; or (iv) an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.In some embodiments, according to the Kabat definition scheme, the anti-CD22 CAR comprises: (i) an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, an HC CDR3 having the amino acid sequence of SEQ ID NO: 3, an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, an HC CDR3 having the amino acid sequence of SEQ ID NO: 51, an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 54; (iii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, an HC CDR3 having the amino acid sequence of SEQ ID NO: 65, an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 68. CDR3, or (iv) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, an HC CDR3 having the amino acid sequence of SEQ ID NO: 79, an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0229] In some embodiments, the anti-CD22 CAR comprises an HC CDR1, an HC CDR2, and an HC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to (i) an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 51; (iii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 65; or (iv) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or in addition, the anti-CD22 CAR comprises an LC CDR1, LC CDR2 and LC CDR3 that contain a total of five or fewer amino acid mutations (e.g., five or fewer, four or fewer, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to (i) an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 6, (ii) an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 54, (iii) an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 68, or (iv) an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0230] In some embodiments, the anti-CD22 CAR comprises an HC CDR1, HC CDR2, and HC CDR3 that are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical in total to: (i) an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 51; (iii) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 65; or (iv) an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and an HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or in addition, the anti-CD22 CAR comprises an LC CDR1, LC CDR2, and LC CDR3 that are at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical in total to (i) an LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) an LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 54; (iii) an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 68; or (iv) an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0231] In some embodiments, the anti-CD22 CAR comprises: (i) an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1; an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 49; an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 50; and / or an HC CDR3 having the amino acid sequence of SEQ ID NO: 51. (iii) an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and / or an HC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 65, or (iv) an HC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 78. CDR2 and / or HC having the amino acid sequence of SEQ ID NO: 79and an HC CDR3 having three or fewer amino acid mutations compared to CDR3 (eg, three or fewer, two or fewer, or one or fewer amino acid mutations). Alternatively or in addition, these anti-CD22 CARs may comprise: (i) an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 4; an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or an LC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 52; an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 53; and / or an LC CDR3 having the amino acid sequence of SEQ ID NO: 54. (iii) an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and / or an LC CDR3 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR3 having the amino acid sequence of SEQ ID NO: 68, or (iv) an LC CDR1 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, and an LC CDR2 having three or fewer amino acid mutations (e.g., three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 having the amino acid sequence of SEQ ID NO: 81.and / or an LC CDR3 having three or fewer amino acid mutations (eg, three or fewer, two or fewer, or one or fewer amino acid mutations) compared to an LC CDR2 and / or an LC CDR3 having the amino acid sequence of SEQ ID NO:82.

[0232] In some embodiments, the anti-CD22 CAR comprises: (i) an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1; an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 49; an HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 50; an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to CDR2 and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 51; (iii) an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63; an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 64; and / or an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 65. CDR3, or (iv) an HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or an HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an HC CDR3 having the amino acid sequence of SEQ ID NO: 79.Alternatively or in addition, the anti-CD22 CAR may comprise: (i) an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 4; an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 52; an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 53; (iii) an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 66; an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 67; and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 68. CDR3, or (iv) an LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or an LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to an LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0233] In some embodiments, the anti-CD22 CAR comprises a VH comprising the amino acid sequence of SEQ ID NO: 7, 55, 69, or 83. Alternatively or additionally, the anti-CD22 CAR comprises a VL comprising the amino acid sequence of SEQ ID NO: 8, 56, 70, or 84. In some embodiments, the anti-CD22 CAR comprises (i) a VH comprising the amino acid sequence of SEQ ID NO: 7 and a VL comprising the amino acid sequence of SEQ ID NO: 8, (ii) a VH comprising the amino acid sequence of SEQ ID NO: 55 and a VL comprising the amino acid sequence of SEQ ID NO: 56, (iii) a VH comprising the amino acid sequence of SEQ ID NO: 69 and a VL comprising the amino acid sequence of SEQ ID NO: 70, or (iv) a VH comprising the amino acid sequence of SEQ ID NO: 83 and a VL comprising the amino acid sequence of SEQ ID NO: 84.

[0234] In some embodiments, the anti-CD22 CAR comprises a VH that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VH set forth in any of SEQ ID NOs: 7, 55, 69, and 83. Alternatively or in addition, the anti-CD22 CAR comprises a VL that contains 20 or fewer amino acid mutations (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations) compared to the VL set forth in any of SEQ ID NOs: 8, 56, 70, and 84. In some embodiments, the anti-CD22 CAR comprises a VH that contains 20 or fewer amino acid mutations compared to the VH set forth in SEQ ID NO:7 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations), and a VL that contains 20 or fewer amino acid mutations compared to the VL set forth in SEQ ID NO:8 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations).In some embodiments, the anti-CD22 CAR comprises a VH that contains 20 or fewer amino acid mutations compared to the VH set forth in SEQ ID NO: 55 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations), and a VL that contains 20 or fewer amino acid mutations compared to the VL set forth in SEQ ID NO: 56 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations). In some embodiments, the anti-CD22 CAR comprises a VH that contains 20 or fewer amino acid mutations compared to the VH set forth in SEQ ID NO: 69 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations), and a VL that contains 20 or fewer amino acid mutations compared to the VL set forth in SEQ ID NO: 70 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations).In some embodiments, the anti-CD22 CAR comprises a VH that contains 20 or fewer amino acid mutations compared to the VH set forth in SEQ ID NO: 83 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations), and a VL that contains 20 or fewer amino acid mutations compared to the VL set forth in SEQ ID NO: 84 (e.g., 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid mutations).

[0235] In some embodiments, an anti-CD22 CAR comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a VH set forth in any of SEQ ID NOs: 7, 55, 69, and 83. Alternatively or additionally, an anti-CD22 CAR comprises a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a VL set forth in any of SEQ ID NOs: 8, 56, 70, or 84. In some embodiments, an anti-CD22 CAR comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a VH set forth in SEQ ID NO: 7, and a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a VL set forth in SEQ ID NO: 8. In some embodiments, an anti-CD22 CAR comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 55, and a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 56. In some embodiments, an anti-CD22 CAR comprises a VH comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 69, and a VL comprising an amino acid sequence at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 70. In some embodiments, the anti-CD22 CAR comprises a VH comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VH set forth in SEQ ID NO: 83, and a VL comprising an amino acid sequence that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to the VL set forth in SEQ ID NO: 84.

[0236] In some embodiments, the anti-CD22 CAR comprises an extracellular ligand-binding domain comprising a single-chain variable fragment (scFv). In some embodiments, the VH and VL of the anti-CD22 CAR (e.g., anti-CD22 scFv) are linked together by a linker. In some embodiments, the linker can have a length of about 2-10 amino acids, 5-20 amino acids, 10-30 amino acids, 20-50 amino acids, 40-60 amino acids, 60-80 amino acids, or more than 80 amino acids. In some embodiments, the linker can include, but is not limited to, any of those encompassed in U.S. Pat. Nos. 8,445,251 and 9,434,931.

[0237] In some embodiments, an anti-CD22 CAR comprises an extracellular ligand-binding domain comprising an scFv comprising a VH and a VL, wherein the C-terminus of the VH is joined to the N-terminus of the VL via a linker. In some embodiments, an anti-CD22 CAR comprises an extracellular ligand-binding domain comprising an scFv comprising a VH and a VL, wherein the C-terminus of the VL is joined to the N-terminus of the VH via a linker. In some embodiments, an anti-CD22 CAR of the present disclosure further comprises a hinge region. Any suitable known hinge region can be used in the anti-CD22 CARs described herein, such as hinge regions from CD4, CD8, CD28, CD3, IgG1, IgG4, IgD, IgA, or IgM, hybrids, or variants thereof (see, e.g., Jayaraman et al., CAR-T design: Elements and their synergistic function, eBioMedicine, VOLUME 58, 102931, AUGUST 2020); Guedan et al., Engineering and Design of Chimeric Antigen Receptors, Mol Ther Methods Clin Dev. 2019 Mar 15;12:145-156).

[0238] In some embodiments, the anti-CD22 CAR of the present disclosure further comprises a transmembrane domain linking the extracellular ligand-binding domain to the intracellular signaling domain and costimulatory domain. Regarding the transmembrane domain, the CAR can be designed to include a transmembrane domain fused directly or via a hinge region to the extracellular domain (e.g., antigen-binding domain) of the CAR. Any transmembrane domain is contemplated for use herein, as long as it can anchor the CAR containing the domain to the cell membrane. In some embodiments, a transmembrane domain naturally associated with one of the domains in the CAR is used. In some instances, the transmembrane domain may be selected or modified by amino acid substitution to avoid binding of such domain to the transmembrane domain of the same or a different surface membrane protein to minimize interaction with other members of the receptor complex. Those skilled in the art will understand that a complete transmembrane domain or a portion thereof may be implemented with a cytoplasmic domain or a portion thereof. The transmembrane domain may be derived from either natural or synthetic sources. If the source is natural, the domain may be derived from any membrane-bound or transmembrane protein. In some embodiments, the transmembrane domain may be synthetic, in which case it comprises primarily hydrophobic residues such as leucine and valine. Preferably, a phenylalanine, tryptophan, and valine triad will be found at each end of a synthetic transmembrane domain. Optionally, a short oligo- or polypeptide linker, preferably 2-10 amino acids in length, may form the link between the transmembrane domain and the cytoplasmic signaling domain of the CAR. A glycine-serine dibasic pair provides a particularly suitable linker. In some embodiments, the transmembrane domain may be any suitable transmembrane domain known in the art, such as a transmembrane domain derived from TCRα, TCRβ, TCRζ, CD3ζ, CD3ε, CD3γ, CD3δ, CD4, CD5, CD8, CD9, CD16, CD22, CD28, CD32, CD33, CD34, CD37, CD45, CD64, CD80, CD86, CD134, CD137, CD154, or inducible T cell costimulator (ICOS). However, any transmembrane domain is contemplated for use herein as long as it is capable of anchoring a CAR, including its extracellular domain, to a cell membrane.Transmembrane domains are known in the art or can be identified using any of the methods described herein, for example, using the UniProt database.

[0239] In some embodiments, the anti-CD22 CAR further comprises an intracellular (or cytoplasmic) domain. In some embodiments, the intracellular domain of the CAR is involved in activating at least one of the normal effector functions of the immune cell in which the CAR is placed. The term "effector function" refers to a specialized function of a cell (e.g., a T cell, an NK cell, or an NKT cell). The effector function of a cell (e.g., a T cell, an NK cell, or an NKT cell) can be cytolytic activity or helper activity, for example, cytokine secretion. Thus, the term "intracellular signaling domain" refers to a portion of a protein that transduces an effector function signal and causes the cell to perform a specialized function. Typically, the entire intracellular signaling domain can be used, but often it is not necessary to use the entire domain. To the extent that a truncated portion of the intracellular signaling domain is used, such a truncated portion can be used in place of the intact domain, so long as it transduces the effector function signal. Thus, the term intracellular signaling domain is meant to include any truncated portion of the intracellular signaling domain sufficient to transduce the effector function signal. In certain embodiments, the intracellular (or cytoplasmic) domain of a chimeric antigen receptor disclosed herein may include, but is not limited to, a 4-1BB intracellular domain, an OX40 intracellular domain, a CD30 intracellular domain, a CD40 intracellular domain, an ICOS intracellular domain, an LFA-1 intracellular domain, a CD2 intracellular domain, a CD3ζ intracellular domain, a CD3γ intracellular domain, a CD3δ intracellular domain, a CD3ε intracellular domain, a CD7 intracellular domain, and a CD22 intracellular domain.

[0240] In some embodiments, the intracellular domain further comprises one or more intracellular costimulatory domains, such as those described herein, that transduce a costimulatory signal that promotes cell proliferation, cell survival, and / or cytokine secretion after binding of the extracellular domain. In some embodiments, such intracellular costimulatory domains include, but are not limited to, any costimulatory domain disclosed herein or domains known in the art, including, but not limited to, CD28, ICOS, 4-1BB, OX40, or CD27.

[0241] The intracellular signaling domain of the chimeric protein antigen receptor of the present disclosure is responsible for activating at least one of the normal effector functions and / or proliferation and cell survival pathways of the cell in which the CAR is placed.

[0242] It is understood that the chimeric antigen receptors disclosed herein can include domains having sequences described herein (e.g., extracellular domains, transmembrane domains, intracellular (cytoplasmic) domains, costimulatory domains, signaling domains, or any combination thereof), or variants or fragments thereof of any one or more of the domains disclosed herein (e.g., variants and / or fragments that retain the functions necessary for chimeric protein antigen receptor activity).

[0243] III. Preparation of anti-CD22 antibodies Antibodies capable of binding to CD22 as described herein can be produced by any method known in the art. See, e.g., Harlow and Lane, (1998) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York.

[0244] In some embodiments, antibodies specific to a target antigen (e.g., CD22) can be produced by conventional hybridoma technology. A full-length target antigen or a fragment thereof, optionally conjugated to a carrier protein such as KLH, can be used to immunize a host animal to generate antibodies that bind to that antigen. The route and schedule of immunization of the host animal generally follows established and conventional techniques for antibody stimulation and production, as further described herein. General techniques for producing murine, humanized, and human antibodies are known in the art and are described herein. It is contemplated that any mammalian subject, including humans or antibody-producing cells therefrom, can be engineered to serve as the basis for the production of mammalian, including human hybridoma cell lines. Typically, the host animal is administered an amount of an immunogen, including those described herein, intraperitoneally, intramuscularly, orally, subcutaneously, intraplantarly, and / or intradermally.

[0245] If necessary, the desired (monoclonal or polyclonal) antibody (e.g., produced by a hybridoma) can be sequenced, and the polynucleotide sequence can then be cloned into a vector for expression or propagation. The sequence encoding the desired antibody can be maintained within the vector in a host cell, which can then be expanded and frozen for future use. Alternatively, the polynucleotide sequence can be used for genetic engineering to "humanize" the antibody or improve its affinity (affinity maturation) or other characteristics. For example, the constant region can be engineered to more resemble human constant regions to avoid an immune response when the antibody is used in clinical trials and treatments in humans. It may be desirable to genetically engineer the antibody sequence to obtain higher affinity for the target antigen and greater efficacy. It will be apparent to those skilled in the art that one or more polynucleotide changes can be made to an antibody and still maintain its binding specificity for the target antigen.

[0246] In other embodiments, fully human antibodies can be obtained by using commercially available mice engineered to express specific human immunoglobulin proteins. Transgenic animals designed to produce a more desirable (e.g., fully human) or more robust immune response can also be used to produce humanized or human antibodies. Examples of such technologies are Xenomuse™ from Amgen, Inc. (Fremont, CA), HuMAb-Mouse™ and TC Mouse™ from Medarex, Inc. (Princton, NJ), or H2L2 from Harbour Antibodies BV (Holland). In another alternative, antibodies can be engineered by phage display or yeast technology. See, e.g., U.S. Patent Nos. 5,565,332, 5,580,717, 5,733,743, and 6,265,150 and Winter et al., (1994) Annu. Rev. Immunol. 12:433-455. Alternatively, phage display technology (McCafferty et al., (1990) Nature 348:552-553) can be used to produce human antibodies and antibody fragments in vitro, from immunoglobulin variable (V) domain gene repertoires from unimmunized donors.

[0247] Antigen-binding fragments of intact antibodies (full-length antibodies) can be prepared by conventional methods. For example, F(ab')2 fragments can be produced by pepsin digestion of antibody molecules, and Fab fragments can be generated by reducing the disulfide bridges of F(ab')2 fragments. Genetically engineered antibodies, such as humanized antibodies, chimeric antibodies, single-chain antibodies, and bispecific antibodies, can be produced, for example, through conventional recombinant techniques. In one example, DNA encoding a monoclonal antibody specific to a target antigen can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes capable of specifically binding to genes encoding the heavy and light chains of the monoclonal antibody). Hybridoma cells serve as a preferred source of such DNA. Once isolated, the DNA is placed into one or more expression vectors, which are then transfected into host cells such as Escherichia coli (E. coli) cells, simian (COS) cells, Chinese hamster ovary (CHO) cells, human HEK293 cells, or myeloma cells that do not otherwise produce immunoglobulin proteins, resulting in the synthesis of monoclonal antibodies in the recombinant host cells. See, for example, PCT Publication WO 87 / 04462. The DNA can then be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains for the homologous murine sequences (Morris et al., (1984) Proc. Nat. Acad. Sci. 81:6851), or by covalently linking all or part of the coding sequence for a non-immunoglobulin polypeptide to the immunoglobulin coding sequence. In this manner, genetically engineered antibodies, such as "chimeric" or "hybrid" antibodies, can be prepared with the binding specificity of a target antigen.

[0248] Single-chain antibodies can be prepared recombinantly by linking a nucleotide sequence encoding a heavy chain variable region with a nucleotide sequence encoding a light chain variable region, preferably incorporating a flexible linker between the two variable regions.

[0249] Alternatively, techniques described for the production of single-chain antibodies (U.S. Pat. Nos. 4,946,778 and 4,704,692) can be adapted to produce phage or yeast scFv libraries, and CD22-specific scFv clones can be identified from the libraries using routine procedures. Positive clones can be subjected to further screening to identify clones with high CD22 binding affinity.

[0250] Antibodies obtained according to the methods described herein and known in the art can be characterized using methods known in the art. For example, one method is to identify the epitope to which an antigen binds, i.e., "epitope mapping." There are many methods known in the art for mapping and characterizing the location of epitopes on proteins, including solving the crystal structure of antibody-antigen complexes, competitive assays, gene fragment expression assays, and synthetic peptide-based assays, as described, for example, in Chapter 11 of Harlow and Lane, "Using Antibodies," a Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, 1999. In one example, epitope mapping can be achieved using H / D-Ex (hydrogen-deuterium exchange) coupled with proteolysis and mass spectrometry. In a further example, epitope mapping can be used to determine the sequence to which an antibody binds. The epitope can be a linear epitope, i.e., a conformational epitope (linear sequence of primary structure) formed by three-dimensional interactions of amino acids that may not necessarily be contained in a single stretch. Peptides of various lengths (e.g., at least 4-6 amino acids long) can be isolated or synthesized (e.g., recombinantly) and used in antibody binding assays. In another example, the epitope to which an antibody binds can be determined in a systematic screen by using overlapping peptides derived from the target antigen sequence and determining antibody binding. In a gene fragment expression assay, the open reading frame encoding the target antigen is fragmented either randomly or by specific gene construction, and the reactivity of the expressed fragments of the antigen with the antibody being tested is determined. Gene fragments can be generated, for example, by PCR, then transcribed in vitro in the presence of radioactive amino acids and translated into protein. Antibody binding to the radiolabeled antigen fragments is then determined by immunoprecipitation and gel electrophoresis.Specific epitopes can also be identified by using large libraries of random peptide sequences (phage libraries) displayed on the surface of phage particles. Alternatively, a defined library of overlapping peptide fragments can be tested for binding to a test antibody in a simple binding assay. In a further example, mutagenesis of the antigen-binding domain, domain swapping experiments, and alanine scanning mutagenesis can be performed to identify required, sufficient, and / or necessary residues for epitope binding. Alternatively, a competition assay can be performed using other antibodies known to bind to the same antigen to determine whether the antibody binds to the same epitope as the other antibodies. Competition assays are well known to those skilled in the art.

[0251] In some examples, anti-CD22 antibodies are prepared by recombinant techniques, as exemplified below. Nucleic acids encoding the heavy and light chains of the anti-CD22 antibodies described herein can be cloned into an expression vector, with each nucleotide sequence operably linked to a suitable promoter. In one example, the nucleotide sequences encoding the heavy and light chains are each operably linked to a separate promoter. Alternatively, the nucleotide sequences encoding the heavy and light chains can be operably linked to a single promoter such that both the heavy and light chains are expressed from the same promoter. If necessary, an internal ribosome entry site (IRES) can be inserted between the sequence encoding the heavy chain and the sequence encoding the light chain.

[0252] In some instances, the nucleotide sequences encoding the two chains of an antibody are cloned into two vectors that can be introduced into the same cell or different cells. If the two chains are expressed in different cells, each of them can be isolated from such expressing host cells, and the isolated heavy and light chains can be mixed and incubated under suitable conditions to allow antibody formation.

[0253] Generally, a nucleic acid sequence encoding one or all chains of an antibody can be cloned into a suitable expression vector operably linked to a suitable promoter using methods known in the art. For example, the nucleotide sequence and vector can be contacted with a restriction enzyme under suitable conditions to create complementary ends on each molecule that can pair with each other and join together with a ligase. Alternatively, synthetic nucleic acid linkers can be ligated to the ends of the gene. These synthetic linkers contain nucleic acid sequences that correspond to specific restriction sites in the vector. The choice of expression vector / promoter depends on the type of host cell to be used to produce the antibody.

[0254] A variety of promoters can be used to express the antibodies described herein, including, but not limited to, the cytomegalovirus (CMV) intermediate-early promoter, viral LTRs such as Rous sarcoma virus LTR, HIV-LTR, HTLV-1 LTR, Simian Virus 40 (SV40) early promoter, Escherichia coli (E. coli) lac UV promoter, and herpes simplex virus tk promoter.

[0255] Regulatable promoters can also be used, including those that use the lac repressor from Escherichia coli (E. coli) as a transcriptional regulator to control transcription from the lac operator with a mammalian promoter [[Bron, M. et al., Cel, 49:603-612 (1987)]] and the tetracycline repressor (TetR) [[Gossen, M., and Bujard, H., Proc. Natl. Acad. Sci. USA 89:5547-555115 (1992); Yao, F. et al., Human Gene Therapy, 9:1939-1950 (1998); Shockelt, P., et al., Proc. Natl. Acad. Sci. USA 92:6522-6526 (1995)]]. Other systems include FK506 dimers, VP16 or p65 using astroradiol, RU486, diphenol murislerone or rapamycin. Inducible systems are available from Invitrogen, Clontech and Ariad, among others.

[0256] Regulatable promoters containing repressors with operons can be used. In one embodiment, the lac repressor from Escherichia coli (E. coli) functions as a transcriptional modulator to regulate transcription from mammalian cell promoters carrying the lac operator [[M. Bronetal., Cel, 49:603-612 (1987)]]; Gosen and Bujad (1992); [[M. Gosetal. Acad. Sci. USA, 89:5547-5551 (1992)]]. The tetracycline repressor (tetR) and transcription activator (VP16) can be combined to create a tetR-mammalian cell transcription activator fusion protein tTa (tetR-VP16) using a minimal promoter with tetO derived from the human cytomegalovirus (hCMV) promoter, creating a tetR-tet operator system for controlling gene expression in mammalian cells. In one embodiment, a tetracycline-inducible switch is used. When the tetracycline operator is appropriately positioned downstream of the TATA element of the CMVIE promoter, the tetracycline repressor (tetR) alone, but not tetR-mammalian cell transcription factor fusion derivatives, can function as a potent transmodulator to control gene expression in mammalian cells (Yao et al., Human Gene Therapy). One particular advantage of this tetracycline-inducible switch is that it achieves its tunable effect without requiring the use of tetracycline repressor-mammalian cell transactivator or repressor fusion proteins, which can in some cases be toxic to cells (Gossen et al., Natl. Acad. Sci. USA, 89:5547-5551 (1992); Shockett et al., Proc. Natl. Acad. Sci. USA, 92:6522-6526 (1995)).

[0257] In addition, vectors can include, for example, any or all of the following: a selectable marker gene, such as a neomycin gene for selecting stable or transient transfectants in mammalian cells; an enhancer / promoter sequence from the immediate early gene of human CMV for high-level transcription; a transcription termination and RNA processing signal from SV40 for mRNA stability; an SV40 polyoma replication origin and ColE1 for proper episomal replication; an internal ribosome binding site (IRES); a versatile multiple cloning site; and T7 and SP6 RNA promoters for in vitro transcription of sense and antisense RNA. Suitable vectors and methods for producing vectors containing transgenes are well known and available in the art. Examples of polyadenylation signals useful for carrying out the methods described herein include, but are not limited to, the human collagen I polyadenylation signal, the human collagen II polyadenylation signal, and the SV40 polyadenylation signal.

[0258] One or more vectors (e.g., expression vectors) containing nucleic acids encoding any of the antibodies (e.g., nucleic acids encoding the sequences listed in Table 3) can be introduced into suitable host cells for producing the antibodies. Non-limiting examples of host cells include Chinese hamster ovary (CHO) cells, dhfr-CHO cells, human embryonic kidney (HEK)-293 cells, Verda Reno (Vero) cells, non-secretory 0 (NS0) cells, human embryonic retina (PER.C6) cells, SP2 / 0 cells, baby hamster kidney (BHK) cells, Madin-Darby canine kidney (MDCK) cells, Madin-Darby bovine kidney (MDBK) cells, and monkey kidney CV1 line transformed with SV40 (COS) cells. In some embodiments, the host cells expressing the anti-CD22 antibody are CHO cells. The host cells can be cultured under conditions suitable for expression of the antibody or any polypeptide chain thereof. Such antibodies or polypeptide chains thereof can be recovered from cultured cells (e.g., from the cells or culture supernatant) by conventional methods, such as affinity purification. If necessary, the antibody polypeptide chains can be incubated under suitable conditions for a suitable period of time to allow for antibody production. In some embodiments, the host cell comprises nucleic acid encoding the heavy chain of the anti-CD22 antibody. In some embodiments, the host cell comprises nucleic acid encoding the light chain of the anti-CD22 antibody. In some embodiments, the host cell comprises nucleic acid encoding the heavy chain and nucleic acid encoding the light chain.

[0259] In some embodiments, the methods for preparing the antibodies described herein include a recombinant expression vector encoding both the heavy and light chains of an anti-CD22 antibody, as also described herein. The recombinant expression vector can be introduced into suitable host cells (e.g., dhfr-CHO cells) by conventional methods, such as calcium phosphate-mediated transfection. Positively transformant host cells can be selected and cultured under suitable conditions to allow expression of the two polypeptide chains that form the antibody, which can be recovered from the cells or culture medium. Optionally, the two chains recovered from the host cells can be incubated under suitable conditions to allow antibody formation.

[0260] In one example, two recombinant expression vectors are provided, one encoding the heavy chain of an anti-CD22 antibody and the other encoding the light chain of an anti-CD22 antibody, and both recombinant expression vectors can be introduced into suitable host cells (e.g., dhfr-CHO cells) by conventional methods, such as calcium phosphate-mediated transfection.

[0261] Alternatively, each expression vector can be introduced into a suitable host cell. Positive transformants can be selected and cultured under suitable conditions that allow for the expression of the antibody polypeptide chains. When two expression vectors are introduced into the same host cell, the antibody produced therein can be recovered from the host cell or culture medium. If necessary, the polypeptide chains can be recovered from the host cell or culture medium and then incubated under suitable conditions that allow for antibody formation. When two expression vectors are introduced into different host cells, each can be recovered from the corresponding host cell or the corresponding culture medium. The two polypeptide chains can then be incubated under conditions that allow for antibody formation.

[0262] Standard molecular biology techniques are used to prepare the recombinant expression vector, transfect the host cells, select for transformants, culture the host cells, and recover the antibody from the culture medium. For example, some antibodies can be isolated by affinity chromatography using a Protein A or Protein G coupled matrix.

[0263] Any of the nucleic acids encoding the heavy chain, light chain, or both of the anti-CD22 antibodies described herein (e.g., as provided in Table 3), vectors (e.g., expression vectors) containing such, and host cells containing the vectors are within the scope of this disclosure.

[0264] [Table 7]

[0265] Table 8

[0266] Table 9

[0267] Table 10

[0268] Table 11

[0269] Table 12

[0270] In some embodiments, the disclosure provides an isolated nucleic acid comprising a sequence that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 13, 39, 41, 43, 59, 73, and 87. In some embodiments, the disclosure provides an isolated nucleic acid comprising a sequence that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 14, 40, 42, 44, 60, 74, and 88. In some embodiments, the disclosure provides isolated nucleic acids comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 13, 39, 41, 43, 59, 73, and 87; and isolated nucleic acids comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 14, 40, 42, 44, 60, 74, and 88.

[0271] In some embodiments, the disclosure provides an isolated nucleic acid comprising a sequence that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 15, 61, 75, and 89. In some embodiments, the disclosure provides an isolated nucleic acid comprising a sequence that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 16, 62, 76, and 90. In some embodiments, the disclosure provides isolated nucleic acids comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 15, 61, 75, and 89; and nucleic acids comprising a sequence at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 16, 62, 76, and 90.

[0272] In some embodiments, the disclosure provides expression vectors encoding the anti-CD22 antibodies described herein. In some embodiments, the expression vector comprises an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 13, 39, 41, 43, 59, 73 and 87. In some embodiments, the expression vector comprises an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 14, 40, 42, 44, 60, 74 and 88. In some embodiments, the expression vector comprises an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 13, 39, 41, 43, 59, 73, and 87, and an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 14, 40, 42, 44, 60, 74, and 88. In some embodiments, an expression vector comprises an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 15, 61, 75, and 89. In some embodiments, an expression vector comprises an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 16, 62, 76, and 90.In some embodiments, the expression vector comprises an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 15, 61, 75, and 89, and an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 16, 62, 76, and 90.

[0273] In some embodiments, an anti-CD22 antibody described herein is produced by expressing in a recombinant cell (i) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 13, 39, 41, 43, 59, 73, and 87, and / or (ii) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 14, 40, 42, 44, 60, 74, and 88.

[0274] In some embodiments, an anti-CD22 antibody described herein is produced by expressing in a recombinant cell (i) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 15, 61, 75, and 89, and / or (ii) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 16, 62, 76, and 90.

[0275] In some embodiments, an anti-CD22 antibody described herein is produced by expressing in a recombinant cell an expression vector comprising: (i) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 13, 39, 41, 43, 59, 73, and 87; and / or (ii) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 14, 40, 42, 44, 60, 74, and 88.

[0276] In some embodiments, the anti-CD22 antibodies described herein are produced by expressing in a recombinant cell an expression vector comprising: (i) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 15, 61, 75, and 89; and / or (ii) an isolated nucleic acid that is at least 60% (e.g., 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%) identical to any one of SEQ ID NOs: 16, 62, 76, and 90.

[0277] In some embodiments, the present disclosure provides recombinant cells that express the anti-CD22 antibodies described herein (eg, recombinant cells for producing the antibodies).

[0278] Thus, the present disclosure provides methods of producing an antibody, the method comprising culturing a recombinant cell under conditions suitable for expression of the antibody from an expression vector by the recombinant cell. The recombinant cell expressing the antibody may be cultured under any suitable conditions known in the art. In some embodiments, the method further comprises isolating the antibody from the culture medium in which the cells are cultured, using any suitable method known in the art.

[0279] IV. Pharmaceutical Compositions The antibodies described herein, as well as the encoding nucleic acids or nucleic acid sets, vectors containing such, or host cells containing the vectors, can be mixed with a pharmaceutically acceptable carrier (excipient) to form a pharmaceutical composition for use in treating the target disease. By "acceptable," it is meant that the carrier must be compatible with (preferably capable of stabilizing) the active ingredient(s) of the composition and not harmful to the subject being treated. Pharmaceutically acceptable excipients (carriers), including buffers, are well known in the art. See, for example, Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K.E. Hoover.

[0280] The anti-CD22 antibody-containing pharmaceutical compositions disclosed herein may further comprise a suitable buffer. A buffer is a weak acid or base used to maintain the pH of a solution near a selected value after the addition of another acid or base. In some examples, the buffers disclosed herein may be buffers that can maintain physiological pH despite changes in carbon dioxide concentration (produced by cellular respiration). Exemplary buffers include, but are not limited to, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer, Dulbecco's phosphate-buffered saline (DPBS) buffer, or phosphate-buffered saline (PBS) buffer. Such buffers may contain disodium hydrogen phosphate and sodium chloride or potassium dihydrogen phosphate and potassium chloride.

[0281] In some embodiments, the buffering agent in the pharmaceutical compositions described herein may maintain a pH value of about 5 to 8. For example, the pH of the pharmaceutical composition may be about 7.1, 7.2, 7.3, 7.4, 7.5, 7.6, 7.7, 7.8, 7.9, or 8.0. In other examples, the pharmaceutical composition may have a pH value below 7, such as about 7, 6.8, 6.5, 6.3, 6, 5.8, 5.5, 5.3, or 5.

[0282] The pharmaceutical compositions described herein contain one or more suitable salts. Salts are ionic compounds that can be formed by the neutralization reaction of an acid and a base. (Skoog, DA; West, DM; Holler, JF; Crouch, SR (2004). "Chapters 14-16" Fundamentals of Analytical Chemistry (8th ed.)). Salts are composed of a relative number of cations (positively charged ions) and anions (negative ions) such that the product is electrically neutral (no net charge).

[0283] In some embodiments, the pharmaceutical composition may include a pharmaceutically acceptable carrier, excipient, or stabilizer in the form of a lyophilized formulation or an aqueous solution. (Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, Ed. K.E. Hoover). In some embodiments, the pharmaceutical composition may be formulated for intravenous injection. In some embodiments, the pharmaceutical composition may be formulated for subcutaneous injection.

[0284] Pharmaceutical compositions to be used for in vivo administration must be sterile. This is readily accomplished, for example, by filtration through sterile filtration membranes. Therapeutic antibody compositions are generally filled into a container having a sterile access port, such as an intravenous or hypodermic solution bag or a vial having a stopper pierceable by a hypodermic injection needle.

[0285] V. Method of Use Aspects of the present disclosure relate to compositions and methods for treating B cell disorders and / or one or more conditions resulting from B cell disorders in a subject.

[0286] In some aspects, the present disclosure features a method of treating a B cell disorder, the method including administering to a subject having the B cell disorder an effective amount of a therapeutic agent, thereby treating the B cell disorder, wherein the therapeutic agent is (i) any one or more of the antibodies or antigen-binding fragments thereof described herein (including conjugates), (ii) any one or more of the fusion proteins described herein, (iii) any one or more of the bispecific or multispecific polypeptides described herein, (iv) any one or more of the nucleic acids described herein, (v) any one or more of the expression vectors described herein, (vi) any one or more of the recombinant cells described herein, (vii) any one or more of the isolated polypeptides described herein, and / or (viii) any one or more of the pharmaceutical compositions described herein or includes them.

[0287] In some embodiments, the B cell disorder is an autoimmune disease, for example, the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), myasthenia gravis, Graves' disease or immune thrombocytopenic purpura (ITP).

[0288] In some embodiments, the B cell disorder is cancer. The cancer can be, for example, a B cell lymphoma such as non-Hodgkin lymphoma. Non-Hodgkin lymphoma can be, for example, Burkitt lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma, follicular lymphoma or mantle cell lymphoma.

[0289] In yet another aspect, the disclosure features a method of preventing, reducing, slowing, or inhibiting the proliferation and / or growth of cancer cells, comprising contacting the cancer cells with a therapeutic agent that binds to CD22 expressed on the surface of the cancer cells, where the therapeutic agent is (i) any one or more of the antibodies or antigen-binding fragments thereof (including conjugates) described herein, (ii) any one or more fusion proteins described herein, (iii) any one or more bispecific or multispecific polypeptides described herein, (iv) any one or more recombinant cells described herein, (v) any one or more isolated polypeptides described herein, and / or (vi) any one or more pharmaceutical compositions described herein.

[0290] In certain embodiments, the therapeutic agent may be administered by injection via intravenous, intraperitoneal, intracerebral (intraparenchymal), intraventricular, intramuscular, subcutaneous, intraocular, intraarterial, intracentral, or intrathecal routes, by sustained release system, or implantation device, hi certain embodiments, the composition may be administered by bolus injection, or continuously by infusion, or by implantable device.

[0291] Determining whether the amount of antibody (e.g., anti-CD22 antibody) achieves a therapeutic effect will be apparent to one of skill in the art based on the teachings provided herein. The effective amount, as recognized by those skilled in the art, will vary depending on factors within the knowledge and expertise of the medical practitioner, such as the particular condition being treated, the severity of the condition, individual patient parameters including age, physical condition, size, sex, and weight, duration of treatment, the nature of concurrent treatment (if any), the particular route of administration, and the like. The particular administration regimen used in the methods described herein, i.e., dosage, timing, and recurrence, will depend on the particular subject and the subject's medical history, as discussed herein.

[0292] Empirical considerations such as time to maximum effect, half-life, and / or time above a particular concentration generally contribute to determining the dosage. For example, antibodies compatible with the human immune system, such as humanized or fully human antibodies, can be used to extend the antibody's half-life and prevent it from being attacked by the host's immune system. Other reasons for dose adjustment include differences in pharmacokinetic or pharmacodynamic responses driven by gender, age, individual response, polymorphisms on the antibody target, and / or receptors involved in antibody clearance. Dosage frequency can be determined and adjusted over the course of treatment and is generally, but not necessarily, determined based on the treatment and / or suppression and / or improvement and / or delay of the target disease / disorder. Alternatively, sustained-release formulations of antibodies may be appropriate. Various formulations and devices for achieving sustained release are known in the art.

[0293] The administration frequency can vary according to the claimed methods. In some embodiments, the composition can be administered once. In some embodiments, the composition is administered on multiple occasions. In some embodiments, the administration frequency is weekly, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, every 8 weeks, every 9 weeks, or every 10 weeks, or once a month, every 2 months, or every 3 months or more. In some embodiments, the composition is administered daily, every other week, every other month, every month, or at any time interval that provides suitable (e.g., maximal) efficacy while minimizing safety risks to the subject. Generally, efficacy and therapeutic and safety risks can be monitored throughout the course of treatment.

[0294] In some embodiments, a subject may be administered a composition provided herein (e.g., an anti-CD22 antibody) at one or more intervals over a set period of time. In some cases, the periods during which a subject is administered a composition at one or more intervals may be separated by periods during which the subject is not administered a composition. In some embodiments, the relative duration of each period may depend on the subject's response to treatment or the severity of the disease, or both, and / or may be determined based on the judgment of the treating physician.

[0295] In some embodiments, the antibody can be administered parenterally. For example, parenteral compositions can be administered subcutaneously, intradermally, intravenously, intraperitoneally, intratumorally, intramuscularly, intraarticularly, intraarterially, or by infusion techniques. In addition, the antibody can be administered to a subject via an injectable depot administration route, such as using a one-month, three-month, or six-month depot injectable or biodegradable material and method.

[0296] In some embodiments, the antibody (e.g., anti-CD22 antibody) is administered intravenously. In some embodiments, the antibody (e.g., anti-CD22 antibody) is administered subcutaneously.

[0297] For intravenous injection, water-soluble antibodies can be administered by infusion, whereby a pharmaceutical formulation containing the antibody and a physiologically acceptable excipient is infused. Physiologically acceptable excipients may include, for example, 5% dextrose, 0.9% saline, Ringer's solution, or other suitable excipients. Other injectable compositions may contain various carriers, such as vegetable oils, dimethyl lactamide, dimethylformamide, ethyl lactate, ethyl carbonate, isopropyl myristate, ethanol, and polyols (glycerol, propylene glycol, liquid polyethylene glycol, etc.). In some cases, preparations, such as a sterile formulation of a suitable soluble salt form of the antibody, can be dissolved in a pharmaceutical excipient such as water for injection, 0.9% saline, or 5% glucose solution and administered.

[0298] In one embodiment, the antibody is administered via a site-specific or targeted local delivery technique. Examples of site-specific or targeted local delivery techniques include various implantable depot sources of antibody or local delivery catheters, such as infusion catheters, indwelling or needle catheters, synthetic grafts, adventitial wraps, shunts and stents or other implantable devices, site-specific carriers, direct injection, or direct administration. See, e.g., PCT Publication WO 00 / 53211 and U.S. Patent No. 5,981,568.

[0299] In some embodiments, a combination of two or more antibodies or an antibody and another suitable therapeutic agent may be administered to a subject in need of treatment. Antibodies may also be used in combination with other agents that serve to enhance and / or complement the effectiveness of the agent. The effectiveness of the treatment for the target disease / disorder may be assessed by methods well known in the art.

[0300] Anti-CD22 antibodies and therapeutic methods, including those described in this disclosure, can be used in combination with other types of treatment for the target disease or disorder disclosed herein. In this regard, the antibody compositions and therapeutic agents can be administered either simultaneously or sequentially. Examples include chemotherapy, immunotherapy, surgery, radiation therapy, gene therapy, etc., or anti-infective therapy. Such therapies can be administered simultaneously or sequentially (in any order) with the treatments according to this disclosure.

[0301] For example, a combination therapy can include an anti-CD22 antibody and pharmaceutical composition described herein co-formulated and / or co-administered with at least one additional therapeutic agent. Such combination therapy can advantageously utilize lower doses of the administered therapeutic agent, thus preventing potential toxicities or complications associated with various monotherapies.

[0302] In some embodiments, the antibodies described herein are directly or indirectly conjugated to one or more molecular payloads or labels. For example, in some embodiments, the antibodies described herein are conjugated to a molecular payload, e.g., a molecular payload that provides a therapeutic benefit to a subject, e.g., an antibody-drug conjugate (ADC). Thus, in some embodiments, a method for delivering a molecular payload to a subject for therapeutic purposes is provided. In such embodiments, the molecular payload can be a small molecule, a protein, a nucleic acid, an oligonucleotide, or any molecular entity that can modulate the activity or function of, for example, a gene, protein, and / or nucleic acid in a cell. In some embodiments, the molecular payload is a cytotoxic or chemotherapeutic agent.

[0303] Any of the anti-CD22 antibodies disclosed herein can be used to detect the presence of CD22 in vitro or in vivo. Results obtained from such detection methods can be used for diagnostic purposes (e.g., diagnosing a CD22-associated disease) or scientific research purposes (e.g., identifying new CD22-secreting cell types, studying the biological activity and / or regulation of secreted CD22). For assay uses, such as diagnostic uses, the anti-CD22 antibodies described herein can be conjugated to a detectable label (e.g., an imaging agent such as a contrast agent) to detect the presence of CD22 (e.g., soluble CD22) either in vivo or in vitro.

[0304] In other embodiments, the anti-CD22 antibodies described herein can be linked to a detectable label, which is a compound capable of emitting a detectable signal, either directly or indirectly, so that the aptamer can be detected, measured, and / or qualified in vitro or in vivo. Examples of such "detectable labels" are intended to include, but are not limited to, fluorescent labels, chemiluminescent labels, colorimetric labels, enzymatic markers, radioisotopes, and affinity tags such as biotin. Such labels can be conjugated directly or indirectly to the aptamer by conventional methods.

[0305] In some embodiments, the detectable label is an agent suitable for detecting CD22-expressing cells in vitro, which may be a radioactive molecule, a radiopharmaceutical, or an iron oxide particle. Suitable radioactive molecules for in vivo imaging include: 122 I, 123 I, 124 I, 125 I, 131 I, 18 F, 75 Br, 76 Br, 77 Br, 211 At, 225 Ac, 177 Lu, 153 Sm, 186 Re, 188 Re, 67 Cu, 213Bi, 212 Bi, 212 Pb and 67 Exemplary radiopharmaceuticals suitable for in vivo imaging include, but are not limited to, Ga. 111 Inoxyquinoline, 131 I sodium iodide, 99 mTc mebrofenin and 99 mTc red blood cells, 123 I sodium iodide, 99 mTc Examethadime, 99 mTc macroaggregated albumin, 99 mTc medronate, 99 mTc melithiazide, 99 mTc oxidronate, 99 mTc pentetate, 99 mTc pertechnetate, 99 mTc sestamibi, 99 mTc sulfur colloid, 99 Examples include mTc tetrofosmin, thallium-201, or xenon-133.

[0306] The reporting agent can also be a dye, such as a fluorophore, useful for detecting diseases mediated by CD22-expressing cells in tissue samples.

[0307] To perform a diagnostic assay in vitro, an anti-CD22 antibody can be contacted with a sample suspected of containing CD22, such as CD22-expressing cells in a disease microenvironment. The antibody and the sample can be incubated under suitable conditions for a suitable period of time to allow the antibody to bind to the CD22 antigen. Such an interaction can then be detected by conventional methods, such as ELISA, histological staining, or FACS. To perform a diagnostic assay in vivo, a suitable amount of an anti-CD22 antibody conjugated with a label (e.g., an imaging or contrast agent) can be administered to a subject requiring examination. The presence of the labeled antibody can be detected based on the signal emitted from the label by conventional methods.

[0308] Scientific research assays can be performed using anti-CD22 antibodies to test the biological activity of CD22, detect the presence of intracellular CD22, or modulate the effects of CD22. For example, a suitable amount of anti-CD22 can be contacted with a sample suspected of producing CD22 (e.g., a new cell type not previously identified as a CD22-producing cell). The cells are permeabilized before contacting with the anti-CD22 antibody. The antibody and sample can be incubated under suitable conditions for a suitable period of time to allow binding of the antibody to the CD22 antigen. Such interactions can then be detected via routine methods, such as ELISA, histological staining, or FACS.

[0309] VI. KITS FOR THERAPEUTIC AND DIAGNOSTIC USE The present disclosure also provides kits for the therapeutic or diagnostic uses disclosed herein. Such kits can include one or more containers containing an anti-CD22 antibody, such as any of those described herein.

[0310] In some embodiments, the kit may include instructions for use according to any of the methods described herein. The included instructions may include instructions for administering an anti-CD22 antibody to treat, delay the onset of, or alleviate a target disease as described herein. The kit may further include instructions for selecting an individual suitable for treatment based on identifying whether the individual has the target disease. In yet other embodiments, the instructions include instructions for administering the antibody to an individual at risk for the target disease.

[0311] Instructions for use of the anti-CD22 antibody generally include information regarding the dosage, administration schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages), or sub-unit doses. The instructions provided in the kits of the invention are typically written instructions on a label or package insert (e.g., a paper sheet included with the kit), although machine-readable instructions (e.g., instructions embodied on a magnetic or optical storage disk) are also acceptable.

[0312] The label or package insert indicates that the composition is used for treating, delaying the onset of, and / or ameliorating the disease or disorder. Instructions for practicing any of the methods described herein can be provided.

[0313] The kits of the present invention are in suitable packaging, including, but not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like.

[0314] Packages for use in combination with specific devices, such as infusion devices such as minipumps, are also contemplated. The kit may have a sterile access port (e.g., the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic needle). The container may also have a sterile access port (e.g., the container may be an intravenous solution bag or a vial having a stopper pierceable by a hypodermic needle). At least one active agent in the composition is an anti-CD22 antibody, such as those described herein.

[0315] Kits may optionally provide additional components, such as buffers and interpretive information. Typically, kits include a container and a label or package insert on or associated with the container. In some embodiments, the invention provides articles of manufacture comprising the contents of the kits described above.

[0316] Also provided herein are kits for use in detecting CD22 in a sample. Such kits may include any of the anti-CD22 antibodies described herein. In some examples, the anti-CD22 antibody may be conjugated to a detectable label as described herein. Conjugation or binding may include covalent or non-covalent bonds, as well as other forms of association, such as one entity on or within the other, or one or both entities on or within a third entity, such as a micelle.

[0317] Alternatively, or in addition, the kit may include a secondary antibody capable of binding to the anti-CD22 antibody. The kit may further include instructions for using the anti-CD22 antibody to detect CD22. [Example]

[0318] Example 1: Screening Methods SPRi for binding affinity Antibody binding kinetics experiments were performed using a Carterra® LSA with a pH 7.40 phosphate-buffered saline (PBS)-based running buffer and 1% BSA and 0.05% Tween 20. Antibodies were captured on an anti-human Fc capture chip prepared with an HC30M chip (Cartera). For kinetic analysis, purified recombinant His-tagged human CD22 was injected sequentially at concentrations ranging from 0.076 nM to 500 nM (serial 3-fold dilutions). For each concentration, there was a 5-minute association period followed by a 15-minute dissociation period. Results were processed and analyzed using Carterra LSA kinetics software. Sensorgrams showing the detector response versus time for the interaction between mAbs-1–4 and immobilized recombinant human CD22 are shown in Figures 1A–1D.

[0319] The output from the instrument is a sensorgram, which is a plot of detector response (measured in "resonance units" (RU)) as a function of time. An increase of 1000 RU corresponds to approximately 1 ng / mm of mass on the sensor surface. 2 Corresponding to the increase in

[0320] The kinetic data were referenced to an intervening reference spot, double-referenced to buffer cycles, and then globally fitted to a 1:1 binding model to determine apparent association and dissociation rate constants (ka and kd values). The ratio kd / ka was used to derive a KD value for each antigen / mab interaction, i.e., KD = kd / ka.

[0321] A summary of the binding kinetics of mAbs-1 to 4 is provided in Table 4 below.

[0322] [Table 13]

[0323] "Rmax" is the maximum SPR signal generated by mAbs-1-4 / CD22 interaction. "Res SD" refers to the residual standard deviation.

[0324] For the reactivity assay against rhesus CD22, 300 nM of His-tagged rhesus CD22 (Acro) was used in the binding assay. Results were processed and analyzed using Carterra LSA kinetics software (as described above). Data were referenced to an intercepted reference spot, double-referenced to buffer cycles, and then the response (nm) after association was reported. An isotype control was used to determine the cutoff response for positive binding. Under these conditions, mAb-1 was determined to be cross-reactive with rhesus CD22.

[0325] ii.Cell binding To calculate the EC50 for antibody binding to cells expressing CD22, anti-CD22 antibodies were tested at concentrations ranging from 100 nM to 0.6 pM (serial 3-fold dilutions) for binding to Raji cells. Cells were then incubated with the secondary antibody R-Phycoerythrin AfinIPure goat anti-human IgG (Jackson Immunoresearch 109-115-098). Data were acquired using a FACSCanto II (BD). Mean fluorescence intensity (MFI) was plotted against the concentration of anti-CD22 antibody. EC50 values ​​were derived from fitting a four-parameter dose-response curve.

[0326] A summary of the EC50 values ​​of mAbs-2 to 4 is shown in Table 5 below.

[0327] [Table 14]

[0328] Other embodiments All of the features disclosed herein may be combined in any combination. Each feature disclosed herein may be replaced by an alternative feature serving the same, equivalent, or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed herein is only an example of a generic series of equivalent or similar features.

[0329] From the above description, those skilled in the art can easily ascertain the essential features of the present invention, and can make various changes and modifications to the present invention to adapt it to various applications and conditions without departing from the spirit and scope thereof. Therefore, other embodiments are also described below.

[0330] Equivalents and Scope In the claims, articles such as "a," "an," and "the" may mean one or more unless stated to the contrary or otherwise clear from context. A claim or description including "or" between one or more members of a group is deemed to be satisfied when one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process, unless stated to the contrary or the context clearly dictates otherwise. The invention includes embodiments in which one member of a group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which two or more or all group members are present in, employed in, or otherwise relevant to a given product or process.

[0331] Furthermore, the present invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more enumerated claims are introduced into another claim. For example, any claim that depends on another claim can be modified to include one or more limitations found in any other claim that depends from the same base claim. Where elements are presented as lists, e.g., in Markush group format, each subgroup of elements is also disclosed, and any element can be removed from the group. In general, when the invention or aspects of the invention are referred to as including certain elements and / or features, it is to be understood that particular embodiments of the invention or particular aspects of the invention consist of or consist essentially of such elements and / or features. For the sake of brevity, these embodiments are not specifically described herein.

[0332] As used in this specification and claims, the term "and / or" should be understood to mean "either or both" of conjunctively combined elements, i.e., elements that are presented conjunctively in some cases and disjunctively in other cases. Multiple elements listed with "and / or" should be construed in the same manner, i.e., "one or more" of the elements so combined. Other elements other than the elements specifically identified by the "and / or" clause may optionally be present, whether related to the elements specifically identified or not. Thus, as a non-limiting example, a reference to "A and / or B," when used in conjunction with open language such as "comprising," may refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements), etc.

[0333] As used in this specification and claims, "or" should be understood to have the same meaning as "and / or" as defined above. For example, when separating items in a list, "or" or "and / or" shall be construed as inclusive, i.e., including at least one of a number or list of elements, but also including more than one, and optionally including additional unlisted items. Clearly indicated terms such as "only one" or "exactly one," or, when used in the claims, "consisting of," only refer to the inclusion of one element of a number or list of elements. In general, the term "or" as used herein should be construed as indicating exclusive alternatives (i.e., "one or the other, but not both") only when preceded by terms of exclusion, such as "either," "one," "only one," or "exactly one." When used in the claims, "consisting essentially of" shall have its ordinary meaning as used in the field of patent law.

[0334] As used herein, the phrase "at least one" in the specification and claims with reference to a list of one or more elements should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of every element specifically listed in the list of elements, and not necessarily excluding any combination of elements in the list of elements. This definition also allows for the optional presence of elements other than those specifically identified in the list of elements to which the phrase "at least one" refers, whether related or unrelated to the elements specifically identified. Thus, as a non-limiting example, "at least one of A and B" (or, equivalently, "at least one of A or B" or, equivalently, "at least one of A and / or B") may, for example, in one embodiment, refer to at least one (optionally multiple) A's (optionally including elements other than B) in the absence of B; in another embodiment, it may refer to at least one (optionally multiple) B's (optionally including elements other than A) in the absence of A; and in yet another embodiment, it may refer to at least one (optionally multiple) A's and at least one (optionally multiple) B's (optionally including other elements).

[0335] It should also be understood that, unless expressly indicated to the contrary, for methods including multiple steps or acts claimed herein, the order of the method steps or acts is not necessarily limited to the order in which the method steps or acts are described.

[0336] In the claims and the foregoing specification, all transitional phrases, such as "comprise," "include," "hold," "have," "contain," "involve," "holding," and "consisting of," are to be understood as open-ended, i.e., meaning including, but not limited to. Only the transitional phrases "consisting of" and "consisting essentially of" shall be closed or semi-closed transitional phrases, respectively, as set forth in the U.S. Patent Office Manual of Patent Examining Procedure, Section 2111.03. It is understood that embodiments described herein using an open-ended transitional phrase (e.g., "comprising") are also contemplated in alternative embodiments as "consisting of" and "consisting essentially of" the feature described by the open-ended transitional phrase. For example, if the application describes a "composition comprising A and B," the application also contemplates the alternative embodiments "a composition consisting of A and B" and "a composition consisting essentially of A and B."

[0337] When ranges are stated, the endpoints are included. Furthermore, unless otherwise stated or otherwise clear from the context and the understanding of one of ordinary skill in the art, values ​​expressed as ranges can take any particular value or subrange within the stated range in different embodiments of the invention, down to one-tenth of the unit of the lower limit of that range, unless otherwise clearly indicated by the context.

[0338] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. In the event of a conflict between any of the incorporated references and this specification, this specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Such embodiments may be excluded even if the exclusion is not explicitly set forth herein, because they are deemed to be known to those of ordinary skill in the art. Any particular embodiment of the present invention may be excluded from a claim for any reason, whether related to the existence of prior art or not.

[0339] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments described herein. The scope of the embodiments described herein is not limited to the above description, but is as set forth in the appended claims. Those skilled in the art will appreciate that various changes and modifications can be made to the specification without departing from the spirit or scope of the invention, as defined in the following claims.

[0340] The reference to a list of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The listing of an embodiment for a variable herein includes this embodiment as any single embodiment or in combination with any other embodiment or portion thereof. The listing of an embodiment herein includes this embodiment as any single embodiment or in combination with any other embodiment or portion thereof.

Claims

1. An antibody that specifically binds to human CD22, comprising HC CDR1, HC CDR2 and HC CDR3 of a heavy chain variable region set forth in SEQ ID NO: 7, 55, 69 or 83.

2. 2. The isolated antibody of claim 1, further comprising LC CDR1, LC CDR2 and LC CDR3 of a light chain variable region set forth in SEQ ID NO: 8, 56, 70 or 84.

3. (i) (a) HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 1; (b) HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 2; and (c) HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO: 3; (ii) (a) HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:49; (b) HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:50; and (c) HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:51; (iii) (a) HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:63, (b) HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:64, and (c) HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:65; or (iv) The antibody of claim 1 or 2, wherein (a) the HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 63, (b) the HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 78, and (c) the HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:

79.

4. (i) (a) the LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:4; (b) the LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:5; and (c) the LC is or comprises the amino acid sequence set forth in SEQ ID NO:6; (ii) (a) the LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 52; (b) the LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 53; and (c) the LC is or comprises the amino acid sequence set forth in SEQ ID NO: 54; (iii) (a) LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 66; (b) LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 67; and (c) LC is or comprises the amino acid sequence set forth in SEQ ID NO: 68; or (iv) The antibody of claim 2 or 3, wherein (a) the LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 80, (b) the LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 81, and (c) the LC is or comprises the amino acid sequence set forth in SEQ ID NO:

82.

5. (i) (a) HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 1; (b) HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 2; (c) HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO: 3; (d) LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 4; (e) LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 5; and (f) LC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO: 6, (ii) (a) HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:49, (b) HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:50, (c) HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:51, (d) LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:52, (e) LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:53, and (f) LC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:54, (iii) (a) HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:63; (b) HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:64; (c) HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:65; (d) LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO:66; (e) LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO:67; and (f) LC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:68; or (iv) The antibody of any one of claims 1 to 4, wherein (a) the HC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 63, (b) the HC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 78, (c) the HC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO: 79, (d) the LC CDR1 is or comprises the amino acid sequence set forth in SEQ ID NO: 80, (e) the LC CDR2 is or comprises the amino acid sequence set forth in SEQ ID NO: 81, and (f) the LC CDR3 is or comprises the amino acid sequence set forth in SEQ ID NO:

82.

6. (i) a heavy chain variable region sequence set forth in SEQ ID NO: 7 and a light chain variable region sequence set forth in SEQ ID NO: 8; (ii) a heavy chain variable region sequence set forth in SEQ ID NO: 55 and a light chain variable region sequence set forth in SEQ ID NO: 56; (iii) a heavy chain variable region sequence set forth in SEQ ID NO: 69 and a light chain variable region sequence set forth in SEQ ID NO: 70; or (iv) a heavy chain variable region sequence set forth in SEQ ID NO: 83 and a light chain variable region sequence set forth in SEQ ID NO: 84 The antibody of any one of claims 1 to 5, comprising:

7. The antibody of any one of claims 1 to 5, comprising a heavy chain variable region comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 8, 56, 70 or 84.

8. The antibody of any one of claims 1 to 5 or 7, comprising a light chain variable region comprising an amino acid sequence that is at least 75%, 80%, 85%, 90%, 95%, 99% or 100% identical to the amino acid sequence of SEQ ID NO: 7, 55, 69 or 83.

9. An antibody that cross-competes with the antibody of any one of claims 1 to 8 for binding to human CD22.

10. The antibody according to any one of claims 1 to 9, which is a human antibody.

11. The antibody of any one of claims 1 to 10, comprising a heavy chain constant region.

12. The antibody of any one of claims 1 to 10, comprising a human heavy chain Fc region.

13. The antibody of claim 12, wherein the heavy chain Fc region is selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

14. The antibody of any one of claims 1 to 13, which is an IgG1 antibody.

15. An antibody according to any one of claims 1 to 14, comprising a light chain constant region.

16. 16. The antibody of claim 15, wherein the light chain is a kappa light chain.

17. The antibody of any one of claims 14 to 16, comprising a heavy chain set forth in SEQ ID NO: 11, 57, 71 or 85.

18. 18. The antibody of claim 16 or 17, comprising a light chain set forth in SEQ ID NO: 12, 58, 72 or 86.

19. (i) a heavy chain set forth in SEQ ID NO: 11 and a light chain set forth in SEQ ID NO: 12; (ii) a heavy chain set forth in SEQ ID NO: 57 and a light chain set forth in SEQ ID NO: 58; (iii) a heavy chain set forth in SEQ ID NO: 71 and a light chain set forth in SEQ ID NO: 72; or (iv) a heavy chain set forth in SEQ ID NO: 85 and a light chain set forth in SEQ ID NO: 86 The antibody of any one of claims 1 to 18, comprising:

20. The antibody of any one of claims 1 to 19, further comprising a heterologous moiety.

21. The antibody of any one of claims 1 to 20, wherein the heterologous moiety is a cytotoxic agent, a cytostatic agent, a radionuclide or a detectable label.

22. A fusion protein comprising the antibody of any one of claims 1 to 21.

23. The antibody of any one of claims 1 to 19, which is a multispecific antibody that specifically binds to CD22 and one or more further target antigens.

24. 24. The antibody of claim 23, which is a bispecific antibody that specifically binds to CD22 and one further target antigen.

25. An isolated nucleic acid encoding the antibody of any one of claims 1 to 19, 23 or 24 or the fusion protein of claim 22.

26. 26. An expression vector comprising the isolated nucleic acid of claim 25.

27. 27. A recombinant cell comprising the isolated nucleic acid of claim 25 or the expression vector of claim 26.

28. 27. A method of expressing an antibody according to any one of claims 1 to 19, 23 or 24 or a fusion protein according to claim 22, comprising culturing a recombinant cell or a plurality of said cells according to claim 27 under conditions suitable for expression of said antibody or said fusion protein from said expression vector by said one or more cells.

29. 29. The method of claim 28, further comprising isolating the antibody or fusion protein from the one or more cells or the culture medium in which the one or more cells were cultured.

30. 30. An isolated antibody or fusion protein produced by the method of claim 28 or 29.

31. (a) A composition comprising (i) an antibody of any one of claims 1 to 19, 23 or 24, (ii) a fusion protein of claim 22, (iii) an isolated nucleic acid of claim 25, (iv) an expression vector of claim 26, (v) a recombinant cell of claim 27, or (vi) an antibody or fusion protein of claim 30, and (b) a pharmaceutically acceptable carrier or excipient.

32. 32. A method of treating a B cell disorder, comprising administering to a subject having a B cell disorder an effective amount of a therapeutic agent, thereby treating the B cell disorder, wherein the therapeutic agent is or comprises: (i) an antibody of any one of claims 1 to 19, 23 or 24; (ii) a fusion protein of claim 22; (iii) an isolated nucleic acid of claim 25; (iv) an expression vector of claim 26; (v) a recombinant cell of claim 27; (vi) an antibody or fusion protein of claim 30; or (vii) a pharmaceutical composition of claim 31.

33. 33. The method of claim 32, wherein the B cell disorder is an autoimmune disease.

34. 34. The method of claim 33, wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), myasthenia gravis, Graves' disease, or immune thrombocytopenic purpura (ITP).

35. 33. The method of claim 32, wherein the B cell disorder is cancer.

36. 36. The method of claim 35, wherein the cancer is a B-cell lymphoma.

37. 37. The method of claim 36, wherein the B-cell lymphoma is non-Hodgkin's lymphoma.

38. 38. The method of claim 37, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma.

39. The method of any one of claims 32 to 38, wherein the therapeutic agent is administered intravenously.

40. The method of any one of claims 32 to 38, wherein the therapeutic agent is administered subcutaneously.

41. 1. An antibody that specifically binds to human CD22, comprising HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3; (i) (a) HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 1; (b) HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 2; and (c) HC (d) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 3; (e) LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 4; CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:5; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:6; (ii) (a) HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 49; (b) HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 50; and (c) HC (d) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 51; (e) LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 52; (f) LC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 53; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 54; (iii) (a) HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; (b) HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 64; and (c) HC (d) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 65; (e) LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 66; CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 67; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 68; or (iv) (a) HC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; (b) HC CDR2 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 78; and (c) HC (d) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 79; (e) LC CDR1 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 80; and (f) LC CDR3 comprises an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

82.

42. (i) VH is (a) an HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 1; (b) an HC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:2; or (c) a HC CDR3 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

3. and VL is, (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:4; (e) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 5; or (f) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

6. Contains or (ii) VH is (a) an HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 49; (b) an HC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 50; or (c) a HC CDR3 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

51. and VL is, (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 52; (e) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 53; or (f) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

54. Contains or (iii) VH is (a) an HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; (b) an HC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 64; or (c) a HC CDR3 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

65. and VL is, (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 66; (e) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 67; or (f) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

68. contains, or (iv) VH is (a) an HC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 63; (b) an HC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 78; or (c) a HC CDR3 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

79. and VL is, (d) an LC CDR1 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 80; (e) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO: 81; or (f) an LC CDR2 comprising an amino acid sequence having at least 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, 99.99% or 100% identity to SEQ ID NO:

82.

42. The antibody of claim 41, comprising:

43. (a) the V Ｈ comprises at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c); or (b) the V Ｌ comprises at least two CDRs selected from (i)(d)-(f), (ii)(d)-(f), (iii)(d)-(f), or (iv)(d)-(f); or (c) Said V Ｈ comprises at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c), and said V Ｌ The antibody of claim 41 or 42, comprising at least two CDRs selected from (i)(d)-(f), (ii)(d)-(f), (iii)(d)-(f), or (iv)(d)-(f).

44. An antibody that cross-competes with the antibody of any one of claims 41 to 43 for binding to human CD22.

45. The antibody of any one of claims 41 to 44, which is a human antibody.

46. An antibody according to any one of claims 41 to 45, comprising a heavy chain constant region.

47. The antibody of any one of claims 41 to 46, comprising a human heavy chain constant region.

48. The antibody of any one of claims 41 to 47, wherein the heavy chain constant region is selected from the group consisting of IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2.

49. The antibody of any one of claims 41 to 48, wherein the heavy chain constant region is IgG1.

50. The antibody of any one of claims 41 to 49, wherein the engineered antibody further comprises a heterologous moiety.

51. 51. The antibody of claim 50, wherein the heterologous moiety is a cytotoxic agent, a cytostatic agent, a radionuclide, or a detectable label.

52. A fusion protein comprising the antibody of any one of claims 41 to 51.

53. The antibody of any one of claims 41 to 52, which is a multispecific antibody that specifically binds to CD22 and one or more further target antigens.

54. 54. The antibody of claim 53, which is a bispecific antibody that specifically binds to CD22 and one additional target antigen.

55. An isolated nucleic acid encoding the antibody of any one of claims 41 to 49, 53 or 54 or the fusion protein of claim 52.

56. 56. An expression vector comprising the isolated nucleic acid of claim 55.

57. 57. A recombinant cell comprising the isolated nucleic acid of claim 55 or the expression vector of claim 56.

58. 55. A method of expressing an antibody of any one of claims 41 to 49, 53 or 54, comprising culturing a recombinant cell or a plurality of said cells of claim 57 under conditions suitable for expression of said polypeptide from said expression vector by said one or more cells.

59. 59. The method of claim 58, further comprising isolating the polypeptide from the one or more cells or the culture medium in which the one or more cells were cultured.

60. 60. An antibody or fusion protein produced by the method of claim 58 or 59.

61. 60. A pharmaceutical composition comprising: (a) (i) an antibody of any one of claims 41-49, 53, or 54; (ii) a fusion protein of claim 52; (iii) an isolated nucleic acid of claim 55; (iv) an expression vector of claim 56; (v) a recombinant cell of claim 57; or (vi) an isolated antibody or fusion protein of claim 60; and (b) a pharmaceutically acceptable carrier or excipient.

62. 62. A method of treating a B cell disorder, comprising administering to a subject having a B cell disorder an effective amount of a therapeutic agent, thereby treating the B cell disorder, wherein the therapeutic agent is or comprises: (i) an antibody of any one of claims 41-49, 53, 54 or 90; (ii) a fusion protein of claim 52; (iii) an isolated nucleic acid of claim 55; (iv) an expression vector of claim 56; (v) a recombinant cell of claim 57; (vi) an isolated antibody or fusion protein of claim 60; or (vii) a composition of claim 61.

63. 63. The method of claim 62, wherein the B cell disorder is an autoimmune disease.

64. 64. The method of claim 63, wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), myasthenia gravis, Graves' disease, or immune thrombocytopenic purpura (ITP).

65. 63. The method of claim 62, wherein the B cell disorder is cancer.

66. 66. The method of claim 65, wherein the cancer is a B-cell lymphoma.

67. 67. The method of claim 66, wherein the B-cell lymphoma is non-Hodgkin's lymphoma.

68. 68. The method of claim 67, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma.

69. 69. The method of any one of claims 62 to 68, wherein the therapeutic agent is administered intravenously.

70. 69. The method of any one of claims 62 to 68, wherein the therapeutic agent is administered subcutaneously.

71. A chimeric antigen receptor (CAR) comprising the antibody of any one of claims 1 to 8, 41 to 43, or 90.

72. The CAR of claim 71, further comprising a hinge region.

73. 73. The CAR of claim 71 or 72, further comprising a transmembrane domain.

74. The CAR according to any one of claims 71 to 73, further comprising an intracellular domain.

75. The CAR of any one of claims 71 to 74, further comprising a costimulatory domain.

76. An isolated nucleic acid encoding the CAR of any one of claims 71 to 75.

77. 77. An expression vector comprising the isolated nucleic acid of claim 76.

78. An immune cell that expresses the CAR of any one of claims 71 to 75, or comprises the isolated nucleic acid of claim 76 or the expression vector of claim 77.

79. The immune cell of claim 78, which is a T cell, an NK cell, or an NKT cell.

80. 80. A composition comprising the immune cells of claim 78 or 79 and a pharmaceutically acceptable carrier.

81. 81. A method of treating a B cell disorder, comprising administering to a subject with a B cell disorder an effective amount of an immune cell of claim 78 or 79 or a composition of claim 80.

82. 82. The method of claim 81, wherein the B cell disorder is an autoimmune disease.

83. 83. The method of claim 82, wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), myasthenia gravis, Graves' disease, or immune thrombocytopenic purpura (ITP).

84. 82. The method of claim 81, wherein the B cell disorder is cancer.

85. 85. The method of claim 84, wherein the cancer is a B-cell lymphoma.

86. 86. The method of claim 85, wherein the B-cell lymphoma is non-Hodgkin's lymphoma.

87. 87. The method of claim 86, wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma.

88. 88. The method of any one of claims 81 to 87, wherein the immune cells or the composition are administered intravenously.

89. 88. The method of any one of claims 81 to 87, wherein the immune cells or the composition are administered subcutaneously.

90. (i) the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 of any one of the antibodies listed in Table 1; (ii) the VH and / or VL of any one of the antibodies listed in Table 1; or (iii) the heavy and / or light chain of any one of the antibodies listed in Table 1 An antibody comprising:

91. ARELTGDAFDX ７ (SEQ ID NO: 35) (wherein X ７ wherein R is I or L).

92. GFX １ FX ２ X ３ YG (SEQ ID NO: 33) (wherein X １ is T or I, and X ２ is S or R, and X ３ is S or N) ４ X ５ X ６ (SEQ ID NO: 34) (wherein X ４ is N or S, and X ５ is K or N, and X ６ The antibody of claim 91, further comprising an HC CDR2 comprising the amino acid sequence:

93. QX ８ IGSX ９ (SEQ ID NO: 36) (wherein X ８ is S or R, and X ９ is S or H), LC CDR1 comprising the amino acid sequence of YAS, and / or LC CDR2 comprising the amino acid sequence of HQSSX １０ EPYT (SEQ ID NO: 38) (wherein X １０ 93. The antibody of claim 91 or 92, further comprising an LC CDR3 comprising the amino acid sequence:

94. GFX １ FX ２ X ３ YG (SEQ ID NO: 33) (wherein X １ is T or I, and X ２ is S or R, and X ３ is S or N) ４ X ５ X ６ (SEQ ID NO: 34) (wherein X ４ is N or S, and X ５ is K or N, and X ６ is K or N) ７ (SEQ ID NO: 35) (wherein X ７ QX is I or L) ８ IGSX ９ (SEQ ID NO: 36) (wherein X ８ is S or R, and X ９ is S or H), LC CDR1 comprising the amino acid sequence of YAS, and / or LC CDR2 comprising the amino acid sequence of HQSSX １０ EPYT (SEQ ID NO: 38) (wherein X １０ is T, R, or S).

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