Anti-CD22 antibodies and uses thereof

Abstract

Aspects of the present application provide anti-CD22 antibodies and methods of using these antibodies to treat subjects having a B-cell disorder.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

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

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

[0003] CD22 is a cell surface sialylated glycoprotein that is uniquely present on mature B lymphocytes but not on precursor B cells. CD22 modulates B cell function and proliferation. As B cells mature, expression of CD22 increases and localizes to the cell surface. Other cells such as lymphomas, leukemias, and lymphocytic B cells also produce CD22. CD22 has been associated with autoimmune disorders and B cell malignancies. SUMMARY

[0004] The present disclosure relates, among other things, to antibodies and antigen-binding fragments thereof that bind to CD22 (e.g., human CD22). For example, in one aspect, the present 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 a HC CDR3 comprising or consisting of the amino acid sequence depicted in SEQ ID NO: 3. In some embodiments, the present 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 a HC CDR3 comprising or consisting of the amino acid sequence depicted in SEQ ID NO: 51. In some embodiments, the present 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 a HC CDR3 comprising or consisting of the amino acid sequence depicted in SEQ ID NO: 65. In some embodiments, the present 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 a HC CDR3 comprising or consisting of the amino acid sequence depicted 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), wherein the antibody or antigen-binding fragment thereof comprises a HC CDR3 comprising or consisting of an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from 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), wherein the antibody or antigen-binding fragment thereof comprises a HC CDR3 comprising or consisting of an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from 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), wherein the antibody or antigen-binding fragment thereof comprises a HC CDR3 comprising or consisting of an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from 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 a HC CDR3 comprising or consisting of an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 79.

[0006] In another aspect, the present 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 the three CDRs of the heavy chain variable region depicted in SEQ ID NO: 7 (HC CDR1, HC CDR2, and HC CDR3). In some embodiments, the present 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 the three CDRs of the heavy chain variable region depicted in SEQ ID NO: 55 (HC CDR1, HC CDR2, and HC CDR3). In some embodiments, the present 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 the three CDRs of the heavy chain variable region depicted in SEQ ID NO: 69 (HC CDR1, HC CDR2, and HC CDR3). In some embodiments, the present 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 the three CDRs of the heavy chain variable region depicted in SEQ ID NO: 83 (HC CDR1, HC CDR2, and HC CDR3). In some embodiments, the CDRs are according to the Kabat definition. In some embodiments, the CDRs are according to the Chothia definition. In some embodiments, the CDRs are according to the IMGT definition.

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

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

[0009] In some embodiments, any of the antibodies or antigen-binding fragments thereof described herein comprise 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 of the antibodies or antigen-binding fragments thereof described herein comprise 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 of the antibodies or antigen-binding fragments thereof described herein comprise 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 of the antibodies or antigen-binding fragments thereof described herein comprise 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 according to the Chothia definition. In some embodiments, the CDRs are according to the IMGT definition.

[0010] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) HC CDR1 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 1, (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 2, and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 3; (ii) (a) HC CDR1 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 49, (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 50, and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 51; (iii) (a) HC CDR1 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 63, (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 64, and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 65; or (iv) (a) HC CDR1 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 63, (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 78, and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 79.

[0011] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) an HC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 1, (b) an HC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 2, and (c) an HC CDR3 that is or comprises an amino acid sequence that has 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 versus the amino acid sequence depicted in SEQ ID NO: 3; (ii) (a) an HC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 49, (b) an HC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 50, and (c) an HC CDR3 that is or comprises an amino acid sequence that has 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 versus the amino acid sequence depicted in SEQ ID NO: 51; (iii) (a) an HC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 63, (b) an HC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 64, and (c) an HC CDR3 that is or comprises an amino acid sequence that has 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 versus the amino acid sequence depicted in SEQ ID NO: 65; or (iv) (a) an HC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 63, (b) an HC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 78, and (c) an HC CDR3 that is or comprises an amino acid sequence that has 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 versus the amino acid sequence depicted in SEQ ID NO: 79.

[0012] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 1, (b) HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 2, and (c) HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 3; (ii) (a) HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 49, (b) HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 50, and (c) HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 51; (iii) (a) HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 63, (b) HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 64, and (c) HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 65;or (iv) (a) the HC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 63 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) the HC CDR2 is or comprises 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) the HC CDR3 is or comprises 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 features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) the LC CDR1 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) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 5, and (c) the LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 6; (ii) (a) the LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 52 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) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 53, and (c) the LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 54; (iii) (a) the LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 66 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) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 67, and (c) the LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 68; or (iv) (a) the LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 80 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) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 81, and (c) the LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 82.

[0014] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 4, (b) LC CDR2 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 5, and (c) LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 6; (ii) (a) LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 52, (b) LC CDR2 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 53, and (c) LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 54; (iii) (a) LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 66, (b) LC CDR2 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 67, and (c) LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 68; or (iv) (a) LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 80, (b) LC CDR2 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 81, and (c) LC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 82.

[0015] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) the LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 4, (b) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 5, and (c) the LC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 6; (ii) (a) the LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 52, (b) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 53, and (c) the LC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 54; (iii) (a) the LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 66, (b) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 67, and (c) the LC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 68; or (iv) (a) the LC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 80, (b) the LC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 81, and (c) the LC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 82.

[0016] In another aspect, the disclosure features an isolated antibody or antigen-binding fragment thereof that comprises: (i) (a) LC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 4, (b) LC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 5, and (c) LC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 6; (ii) (a) LC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 52, (b) LC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 53, and (c) LC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 54; (iii) (a) LC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 66, (b) LC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 67, and (c) LC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 68;or (iv) (a) LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 80 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 81 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (c) LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 82 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions.

[0017] In yet another aspect, the disclosure features an isolated antibody or antigen- binding fragment thereof that comprises: (i) (a) HC CDR1 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 1, (b) HC CDR2 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 2, (c) HC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 3, (d) LC CDR1 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 4, (e) LC CDR2 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 5, and (f) LC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 6.(ii) (a) HC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 49 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) HC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 50 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (c) HC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 51 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (d) LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 52 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (e) LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 53 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (f) LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 54 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions; (iii) (a) HC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 63 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (b) HC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 64 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (c) HC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 65 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (d) LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 66 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, (e) LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 67 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions, and (f) LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 68 by not more than four (e.g., not more than three, not more than two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions;or (iv) (a) the HC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 63 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) the HC CDR2 is or comprises 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, (c) the HC CDR3 is or comprises 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, (d) the LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 80 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, (e) the LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 81 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 (f) the LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 82 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. LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 81 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 (f) the LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 82 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.

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

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

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

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

[0022] In some embodiments, the isolated antibody or antigen binding fragment thereof described herein comprises: (i) (a) LC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 4, (b) LC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 5, and (c) LC CDR3 that is or comprises the amino acid sequence depicted in SEQ ID NO: 6; (ii) (a) LC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 52, (b) LC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 53, and (c) LC CDR3 that is or comprises the amino acid sequence depicted in SEQ ID NO: 54; (iii) (a) LC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 66, (b) LC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 67, and (c) LC CDR3 that is or comprises the amino acid sequence depicted in SEQ ID NO: 68; or (iv) (a) LC CDR1 that is or comprises the amino acid sequence depicted in SEQ ID NO: 80, (b) LC CDR2 that is or comprises the amino acid sequence depicted in SEQ ID NO: 81, and (c) LC CDR3 that is or comprises the amino acid sequence depicted 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 depicted in SEQ ID NO: 1, (b) an HC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 2, (c) an HC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 3, (d) an LC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 4, (e) an LC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 5, and (f) an LC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 6; (ii) (a) an HC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 49, (b) an HC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 50, (c) an HC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 51, (d) an LC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 52, (e) an LC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 53, and (f) an LC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 54; (iii) (a) an HC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 63, (b) an HC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 64, (c) an HC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 65, (d) an LC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 66, (e) an LC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 67, and (f) an LC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 68; or (iv) (a) an HC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 63, (b) an HC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 78, (c) an HC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 79, (d) an LC CDR1 comprising the amino acid sequence depicted in SEQ ID NO: 80, (e) an LC CDR2 comprising the amino acid sequence depicted in SEQ ID NO: 81, and (f) an LC CDR3 comprising the amino acid sequence depicted in SEQ ID NO: 82.

[0024] In some embodiments, the isolated antibody or antigen-binding fragment thereof comprises (i) a heavy chain variable region sequence set forth in SEQ ID NO: 7 and / or 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 / or 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 / or 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 / or a 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 that is at least 75% (e.g., at least 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 isolated antibody or antigen-binding fragment thereof described herein can comprise a heavy chain variable region comprising: (i) (a) the HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 1, (b) the HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 2, and (c) the HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 3, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 7; (ii) (a) the HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 49, (b) the HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 50, and (c) the HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 51, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 55;(iii) (a) HC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 63 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) HC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 64 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) HC CDR3 is or comprises 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, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 69; or (iv) (a) HC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 63 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) HC CDR2 is or comprises 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) HC CDR3 is or comprises 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, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 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 can comprise a heavy chain variable region comprising: (a) HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 1; (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 2; and (c) HC CDR3 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, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 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 can comprise a heavy chain variable region comprising: (a) the HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 49; (b) the HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 50; and (c) the HC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 51, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 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 can comprise a heavy chain variable region comprising: (a) the HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 63; (b) the HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 64; and (c) the HC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 65, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 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 can comprise a heavy chain variable region comprising: (a) the HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 63; (b) the HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 78; and (c) the HC CDR3 is or comprises an amino acid sequence that differs by no more than four (e.g., no more than three, two, or one) amino acid substitutions (e.g., conservative substitutions), deletions, or insertions from SEQ ID NO: 79, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 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 heavy chain variable region comprising an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 7, 71, or 85. Thus, for example, in some embodiments, the isolated antibody or antigen-binding fragment thereof described herein can comprise a heavy chain variable region comprising: (i) (a) HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 1, (b) HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 2, and (c) HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 3, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 7; (ii) (a) HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 49, (b) HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 50, and (c) HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 51, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 71; or (iii) (a) HC CDR1 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 45, (b) HC CDR2 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 46, and (c) HC CDR3 is or comprises an amino acid sequence that differs 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 from SEQ ID NO: 47, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 85.(iii) (a) LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 66 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) LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 67 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) LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 68 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, wherein the light chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 70; or (iv) (a) LC CDR1 is or comprises an amino acid sequence that differs from SEQ ID NO: 80 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) LC CDR2 is or comprises an amino acid sequence that differs from SEQ ID NO: 81 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) LC CDR3 is or comprises an amino acid sequence that differs from SEQ ID NO: 82 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, wherein the light chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 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 can comprise a heavy chain variable region comprising: (a) HC CDR1 is or comprises an amino acid sequence depicted in SEQ ID NO: 1; (b) HC CDR2 is or comprises an amino acid sequence depicted in SEQ ID NO: 2; and (c) HC CDR3 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, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 7.

[0032] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein can comprise a heavy chain variable region comprising: (a) HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 1; (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 2; and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 3, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 5.

[0033] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein can comprise a heavy chain variable region comprising: (a) HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 15; (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 16; and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 17, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 19.

[0034] In some embodiments, an isolated antibody or antigen-binding fragment thereof described herein can comprise a heavy chain variable region comprising: (a) HC CDR1 is or comprises the amino acid sequence depicted in SEQ ID NO: 29; (b) HC CDR2 is or comprises the amino acid sequence depicted in SEQ ID NO: 30; and (c) HC CDR3 is or comprises the amino acid sequence depicted in SEQ ID NO: 31, wherein the heavy chain variable region comprises an amino acid sequence that is at least 75% (e.g., at least 80%, 85%, 90%, 95%, 99%, or 100%) identical to the amino acid sequence of SEQ ID NO: 33.

[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 that is 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% identical to SEQ ID NO: 1, (b) the HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 2, (c) the HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 3, (d) the LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 4, (e) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 5, and (f) the LC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 6; (ii) (a) the HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 49, (b) the HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 50, (c) the HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 51, (d) the LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 52, (e) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 53, and (f) the LC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 54.99.99% or 100% identical to SEQ ID NO: 52, (e) LC CDR2 comprises an amino acid sequence 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% identical to SEQ ID NO: 53, and (f) LC CDR3 comprises an amino acid sequence 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% identical to SEQ ID NO: 54; (iii) (a) HC CDR1 comprises an amino acid sequence 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% identical to SEQ ID NO: 63, (b) HC CDR2 comprises an amino acid sequence 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% identical to SEQ ID NO: 64, (c) HC CDR3 comprises an amino acid sequence 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% identical to SEQ ID NO: 65, (d) LC CDR1 comprises an amino acid sequence 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% identical to SEQ ID NO: 66, (e) LC CDR2 comprises an amino acid sequence 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% identical to SEQ ID NO: 67, and (f) LC CDR3 comprises an amino acid sequence 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% identical to SEQ ID NO: 68.an amino acid sequence 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% identical to SEQ ID NO: 68; or (iv) (a) the HC CDR1 comprises an amino acid sequence 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% identical to SEQ ID NO: 63, (b) the HC CDR2 comprises an amino acid sequence 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% identical to SEQ ID NO: 78, (c) the HC CDR3 comprises an amino acid sequence 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% identical to SEQ ID NO: 79, (d) the LC CDR1 comprises an amino acid sequence 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% identical to SEQ ID NO: 80, (e) the LC CDR2 comprises an amino acid sequence 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% identical to SEQ ID NO: 81, and (f) the LC CDR3 comprises an amino acid sequence 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% identical to SEQ ID NO: 82.

[0036] In some embodiments, the anti-CD22 antibody comprises: (i) a heavy chain variable domain (V H ) comprising: (a) a HC CDR1 comprising an amino acid sequence that is 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% identical to SEQ ID NO: 1, (b) a HC CDR2 comprising an amino acid sequence that is 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% identical to SEQ ID NO: 2, and (c) a HC CDR3 comprising an amino acid sequence that is 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% identical to SEQ ID NO: 3; and a light chain variable domain (V L ) comprising: (d) a LC CDR1 comprising an amino acid sequence that is 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% identical to SEQ ID NO: 4, (e) a LC CDR2 comprising an amino acid sequence that is 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% identical to SEQ ID NO: 5, and (f) a LC CDR3 comprising an amino acid sequence that is 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% identical to SEQ ID NO: 6; (ii) a heavy chain variable domain (V H): (a) an HC CDR1 comprising an amino acid sequence 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% identical to SEQ ID NO: 49, (b) an HC CDR2 comprising an amino acid sequence 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% identical to SEQ ID NO: 50, and (c) an HC CDR3 comprising an amino acid sequence 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% identical to SEQ ID NO: NO:51 has an amino acid sequence that is 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% identical; and a light chain variable domain (V L ): (d) an LC CDR1 comprising an amino acid sequence 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% identical to SEQ ID NO: 52, (e) an LC CDR2 comprising an amino acid sequence 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% identical to SEQ ID NO: 53, and (f) an LC CDR3 comprising an amino acid sequence 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% identical to SEQ ID NO: NO:54 has an amino acid sequence that is 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% identical; (iii) comprises a heavy chain variable domain (V H): (a) HC CDR1 comprising an amino acid sequence 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% identical to SEQ ID NO: 63, (b) HC CDR2 comprising an amino acid sequence 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% identical to SEQ ID NO: 64, and (c) HC CDR3 comprising an amino acid sequence 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% identical to SEQ ID NO: NO:65 has an amino acid sequence that is 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% identical; and a light chain variable domain (V L ): (d) an LC CDR1 comprising an amino acid sequence 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% identical to SEQ ID NO: 66, (e) an LC CDR2 comprising an amino acid sequence 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% identical to SEQ ID NO: 67, and (f) an LC CDR3 comprising an amino acid sequence 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% identical to SEQ ID NO: NO:68 has an amino acid sequence that is 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% identical; or (iv) comprises a heavy chain variable domain (V H) 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) a 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, and (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 a light chain variable domain (VL) comprising: (d) a 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) a 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, and (f) a LC 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: 82. L ) 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) a 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, and (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 a light chain variable domain (VL) comprising: (d) a 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) a 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, and (f) a LC 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: 82.

[0037] In some embodiments, the anti-CD22 antibody comprises a VHcomprising at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c). H ; a VLcomprising at least two CDRs selected from (i)(d)-(f), (ii)(d)-(f), (iii)(d)-(f), or (iv)(d)-(f). L ; or the VHcomprises at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c). Hcomprises at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c), and the V L comprises at least two CDRs selected from (i)(d)-(f), (ii)(d)-(f), (iii)(d)-(f), or (iv)(d)-(f).

[0038] In some aspects, the disclosure provides an antibody comprising: (i) an HC CDR1, an HC CDR2, an HC CDR3, an LC CDR1, an LC CDR2, and / or an LC CDR3 of any one of the antibodies listed in Table 1; (ii) a VH and / or a VL of any one of the antibodies listed in Table 1; or (iii) a heavy chain and / or a 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 that is 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% identical to SEQ ID NO: 11, and a light chain comprising an amino acid sequence that is 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% identical to SEQ ID NO: 12; (ii) a heavy chain comprising an amino acid sequence that is 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% identical to SEQ ID NO: 57, and a light chain comprising an amino acid sequence that is 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% identical to SEQ ID NO: 58; (iii) a heavy chain comprising an amino acid sequence that is 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% identical to SEQ ID NO: 71, and a light chain comprising an amino acid sequence that is 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% identical to SEQ ID NO: 72; or (iv) a heavy chain comprising an amino acid sequence that is 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% identical to SEQ ID NO: 85, and a light chain comprising an amino acid sequence that is 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% identical 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 present disclosure provides an antibody comprising a HC CDR3 comprising the amino acid sequence of ARELTGDAFDX7 (SEQ ID NO: 35), wherein X7 is I or L.

[0041] In some embodiments, the antibody further comprises 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, and / or 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.

[0042] In some embodiments, the antibody further comprises: 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 a 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 present disclosure provides an antibody comprising: 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 a LC CDR3 comprising the amino acid sequence of HQSSX10 LC CDR3 of the amino acid sequence of EPYT (SEQ ID NO: 38), wherein X 10 is T, R, or S.

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

[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 described herein are IgGl, IgG2, and IgG3, IgG4, and IgM, and IgAl, and IgA2, and IgD, or IgE antibodies, or the antigen-binding fragments from the antibodies are fragments of IgGl, IgG2, and IgG3, IgG4, and IgM, and IgAl, and IgA2, and IgD, or IgE antibodies. In some embodiments, the isolated antibodies described herein are IgGl antibodies or IgG4 antibodies, or the antigen-binding fragments from the antibodies are fragments of IgGl antibodies 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, where the heterologous moiety is a polypeptide, the antibody or antigen-binding fragment thereof can be a fusion protein having 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 a drug), or a detectable label such as, but not limited to, a radiolabel, an enzymatic label, a detectable label such as a fluorescent label or a luminescent label, or an affinity label such as biotin or streptavidin. Suitable radiolabels include, for example 32 P, 33 P,14 C, 125 I, 131 I, 35 S and 3 H. Suitable fluorescent labels include, but are not limited to, fluorescein, fluorescein isothiocyanate (FITC), green fluorescent protein (GFP), DyLight TM 488, phycoerythrin (PE), propidium iodide (PI), PerCP, PE-Alexa 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 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 comprising 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 another aspect, the disclosure features an isolated nucleic acid encoding a polypeptide, wherein the polypeptide is or comprises any one or more of the antibodies or antigen-binding fragments thereof described herein, any fusion protein described herein, or any bispecific or multispecific polypeptide described herein.

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

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

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

[0058] In yet another aspect, the disclosure features a method for treating a B-cell disorder, the method 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) any one or more antibodies or antigen-binding fragments thereof described herein (including conjugates), (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 nucleic acids described herein; (v) any one or more expression vectors described herein; (vi) any one or more recombinant cells described herein; (vii) any one or more isolated polypeptides described herein; and / or (viii) any one or more pharmaceutical compositions described herein.

[0059] In some embodiments, the B-cell disorder is an autoimmune disease, such as wherein 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 a cancer. The cancer can be, e.g., a B-cell lymphoma, such as a non-Hodgkin lymphoma. The non-Hodgkin lymphoma can be, e.g., Burkitt lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma.

[0061] In yet another aspect, the present disclosure features a method for preventing, reducing, delaying, or inhibiting the proliferation and / or growth of a cancer cell, comprising contacting the cancer cell with a therapeutic agent that binds to CD22 expressed on the surface of the cancer cell, wherein the therapeutic agent is: (i) any one or more antibodies or antigen-binding fragments thereof described herein (including conjugates), (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 can be administered by intravenous, intraperitoneal, intracerebral (intraparenchymal), intracerebroventricular, intramuscular, subcutaneous, intraocular, intraarterial, intraportal, or intralesional routes of injection; by sustained release systems, or by implantation devices. In certain embodiments, the compositions can be administered by bolus injection or continuously by infusion or by implantation devices.

[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 expressing 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 disclosure provides a method for treating a B-cell disorder described herein. In some embodiments, the immune cell is administered intravenously. In some embodiments, the immune cell is administered subcutaneously. BRIEF DESCRIPTION OF DRAWINGS

[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 the compositions and methods disclosed herein.

[0072] Figures 1A-1D Sensorgrams showing detector response versus time for the interaction between CD22 mAb-1 Figure 1A ), mAb-2 Figure 1B ), mAb-3 Figure 1C ), and mAb-4 Figure 1D ) and immobilized recombinant human CD22. DETAILED DESCRIPTION

[0073] The present disclosure is based, at least in part, on the development of anti-CD22 antibodies and variants thereof that exhibit 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] The foregoing and other aspects, implementations, acts, functions, features, and embodiments of the present teachings can be more fully understood with reference to the following description when considered in connection with the following drawings. I. DEFINITIONS

[0075] Administering: As used herein, the term "administering" or "administration" means providing an antibody or composition thereof to a subject in a physiologically and / or pharmacologically effective manner (e.g., to treat a condition in the subject).

[0076] Affinity Matured Antibodies: "Affinity matured antibodies" are used herein to refer to antibodies having one or more alterations in one or more CDRs compared to a parent antibody which do not have the alteration(s), which alteration(s) result in improvements in the affinity (i.e., KD, kd or ka) of the antibody for the target antigen. Exemplary affinity matured antibodies will have nanomolar or even picomolar affinities for the target antigen. A variety of procedures for affinity maturation are known in the art, including screening of combinatorial antibody libraries using biopanning. 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 is 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 mutagenesis at positions of selective mutagenesis and selective mutation at contact or hypervariable positions with active enhancing amino acid residues are described in U.S. Patent No. 6,914,128 Bl.

[0077] Antibody: As used herein, the term“antibody” refers to a polypeptide comprising at least one immunoglobulin variable domain or at least one site (e.g., paratope) that specifically binds to an antigen. In some embodiments, the antibody comprises a paratope. In some embodiments, the paratope comprises one or more complementarity determining regions (CDRs). In some embodiments, the antibody is a full-length antibody. In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, however, the antibody is a Fab fragment, a F(ab')2 fragment, a Fv fragment, or a scFv fragment. In some embodiments, the antibody is a nanobody derived from a camelid antibody or a nanobody derived from a shark antibody. In some embodiments, the antibody is a diabody. In some embodiments, the antibody comprises a framework having a human germline sequence. In another embodiment, the antibody comprises a heavy chain constant domain selected from the group consisting of IgG, IgG1, IgG2, IgG2A, IgG2B, IgG2C, IgG3, IgG4, IgA1, IgA2, IgD, IgM, and IgE constant domains. In some embodiments, the 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, the antibody comprises a constant domain, e.g., an Fc region. An immunoglobulin constant region refers to a heavy chain or light chain constant domain. Human IgG heavy chain 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, delta, epsilon, gamma, or mu heavy chain. In some embodiments, the heavy chain of an antibody described herein can comprise a human alpha, delta, epsilon, gamma, or mu heavy chain. In a particular embodiment, the antibody described herein comprises a human gamma 1 CH1, CH2, and / or CH3 domain. In some embodiments, the V H The amino acid sequence of the variable domain comprises the amino acid sequence of a human gamma (gamma) heavy chain constant region, such as any amino acid sequence known in the art. Non-limiting examples of human constant region sequences have been described in the art, see, e.g., U.S. Patent No. 5,693,780 and Kabat E A et al., (1991) supra. In some embodiments, the V HThe domain comprises an amino acid sequence that is at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or at least 99% identical to any of the variable chain constant regions provided herein. In some embodiments, the antibody is modified, e.g., 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 is conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glycosylphosphatidylinositolization (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules is a monosaccharide, disaccharide, oligosaccharide, or polysaccharide. In some embodiments, the one or more sugar or carbohydrate molecules is a branched oligosaccharide or branched polysaccharide. In some embodiments, the one or more sugar or carbohydrate molecules comprises 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 disclosure linked to a linker polypeptide or an immunoglobulin constant domain. A linker polypeptide comprises two or more amino acid residues linked by a peptide bond and serves 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, R.J. et al. (1994) Structure 2:1121-1123). Furthermore, the antibody can be part of a larger immunoadhesion molecule, formed through covalent or noncovalent association of an antibody or antibody portion with one or more other proteins or peptides. Examples of such immunoadhesion molecules include use of the streptavidin core region to produce a tetrameric scFv molecule (Kipriyanov, S.M. et al. (1995) Human Antibodies and Hybridomas 6:93-101) and use of a cysteine residue

[0078] About: As used herein, the term “about” or “approximately,” applied to one or more values of a desired range, means values that are similar to a stated reference value. In certain embodiments, the term “about” or “approximately” means a range of values that fall within 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in either direction (greater than or less than) of the stated reference value, unless otherwise stated or otherwise clear from the context (except where such number would exceed 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 comprises a heavy chain variable region (VH) and a light chain variable region (VL) that generally participate in antigen binding. The VHand VLregions can be further subdivided into regions of hypervariability, also called “complementarity determining regions” (“CDRs”), interspersed with regions that are more conserved, termed “framework regions” (“FRs”). Each VHand VLis composed of three CDRs and four FRs, arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The extent of the framework region and CDRs can be precisely defined using methods known in the art, e.g., by the Kabat definition, the IMGT definition, the Chothia definition, the AbM definition, and / or the contact definition, all of which are well known in the art. See, e.g., Kabat, E. A. et al. (1991) Sequences of Proteins of Immunological Interest, 5th Ed. U.S. Department of Health and Human Services, NIH Publication No. 91-3242; international ImMunoGeneTics information 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. (1997) J. Molec. Biol. 273:927-948; and Almagro, J. Mol. Recognit. 17:132-143 (2004). See also hgmp.mrc.ac.uk and bioinf.org.uk / abs. As used herein, CDR can refer to CDRs defined by any method known in the art. Two antibodies having identical CDRs means that the two antibodies have identical amino acid sequences for that CDR as determined by the same method (e.g., IMGT definition).

[0080] In certain embodiments, there are three CDRs in each variable region of the heavy and light chains, which are designated CDR1, CDR2, and CDR3 for each variable region. The term "CDR set" as used herein refers to a set of three CDRs present in a single variable region capable of binding an antigen. The exact boundaries of these CDRs have been defined differently according to different systems. The system 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 variable region of an antibody, but also provides precise residue boundaries defining the three CDRs. These CDRs can be referred to as Kabat CDRs. Sub-portions of CDRs can be designated LC CDR1, LC CDR2, and LC CDR3 or HC CDR1, HC CDR2, and HC CDR3, where "LC" and "HC" designate light chain regions and heavy chain regions, respectively. These regions can be referred to as Chothia CDRs, the boundaries of which overlap with the Kabat CDRs. Other boundaries defining CDRs overlapping with the Kabat CDRs have been described by Padlan (FASEB J. 9: 133-139 (1995)) and MacCallum (J Mol Biol 262(5): 732-45 (1996)). Still other CDR boundary definitions can not strictly follow one of the above systems, but will still overlap with the Kabat CDRs, albeit shortened or lengthened, according to particular residues or groups of residues or even entire CDRs that are not predicted or found experimentally to significantly impact antigen binding. Methods used herein can utilize CDRs defined according to any of these systems, although preferred embodiments use the Kabat or Chothia defined CDRs.

[0081] In certain embodiments, the CDRs of an antibody can have different amino acid sequences when different definition systems are used (e.g., IMGT definition, Kabat definition, or Chothia definition). The definition systems annotate each amino acid in a given antibody sequence (e.g., a VH or VL sequence) with a number, 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 is able to obtain the CDR sequences using the different numbering systems for the anti-CD22 antibodies provided in Table 1. Table 2. CDR Definitions IMGT 1 ]]> Kabat 2 ]]> Chothia 3 ]]> HC CDR1 27-38 31-35 26-32 HC CDR2 56-65 50-65 53-55 HC CDR3 105-116 / 117 95-102 96-101 LC CDR1 27-38 24-34 26-32 LC CDR2 56-65 50-56 50-52 LC CDR3 105-116 / 117 89-97 91-96 1 international ImMunoGeneTics information imgt.org, Lefranc, M.-P. et al., Nucleic Acids Res. 27:209-212 (1999) 2 Kabat et al., (1991) Sequences of Proteins of Immunological Interest, 5th Ed. U.S. Department of Health and Human Services, NIH Publication No. 91-3242 3 Chothia et al., J. Mol. Biol. 196:901-917 (1987)

[0082] CDR-grafted antibody: The term "CDR-grafted antibody" refers to an antibody that comprises heavy and light chain variable region sequences from one species but in which the sequence of one or more CDR regions of the VHand / or VLis replaced with CDR sequences of another species, such as an antibody having murine heavy and light chain variable regions in which one or more murine CDRs (e.g., CDR3) have been replaced with human CDR sequences.

[0083] Chimeric antibody: The term "chimeric antibody" refers to an antibody that comprises 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 human constant regions.

[0084] Complementary: As used herein, the term “complementary” refers to the ability of two nucleotides or sets of two nucleotides to pair precisely. In particular, complementary is a term that characterizes the degree of hydrogen-bond pairing that results in binding between two nucleotides or sets of two nucleotides. For example, if a base at one position of an oligonucleotide is capable of hydrogen-bonding with a base at a corresponding position of a target nucleic acid (e.g., mRNA), then the bases are considered to be complementary to one another at that position. Base pairing can include canonical Watson-Crick base pairing and non-Watson-Crick base pairing (e.g., wobble base pairing and Hoogsteen base pairing). For example, in some embodiments, for complementary base pairing, an adenosine-type base (A) is complementary to a thymidine-type base (T) or a uracil-type base (U), a cytosine-type base (C) is complementary to a guanosine-type base (G), and a universal base such as 3-nitropyrrole or 5-nitroindole can hybridize to and be considered complementary to any A, C, U, or T. Inosine (I) has also been considered in the art to be a universal base and to be considered complementary to any A, C, U, or T.

[0085] 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 binding of the first antibody to its epitope is detectably reduced in the presence of the second antibody as compared to the binding of the first antibody in the absence of the second antibody. The alternative can be, but is not necessarily, that the binding of the second antibody to its epitope is also detectably reduced in the presence of the first antibody. That is, the first antibody can inhibit the binding of the second antibody to its epitope, while the second antibody does not inhibit the binding of the first antibody to its respective epitope. However, where each antibody detectably inhibits the binding of the other antibody to its epitope or ligand, whether to the same, greater, or lesser extent, these antibodies are said to “cross-compete” for binding to 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 appreciate that such competing and / or cross-competing antibodies are encompassed and can be used in the methods and / or compositions provided herein.

[0086] Conjugate: As used herein, “conjugate” means that two entities are associated, preferably with sufficient affinity to achieve a therapeutic / diagnostic benefit of the association between the two entities. The association between the two entities can be direct or via a linker, such as a polymeric linker. Conjugation can include covalent or non-covalent bonding as well as other forms of association, such as one entity being trapped on or within another entity, or one or both entities being trapped on or within a third entity, such as a micelle.

[0087] 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 made according to methods known to those of ordinary skill in the art for altering polypeptide sequences, such as can be found in references that compile such methods, e.g., Molecular Cloning: A Laboratory Manual, J. Sambrook et al., eds., 4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 2012, or Current Protocols in Molecular Biology, F. M. Ausubel et al., eds., John Wiley & Sons, Inc., New York. Conservative substitutions of amino acids include substitutions made 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.

[0088] Cross-reactivity: As used herein and in the context of a targeting agent (e.g., an antibody), the term “cross-reactivity” refers to the property of an agent to specifically bind with similar affinity or avidity to more than one antigen of a similar type or class (e.g., antigens of multiple homologs, paralogs, or orthologs). For example, in some embodiments, an antibody that is cross-reactive against human and non-human primate antigens of a similar type or class (e.g., human CD22 and non-human primate CD22) is capable of binding to the human and non-human primate antigens with similar affinity or avidity. In some embodiments, an antibody is cross-reactive against a human antigen and a rodent antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a rodent antigen and a non-human primate antigen of a similar type or class. In some embodiments, an antibody is cross-reactive against a human antigen, a non-human primate antigen, and a rodent antigen of a similar type or class.

[0089] Cytotoxic agent: As used herein, the term "cytotoxic agent" refers to a substance that inhibits or prevents the function of cells and / or causes cell death or destruction. Such agents are well known in the art and include, for example, radioisotopes (e.g., At211, I131, I125, Y90, Re186, Re188, Sm153, Bi212, P32, Pb212, and radioisotopes of Lu); chemotherapeutic agents or drugs (e.g., methotrexate, adriamicin, vinca alkaloids (vincristine, vinblastine, etoposide), doxorubicin, melphalan, mitomycin C, chlorambucil, daunorubicin, or other intercalating agents); growth inhibitory agents; enzymes and fragments thereof, such as nucleolytic enzymes; antibiotics; toxins, such as small molecule toxins or enzymatically active toxins of bacterial, fungal, plant, or animal origin, including fragments and / or variants thereof; and various anti-tumor or anti-cancer agents described below.

[0090] Chemotherapeutic agent: As used herein, "chemotherapeutic agent" refers to a chemical compound that can be used to treat proliferative disorders such as cancer (e.g., cancer that expresses CD22). These agents can be, for example, alkylating agents such as thiotepa and cyclophosphamide. Alkyl sulfonates, such as busulfan, improsulfan, and piposulfane; aziridines, such as benzodopa, carbocuone, meturedopa, and uredopa; ethyleneimines and methylamylamines, including hexamethylmelamine, triethylenemethylamine, triethylenephosphamide, triethylene-thiophosphamide, and trishydroxymethylmelamine; acetogenins (especially bulatacin and bulatacinone); delta-9-tetrahydrocannabinol (dronabinol, MARINOL); β-lapacona; lapacol; colchicine; betulinic acid; camptothecins (including the synthetic analogue topotecan); CPT-11 (irinotecan, CAMPTOSAR), acetylcamptothecin, scopolectin, and 9-aminocamptothecin); bryostatin; callistatin; CC-1065 (including its synthetic analogs, adozelesin, carzelesin, and bizelesin); podophyllotoxin; podophyllinic acid; teniposide; a cryptophycin (particularly cryptophycin 1 and cryptophycin 8); dolastatin; a duocarmycin (including the synthetic analogs, KW-2189 and CB1-TM1); eleutherobin; pancratistatin; a sarcodictiin; -pongistatin; a nitrogen mustard such as chlorambucil, chlornaphazine, colfosfamide, estramustine, ifosfamide, mechlorethamine, mechlorethamine oxide hydrochloride, melphalan, novembichin, phenesterine, prednimustine, trofosfamide, uracil mustard; a nitrosurea such as carmustine, chlorozotocin, fotemustine, lomustine, nimustine, and ranimnustine; an antibiotic such as the enediin antibiotic (e.g., calicheamicin, especially calicheamicin gammal and calicheamicin omegal (see, e.g., Agnew, Chem Intl. Ed. Engl., 33: 183-186 (1994)); dynemycin, including dynemycin A; an esperamicin;and chromophores of new calicheamicin conjugates and related chromoprotein antibiotics), aclacinomycin, actinomycin, autramycin, (azaserin), diazomycin, bleomycin, cactinomycin, carabicin, carminomycin, carzinophilin, chromomycin, dactinomycin, daunorubicin, detorrubicin, 6-diazo-5-oxo-L-norleucine, doxorubicin (including morpholino-doxorubicin, cyanomorpholino-doxorubicin, 2-pyrrolino-doxorubicin and deoxydoxorubicin), epirubicin, esorubicin, idarubicin, marcellomycin, mitomycin (such as mitomycin C), mycophenolic acid, nogalamycin, olivomycin, peplomycin, porfiromycin, puromycin, chelamicin, rodrububicin, streptonigrin, streptozocin, tubercidin, ubenimex, zinostatin, zorubicin; antimetabolites such as methotrexate and 5-fluorouracil (5-FU); folate analogues such as denopterin, methotrexate, pteropterin, trimetrexate; purine analogues such as fludarabine, 6-mercaptopurine, tiamiprine, thioguanine; pyrimidine analogues such as ancitabine, azacitidine, 6-azauridine, carmofur, cytarabine, dideoxyuridine, doxifluridine, enocythabin, floxuridine;androgens, such as calusterone, dromostanolone propionate, epitiostanol, mepitiostane, testolactone; anti-adrenal agents, such as aminoglutethimide, mitotane, trilostane; folate replenisers, such as folic acid; aceglatone; aldophosphamide glycoside; aminolevulinic acid; eniluracil; amsacrine; bestrabuchil; bisantrene; edatraxate; defofamine; demecolcine; diaziquone; elfornitin; elliptinium acetate; epothilone; etoglucid; gallium nitrate; hydroxyurea; lentinan; lonidainin; maytansinoid, such as maytansine and ansamitocin; mitoguazone; mitoxantrone; mopidanmol; nitraerine; pentostatin; phenamet; pirarubicin; losoxantrone; 2-ethylhydrazide; procarbazine; Polysaccharide-K Complex (JHS Natural Products, Eugene, OR); razoxane; rhizoxin; sizofiran; spirogermanium; tenuazonic acid; triazicuone; 2,2',2"-trichlorotriethylamine, trichothecenes (particularly T-2 toxin, verracurin A, roridin A, and anguidine), urethane, vindesine (ELDISINE, FILDESIN), dacarbazine, mannomustine, mitobronitol, mitolactol, pipobroman, gacytosin, cytarabine ("Ara-C"), thiotepa, taxoids such as paclitaxel (TAXOL, Bristol-Myers Squibb Oncology, Princeton, NJ), ABRAXANE TM , a nanoparticulate formulation with paclitaxel albumin (American Pharmaceutical Partners, Schaumberg, Illinois) and doxetaxel (Taxotere®) (Rhone-Poulenc Rorer, Antony, France); chloranbuchil; gemcitabine (GEMZAR); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine (Rhone-Poulenc Rorer, Antony, France); chloranbuchil; gemcitabine (GEMZAR); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine (Rhone-Poulenc Rorer, Antony, France); chloranbuchil; gemcitabine (GEMZAR); 6-thioguanine; mercaptopurine; methotrexate; platinum analogs such as cisplatin and carboplatin; vinblastine Novantrone; edatrexate; Daunomycin; aminopterin; ibandronate; topoisomerase inhibitor RFS 2000; difluoromethylornithine (DMFO); retinoids, such as retinoic acid; capecitabine pharmaceutically acceptable salt, acid, or derivative of any of the foregoing; and combinations of two or more of the foregoing, such as CHOP, an abbreviation for a combination therapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone; CVP, an abbreviation for a combination therapy of cyclophosphamide, vincristine, and prednisolone; and FOLFOX, an abbreviation for an oxaliplatin treatment regimen (ELOXATIN®) in combination with 5-FU and leucovorin. TM ) with 5-FU and leucovorin.

[0091] Effective amount: As used herein, “effective amount” means the amount of each active agent (e.g., an anti-CD22 antibody) alone or in combination with one or more other active agents required to confer the desired effect (e.g., a therapeutic effect on a subject). In some embodiments, the therapeutic effect is a reduction in CD22 levels or activity, and / or a lessened disease condition (e.g., a B-cell disorder).

[0092] Framework: As used herein, the term “framework” or “framework sequence” refers to the remaining sequence of a variable region minus the CDRs. Because the exact definition of CDR sequences can be determined by different systems, the meaning of framework sequence is subject to correspondingly different interpretations. The 6 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 on the light and heavy chains into 4 subregions (FR1, FR2, FR3, and FR4) on each chain, with CDR1 between FR1 and FR2, CDR2 between FR2 and FR3, and CDR3 between FR3 and FR4. In the absence of a particular subregion designated as FR1, FR2, FR3, or FR4, framework region, as otherwise referred to, denotes the combined FRs within the variable region of a single naturally occurring immunoglobulin chain. As used herein, FR denotes one of the four subregions, and FR denotes 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, art-known acceptor sequences can be used in the antibodies disclosed herein.

[0093] Human antibody: As used herein, the term "human antibody" is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. The human antibodies of the disclosure can include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutation in vivo), for example in the CDRs and in particular in the CDR3. However, the term "human antibody", as used herein, is not intended to include antibodies having binding sites derived from the germline of another mammalian species, such as a mouse.

[0094] Humanized antibody: The term "humanized antibody" refers to an antibody that comprises heavy and light chain variable region sequences from a non-human species (e.g., a mouse) but in which at least a portion of the variable region sequences has been altered, i.e., changed 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, and then humanizing the antibody using in vitro genetic engineering, such as those disclosed in Kasaian et al., PCT Publication No. WO 2005 / 123126 A2. H and / or V L sequences have been changed 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, and then humanizing the antibody using in vitro genetic engineering, such as those disclosed in Kasaian et al., PCT Publication No. WO 2005 / 123126 A2.

[0095] Humanized antibodies are human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some embodiments, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies can comprise residues that are not found in the recipient antibody or in the CDR or framework sequences of the donor antibody, but are introduced to further improve and optimize antibody performance. Typically, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will include at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. The antibody can have a Fc region modified as described in WO 99 / 58572. Other forms of humanized antibodies have one or more CDRs (one, two, three, four, five, six) altered relative to the original antibody, also referred to as "derived from" one or more CDRs from the original antibody. Humanized antibodies can also involve affinity maturation.

[0096] In some embodiments, humanization is achieved by grafting CDRs (e.g., as shown in Table 1) into human variable domains (e.g., IGKV1-NL1*01 and IGHV1-3*01 human variable domains). In some embodiments, an anti-CD22 antibody of the present disclosure is a humanized variant comprising one or more amino acid substitutions (e.g., in the VH framework regions) compared to any one of the VHs listed in Table 1, and / or one or more amino acid substitutions (e.g., in the VL framework regions) compared to any one of the VLs listed in Table 1.

[0097] Isolated antibody: As used herein, “isolated antibody” is intended to refer to an antibody that is substantially free of other antibodies having different antigenic specificities (e.g., an isolated antibody that specifically binds CD22 that is substantially free of antibodies that specifically bind antigens other than CD22). An isolated antibody that specifically binds CD22 may, however, have cross-reactivity to other antigens. Moreover, an isolated antibody can be substantially free of other cellular material and / or chemicals.

[0098] Kabat numbering: The terms “Kabat numbering,” “Kabat definition,” and “Kabat labeling” are used interchangeably herein. These terms, which are well-recognized in the art, refer to a numbering system for amino acid residues in the heavy and light chain variable regions of an antibody or antigen-binding portion thereof that are more variable (i.e., hypervariable) than other amino acid residues (Kabat et al. (1971) Ann. N Y Acad. Sci. 190:382-391 and Kabat, E. A. et al. (1991) Sequences of Proteins of Immunological Interest, 5th Ed. U.S. Department of Health and Human Services, NIH Publication No. 91-3242). For the heavy chain variable region, the hypervariable regions range from amino acid positions 31 to 35 of CDR1, amino acid positions 50 to 65 of CDR2, and amino acid positions 95 to 102 of CDR3. For the light chain variable region, the hypervariable regions range from amino acid positions 24 to 34 of CDR1, amino acid positions 50 to 56 of CDR2, and amino acid positions 89 to 97 of CDR3.

[0099] Recombinant antibody: As used herein, the term "recombinant antibody" is intended to include all antibodies that are prepared, expressed, created or isolated by recombinant means, such as antibodies expressed using a recombinant expression vector transfected into a host cell (described in greater detail herein), including, for example, antibodies isolated from a recombinant, combinatorial human antibody library (Hoogenboom H.R., (1997) TIB Tech. 15:62-70; Azzazy H. and Highsmith W.E., (2002) Clin. Biochem. 35:425-445; Gavilondo J.V. and Larrick J.W. (2002) BioTechniques 29:128-145; Hoogenboom H. and Chames P. (2000) Immunology Today 21 :371-378), antibodies isolated from an animal (e.g., a mouse) that is transgenic for human immunoglobulin genes (see e.g., Taylor, L.D. et al. (1992) Nucl. Acids Res. 20:6287-6295; Kellermann S-A. and Green L.L. (2002) Current Opinion in Biotechnology 13:593-597; Little M. et al. (2000) Immunology Today 21 :364-370) or antibodies produced, expressed, created or isolated by any other means involving splicing of human immunoglobulin gene sequences to other DNA sequences. In some embodiments, provided herein are recombinant human antibodies. In certain embodiments, such recombinant human antibodies have variable and constant regions derived from human germline immunoglobulin sequences. In certain embodiments, however, such recombinant human antibodies are subjected to in vitro mutagenesis (or, when an animal transgenic for human Ig sequences is used, in vivo somatic mutagenesis), and thus the amino acid sequences of the V H region and V L region of the recombinant antibodies are sequences that, while derived from and related to human germline V H and V L sequences, can not naturally exist within the human antibody germline repertoire in vivo. One embodiment of the present disclosure provides fully human antibodies capable of binding to human CD22, which can be generated using techniques well known in the art, such as, but not limited to, using human Ig phage libraries, such as those disclosed in Jermutus et al., PCT Publication No. WO 2005 / 007699 A2.

[0100] Selective: As used herein, the term "selective" or "selectively" refers to the ability of a molecule to produce an effect (e.g., inhibit, antagonize, agonize, etc.) relative to its target molecule as compared to a reference molecule. For example, a molecule that selectively inhibits its target molecule means that the molecule is capable of inhibiting its target molecule to an extent that is distinguishable from a reference molecule in an inhibition assay or other inhibition context. For example, with respect to an inhibitor, the term "selectively inhibits" refers to the ability of an inhibitor to inhibit its target molecule to an extent that is distinguishable from a reference molecule that is not substantially inhibited in an inhibition assay, e.g., to an extent that permits selective inhibition of the target molecule, as described herein. Once the reaction is terminated, the signal produced by the inhibition of the target molecule can be measured. The half maximal inhibitor concentration of the target molecule and the reference molecule can be calculated. In some embodiments, a molecule described herein selectively binds to a target molecule. In some embodiments, a molecule described herein selectively inhibits a target molecule (e.g., CD22). In some embodiments, a molecule described herein selectively antagonizes a target molecule (e.g., CD22). In some embodiments, a molecule described herein selectively neutralizes a target molecule (e.g., CD22).

[0101] Specific binding: As used herein, the term "specific binding" refers to the ability of a molecule to bind to a binding partner with a degree of affinity or avidity that enables the molecule to be used in a binding assay or other binding context to distinguish the binding partner from an appropriate control. With respect to an antibody, the term "specific binding" refers to the ability of an antibody to bind to a particular antigen with a degree of affinity or avidity that enables the antibody to be used to distinguish the particular antigen from other antigens, as described herein. In some embodiments, an antibody specifically binds to a target if the KD of the antibody binding to the target is at least about 10 -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 M, or lower. In some embodiments, an antibody specifically binds to CD22.

[0102] 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 / or one or more conditions resulting from a B-cell disorder.

[0103] Treatment: As used herein, the term “treating” or “treatment” refers to the application or administration of a composition including one or more active agents (e.g., an anti-CD22 antibody) to a subject with the intent to cure, heal, alleviate, relieve, alter, remedy, improve, or affect a disorder, symptom of a disorder, or predisposition toward a disorder. Alleviating a disorder of interest includes delaying or preventing development or progression of a disease, or reducing disease severity. II. Antibodies and Related Compositions (a) Anti-CD22 Antibodies

[0104] In some embodiments, an 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, an anti-CD22 antibody described herein specifically binds to any extracellular epitope of CD22 or an epitope exposed to an antibody. In some embodiments, provided herein are anti-CD22 antibodies that specifically bind to CD22 from a human, a non-human primate, a mouse, a rat, and the like. In some embodiments, provided herein are anti-CD22 antibodies that bind to human CD22. In some embodiments, an anti-CD22 antibody described herein binds to an amino acid segment of human or non-human primate CD22. CD22 is a molecule belonging 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 immunoregulatory molecule (e.g., to prevent over-activation of the immune system and development of autoimmune diseases). In some embodiments, CD22 modulates 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).

[0105] In some embodiments, the anti-CD22 antibodies described herein specifically bind to human CD22. Exemplary amino acid sequences of human CD22 are set forth 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, 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.

[0106] 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 human CD22 extracellular domain are set forth in any one of SEQ ID NOs: 45-48.

[0107] Human CD22 full ECD domain 1-7 (SEQ ID NO: 45)

[0108] DSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILF HNPEYNKNTSKFDGTRLYESTKDGKVP SEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKHTPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQYAPEPSTVQILHSPAVEGSQVEFLCMSLANPLPTNYTWYHNGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILGTGQRGPGAELDVQYPPKKVTTVIQNPMPIREGDTVTLSCNYNSSNPSVTRYEWKPHGAWEEPSLGVLKIQNVGWDNTTIACAACNSWCSWASPVALNVQYAPRDVRVRKIKPLSEIHSGNSVSLQCDFSSSHPKEVQFFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEVLYAPRRLRVSMSPGDQVMEGKSATLTCESDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQGTNSVGKGRSPLSTLTVYYSPETIGRR

[0109] Human CD22 full ECD domain 1-7 with Avi-His tag (SEQ ID NO: 46)

[0110] DSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILF HNPEYNKNTSKFDGTRLYESTKDGKVP SEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKHTPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQYAPEPSTVQILHSPAVEGSQVEFLCMSLANPLPTNYTWYHNGKEMQGRTEEKVHIPKILPWHAGTYSCVAENILGTGQRGPGAELDVQYPPKKVTTVIQNPMPIREGDTVTLSCNYNSSNPSVTRYEWKPHGAWEEPSLGVLKIQNVGWDNTTIACAACNSWCSWASPVALNVQYAPRDVRVRKIKPLSEIHSGNSVSLQCDFSSSHPKEVQFFWEKNGRLLGKESQLNFDSISPEDAGSYSCWVNNSIGQTASKAWTLEVLYAPRRLRVSMSPGDQVMEGKSATLTCESDANPPVSHYTWFDWNNQSLPYHSQKLRLEPVKVQHSGAYWCQGTNSVGKGRSPLSTLTVYYSPETIGRRGGGGSGLNDIFEAQKIEWHEGGGGSHHHHHH

[0111] Human CD22 full ECD domains 4-7 with Avi-His tag (SEQ ID NO: 47)

[0112] QYAPEPSTVQ ILHSPAVEGSQ VEFLCMSLAN PLPTNYTWYH NGKEMQGRTE EKVIPKILPWH AGTYSCVAEN ILGTGQRGPG AELDVQYPPK KVTTVIQNPM PIREGDTVTL SCNYNSSNPS VTRYEWKPH GAWEEPSLGV LKIQNVGWDN TTIACAACNS WCSWASPVAL NVQYAPRDV RVRKIKPLSE IHSGNSVSLQ CDFSSSHPK EVQFFWEKNG RLLGKESQLN FDSISPEDAG SYSCWVNNS IGQTASKAWT LEVLYAPRR LRVSMSPGDQ VMEGKSATL TCESDANPPV SHYTWFDWN NQSLPYHSQ KLRLEPVKVQ HSGAYWCQGT NSVGKGRSP LSTLTVYYSP ETIGRRGGG GSGLNDIFEA QKIEWHEGG GGSHHHHHH

[0113] Human CD22 full ECD domains 1-3 with Avi-His tag (SEQ ID NO: 48)

[0114] DSSKWVFEHPETLYAWEGACVWIPCTYRALDGDLESFILFHNPEYNKNTSKFDGTRLYESTKDGKVPSEQKRVQFLGDKNKNCTLSIHPVHLNDSGQLGLRMESKTEKWMERIHLNVSERPFPPHIQLPPEIQESQEVTLTCLLNFSCYGYPIQLQWLLEGVPMRQAAVTSTSLTIKSVFTRSELKFSPQWSHHGKIVTCQLQDADGKFLSNDTVQLNVKHTPKLEIKVTPSDAIVREGDSVTMTCEVSSSNPEYTTVSWLKDGTSLKKQNTFTLNLREVTKDQSGKYCCQVSNDVGPGRSEEVFLQVQYAGGGGSGLNDIFEAQKIEWHEGGGGSHHHHHH

[0115] In some embodiments, an anti-CD22 antibody 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, about 10 to about 400 amino acids, about 50 to about 350 amino acids, about 100 to about 300 amino acids, about 150 to about 250 amino acids, about 200 to about 300 amino acids, or about 75 to about 150 amino acids in length. The fragment can comprise a contiguous number of amino acids from human CD22 (e.g., a human CD22 ECD domain as set forth in any one of SEQ ID NOs: 45-48, as described herein).

[0116] In some embodiments, an anti-CD22 antibody described herein specifically binds 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 Uniprot Accession Nos. P35329, Q3U0M3, Q9JHK8, A0A8B7H4W8, A0A087WQ27, A0A087WQV3, A0A087WR31, A0A087WR96, A0A087WST4, A0A1L1SSS3, A0A6I9LN61, A0A6I9LTY4, A0A6P5PYI2, or A0A6P5Q630.

[0117] In some embodiments, an anti-CD22 antibody described herein specifically binds to an epitope on mouse CD22 (e.g., an extracellular domain (ECD) of mouse CD22 described herein). An exemplary amino acid sequence of mouse CD22 extracellular domain is set forth in SEQ ID NO: 37.

[0118] Mouse CD22 full ECD domain (SEQ ID NO: 37)

[0119] SANDWTVDHPQTLFAWEGACIRIPCKYKTPLPKARLDNILL FQNYEFDKATKKFTGTVLYNATKTEKDPESELYLSKQGRVTFLGNRIDNCTLKIHPIRANDSGNLGLRMTAGTERWMEPIHLNVSEKPFQPYIQMPSEIRESQSVTLTCGLNFSCFGYDILLKWFLEDSEITSITSSVTSITSSVTSSIKNVYTESKLTFQPKWTDHGKSVKCQVQHSSKVLSERTVRLDVKYTPKLEIKVNPTEVEKNNSVTMTCRVNSSNPKLRTVAVSWFKDGRPLEDQELEQEQQMSKLILHSVTKDMRGKYRCQASNDIGPGESEEVELTVHYAPEPSRVHIYPSPAEEGQSVELICESLASPSATNYTWYHNRKPIPGDTQEKLRIPKVSPWHAGNYSCLAENRLGHGKIDQEAKLDVHYAPKAVTTVIQSFTPILEGDSVTLVCRYNSSNPDVTSYRWNPQGSGSVLKPGVLRIQKVTWDSMPVSCAACNHKCSWALPVILNVHYAPRDVKVLKVSPASEIRAGQRVLLQCDFAESNPAEVRFFWKKNGSLVQEGRYLSFGSVSPEDSGNYNCMVNNSIGETLSQAWNLQVLYAPRRLRVSISPGDHVMEGKKATLSCESDANPPISQYTWFDSSGQDLHSSGQK

[0120] 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, about 10 to about 400 amino acids, about 50 to about 350 amino acids, about 100 to about 300 amino acids, about 150 to about 250 amino acids, about 200 to about 300 amino acids, or about 75 to about 150 amino acids in length. The fragment can comprise a contiguous number of amino acids from mouse CD22 (e.g., a mouse CD22 ECD domain as set forth in SEQ ID NO: 37).

[0121] In some embodiments, an anti-CD22 antibody described herein specifically binds to non-human primate CD22. In some embodiments, the non-human primate is a rhesus macaque. Exemplary amino acid sequences of rhesus macaque 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.

[0122] In some embodiments, an anti-CD22 antibody described herein specifically binds to an epitope on rhesus macaque CD22 (e.g., an extracellular domain (ECD) of a rhesus macaque CD22 described herein). In some embodiments, an anti-CD22 antibody described herein can bind to a fragment of rhesus macaque CD22 (e.g., a rhesus macaque CD22 described herein) that can be about 5 to about 425 amino acids, about 10 to about 400 amino acids, about 50 to about 350 amino acids, about 100 to about 300 amino acids, about 150 to about 250 amino acids, about 200 to about 300 amino acids, or about 75 to about 150 amino acids in length. The fragment can comprise a contiguous number of amino acids from rhesus macaque CD22 (e.g., a rhesus macaque CD22 described herein).

[0123] In some embodiments, an anti-CD22 antibody described herein is a clone that is affinity matured. In some embodiments, an anti-CD22 antibody is at least about 10-fold more potent than the parent clone from which it was derived. -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 -13M or lower (e.g., as indicated by KD) binds specifically to CD22 (e.g., human, mouse, or non-human primate CD22). For example, an anti-CD22 antibody of the present disclosure can bind to a CD22 protein (e.g., human, mouse, or non-human primate CD22) with an affinity of between 5 pM and 500 nM, e.g., between 50 pM and 100 nM, between 500 pM and 50 nM, between 1 nM and 50 nM, between 2 nM and 20 nM, between 1 nM and 10 nM, between 1 nM and 3 nM, or between 2 nM and 5 nM. The present 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 lower (e.g., 80 nM or lower, 50 nM or lower, 20 nM or lower, 10 nM or lower, 5 nM or lower, 500 pM or lower, 50 pM or lower, or 5 pM or lower). Affinity and binding kinetics of an anti-CD22 antibody can be tested using any suitable method, including but not limited to biosensor technology (e.g., OCTET or BIACORE). In some embodiments, an anti-CD22 antibody described herein binds to CD22 (e.g., human or non-human primate CD22) with a KD in the nanomolar range.

[0124] Binding affinity (or binding specificity) can be determined by a variety of methods, including equilibrium dialysis, equilibrium binding, gel filtration, ELISA, surface plasmon resonance (SPR), fluorescence activated cell sorting (FACS), or spectroscopy (e.g., using fluorescence assays). Exemplary conditions for evaluating 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 KC1). These techniques can be used to measure the concentration of bound protein as a function of target protein concentration. The concentration of bound protein ([bound]) is typically related to the concentration of free target protein ([free]) by the following equation: [bound] = [free] / (Kd + [free])

[0125] However, it is not always necessary to determine KA precisely, as sometimes only a quantitative measure of affinity is needed, e.g., as determined using a method such as an ELISA or FACS analysis, which is proportional to KAand thus can be used for comparison, such as determining whether a higher affinity is, e.g., 2-fold, to obtain a qualitative measure of affinity, or to obtain an inference of affinity, e.g., by activity in a functional assay (e.g., an in vitro or in vivo assay).

[0126] Heavy chain (HC) and light chain (LC) sequences, heavy chain variable domain (VH) and light chain variable domain (VL), CDR sequences, and heavy and light chain constant region sequences of non-limiting examples of anti-CD22 antibodies are provided in Table 1. Table 1. Examples of anti-CD22 antibodies CDR sequences of CD22 mAbs defined by Kabat CDR consensus sequences defined by IMGT

[0127] In some embodiments, in accordance with the IMGT definition, the anti-CD22 antibodies of the present disclosure comprise the consensus sequences: HC CDR1 comprising the amino acid sequence of GFX1FX2X3YG (SEQ ID NO: 33), wherein X1is T or I, X2is S or R, and X3is S or N; HC CDR2 comprising the amino acid sequence of IYYDGX4X5X6(SEQ ID NO: 34), wherein X4is N or S, X5is K or N, and X6is K or N; HC CDR3 comprising the amino acid sequence of ARELTGDAFDX7, wherein X7is I or L; LC CDR1 comprising the amino acid sequence of QX8IGSX9, X8is S or R, and X9is S or H; LC CDR2 comprising the amino acid sequence of YAS; and / or LC CDR3 comprising the amino acid sequence of HQSSX 10 EPYT, wherein X 10 is T, R, or S. The consensus sequences of the anti-CD22 antibodies described herein can also be defined by the Kabat definition or the Chothia definition.

[0128] In some embodiments, an anti-CD22 antibody of the present disclosure comprises one or more HC CDR (e.g., HC CDR1, HC CDR2, or HC CDR3) amino acid sequences of any of the anti-CD22 antibodies selected from Table 1. In some embodiments, an anti-CD22 antibody of the present disclosure comprises the HC CDR1, HC CDR2, and HC CDR3 provided for any of the antibodies selected from Table 1. In some embodiments, an anti-CD22 antibody of the present disclosure comprises one or more LC CDR (e.g., LC CDR1, LC CDR2, or LC CDR3) amino acid sequences of any of the anti-CD22 antibodies selected from Table 1. In some embodiments, an anti-CD22 antibody of the present disclosure comprises the LC CDR1, LC CDR2, and LC CDR3 provided for any of the anti-CD22 antibodies selected from Table 1.

[0129] 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 as provided for any of the anti-CD22 antibodies selected from Table 1. In some embodiments, the antibody heavy and light chain CDR3 domains can play a particularly important role in the binding specificity / affinity of the antibody for the antigen. Accordingly, an anti-CD22 antibody of the present disclosure can comprise at least the heavy and / or light chain CDR3 of any of the anti-CD22 antibodies selected from Table 1.

[0130] In some embodiments, an isolated anti-CD22 antibody comprises a heavy chain variable region comprising a heavy chain CDR1 (HC CDR1), a heavy chain CDR2 (HC CDR2), and a heavy chain CDR3 (HC CDR3).

[0131] Functional variants of any of the exemplary anti-CD22 antibodies disclosed herein are also within the scope of the present disclosure. Functional variants can contain one or more amino acid residue variations in the V H and / or V L region, or in one or more HC CDRs and / or one or more LC CDRs, while retaining substantially similar binding and biological activity (e.g., substantially similar binding affinity, binding specificity, inhibitory activity, anti-inflammatory activity, or a combination thereof) to the reference antibody.

[0132] In some embodiments, any of the anti-CD22 antibodies of the present disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences that are substantially similar to any of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 sequences of one of the anti-CD22 antibodies selected from Table 1. In some embodiments, the position of one or more CDRs along the VH (e.g., HC CDR1, HC CDR2, or HC CDR3) and / or VL (e.g., LC CDR1, LC CDR2, or LC CDR3) regions of an antibody described herein can be altered by 1, 2, 3, 4, 5, or 6 amino acid positions, so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially 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). For example, in some embodiments, the position of a CDR defining any of the antibodies described herein can be altered by shifting the N-terminal and / or C-terminal boundary of the CDR by 1, 2, 3, 4, 5, or 6 amino acids relative to the CDR position of any of the antibodies described herein, so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially 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). 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 can be altered (e.g., shortened or lengthened) by 1, 2, 3, 4, 5, or more amino acids, so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially 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).

[0133] 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 anti-CD22 antibody selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% binding relative to the original antibody from which it is derived). 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 anti-CD22 antibody selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% binding relative to the original antibody from which it is derived). In some embodiments, the amino portion of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein is extended by one, two, three, four, five, or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any anti-CD22 antibody selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% binding relative to the original antibody from which it is derived). In some embodiments, the carboxyl portion of the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2 and / or LC CDR3 described herein is extended by one, two, three, four, five, or more amino acids compared to one or more of the CDRs described herein (e.g., CDRs from any anti-CD22 antibody selected from Table 1), so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% binding relative to the original antibody from which it is derived).In some embodiments, the amino portion of an HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein is shortened by one, two, three, four, five, or more amino acids compared to one or more of the CDRs described herein (e.g., from a CDR of any anti-CD22 antibody selected from Table 1) so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially 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). In some embodiments, the carboxy portion of an HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and / or LC CDR3 described herein is shortened by one, two, three, four, five, or more amino acids compared to one or more of the CDRs described herein (e.g., from a CDR of any anti-CD22 antibody selected from Table 1) so long as immunospecific binding to CD22 (e.g., human CD22) is maintained (e.g., substantially 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). Whether immunospecific binding to CD22 (e.g., human CD22) is maintained can be determined using any method, e.g., using binding assays and conditions described in the art.

[0134] In some examples, any of the anti-CD22 antibodies of the present disclosure have one or more CDR (e.g., HC CDR or LC CDR) sequences that are substantially similar to any of the CDR sequences of any of the anti-CD22 antibodies selected from Table 1. For example, these antibodies can include one or more CDR sequences from any of the anti-CD22 antibodies selected from Table 1 that contain up to 5, 4, 3, 2, or 1 amino acid residue variations in the corresponding CDR regions as compared to any of the CDRs provided 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., substantially maintained, e.g., at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95% relative to the binding of the original antibody from which it is derived). In some embodiments, any of the amino acid variations in any of the CDRs provided herein can be conservative variations. Conservative variations can be introduced into the CDRs at positions where the residues are less likely to be involved in interactions with the CD22 protein (e.g., human CD22 protein), e.g., as determined based on crystal structures. 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 comprises one or more 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 of the anti-CD22 antibodies selected from Table 1. In some embodiments, any of the VL domains provided herein comprises one or more 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 of the anti-CD22 antibodies selected from Table 1.

[0135] In some embodiments, the anti-CD22 antibodies of the present disclosure include any antibody comprising a heavy chain variable domain and / or a light chain variable domain selected from any of the anti-CD22 antibodies of Table 1, and variants thereof. In some embodiments, the anti-CD22 antibodies of the present disclosure include any antibody comprising a heavy chain variable pair and a light chain variable pair selected from any of the anti-CD22 antibodies of Table 1.

[0136] Aspects of the disclosure provide anti-CD22 antibodies having heavy chain variable (VH) and / or light chain variable (VL) domain amino acid sequences that are homologous to any of the heavy chain variable (VH) and / or light chain variable (VL) domain amino acid sequences described herein. In some embodiments, an anti-CD22 antibody comprises 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 of the anti-CD22 antibodies selected from Table 1. In some embodiments, the homologous heavy chain variable and / or light chain variable amino acid sequences are free of variation in any of the CDR sequences provided herein. For example, in some embodiments, some degree of sequence variation (e.g., 75%, 80%, 85%, 90%, 95%, 98%, or 99%) can occur in the heavy chain variable and / or light chain variable sequence (not including any of the CDR sequences provided herein). In some embodiments, any of the anti-CD22 antibodies provided herein comprise a heavy chain variable sequence and a light chain variable sequence comprising a framework sequence that is at least 75%, 80%, 85%, 90%, 95%, 98%, or 99% identical to the framework sequence of any of the anti-CD22 antibodies selected from Table 1.

[0137] 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 an HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 identical to the HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3 shown in Table 1, and comprises a humanized heavy chain variable region and / or a humanized light chain variable region.

[0138] In some embodiments, an anti-CD22 antibody of the disclosure is a humanized antibody comprising a VH containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH of any of the anti-CD22 antibodies listed in Table 1. Alternatively or additionally, an anti-CD22 antibody of the disclosure is a humanized antibody comprising a VL containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL of any of the anti-CD22 antibodies listed in Table 1. Anti-CD22 mAb-1 and variants

[0139] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 55. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 56.

[0140] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 having the amino acid sequence of SEQ ID NO: 50, a HC CDR3 having the amino acid sequence of SEQ ID NO: 51, a LC CDR1 having the amino acid sequence of SEQ ID NO: 52, a LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 54, according to the Kabat definition system.

[0141] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) as compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 51. “Collectively”, as used anywhere in the present disclosure, means that the total number of amino acid variations in all three heavy chain CDRs is within the defined range. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) as compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 52, a LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0142] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 52, a LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0143] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a HC CDR3 having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 52, a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0144] In some embodiments, an anti-CD22 antibody of the disclosure comprises a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the HC CDR3 having the amino acid sequence of SEQ ID NO: 51. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the LC CDR1 having the amino acid sequence of SEQ ID NO: 52, a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the LC CDR3 having the amino acid sequence of SEQ ID NO: 54.

[0145] 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.

[0146] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 55. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 56.

[0147] In some embodiments, an anti-CD22 antibody of the disclosure 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 as 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 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL as set forth in SEQ ID NO: 56.

[0148] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence of SEQ ID NO: 55; alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence of SEQ ID NO: 56. In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence of SEQ ID NO: 55 and a VL comprising an amino acid sequence of SEQ ID NO: 56. Anti-CD22 mAb-2 and variants

[0149] In some embodiments, an anti-CD22 antibody of the disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 of a heavy chain variable domain having an amino acid sequence of SEQ ID NO: 69. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 of a light chain variable domain having an amino acid sequence of SEQ ID NO: 70.

[0150] In some embodiments, an anti-CD22 antibody of the disclosure comprises, according to the Kabat definition system, a HC CDR1 having an amino acid sequence of SEQ ID NO: 63, a HC CDR2 having an amino acid sequence of SEQ ID NO: 64, a HC CDR3 having an amino acid sequence of SEQ ID NO: 65, a LC CDR1 having an amino acid sequence of SEQ ID NO: 66, a LC CDR2 having an amino acid sequence of SEQ ID NO: 67, and a LC CDR3 having an amino acid sequence of SEQ ID NO: 68.

[0151] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO:63, a HC CDR2 having the amino acid sequence of SEQ ID NO:64, and a HC CDR3 having the amino acid sequence of SEQ ID NO:65. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO:66, a LC CDR2 having the amino acid sequence of SEQ ID NO:67, and a LC CDR3 having the amino acid sequence of SEQ ID NO:68.

[0152] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO:63, a HC CDR2 having the amino acid sequence of SEQ ID NO:64, and a HC CDR3 having the amino acid sequence of SEQ ID NO:65. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO:66, a LC CDR2 having the amino acid sequence of SEQ ID NO:67, and a LC CDR3 having the amino acid sequence of SEQ ID NO:68.

[0153] 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 CDR2 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, an anti-CD22 antibody of the present disclosure comprises: 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.

[0154] 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 CDR2 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, an anti-CD22 antibody of the present disclosure comprises: 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.

[0155] 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.

[0156] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 69. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 70.

[0157] In some embodiments, an anti-CD22 antibody of the disclosure 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: 69. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises 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: 70.

[0158] 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. In some embodiments, an anti-CD22 antibody of the 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. Anti-CD22 mAb-3 and variants

[0159] In some embodiments, an anti-CD22 antibody of the disclosure comprises an HC CDR1, an HC CDR2, and an HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 83. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises an LC CDR1, an LC CDR2, and an LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 84.

[0160] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a HC CDR1 having the amino acid sequence of SEQ ID NO: 63, a HC CDR2 having the amino acid sequence of SEQ ID NO: 78, a HC CDR3 having the amino acid sequence of SEQ ID NO: 79, a LC CDR1 having the amino acid sequence of SEQ ID NO: 80, a LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 82, according to the Kabat definition system.

[0161] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a HC CDR1, a HC CDR2, and a HC CDR3 that collectively comprise no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) as compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 63, a HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a LC CDR1, a LC CDR2, and a LC CDR3 that collectively comprise no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) as compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 80, a LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0162] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 63, a HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 80, a LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0163] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 63, a HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or a HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 80, a LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or a LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to a LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0164] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 63, a HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 80, a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0165] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a VH comprising the amino acid sequence of SEQ ID NO: 83. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a VL comprising the amino acid sequence of SEQ ID NO: 84.

[0166] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 83. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 84.

[0167] In some embodiments, an anti-CD22 antibody of the disclosure 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. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises 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.

[0168] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence of SEQ ID NO: 83; alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising an amino acid sequence of SEQ ID NO: 84. In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising an amino acid sequence of SEQ ID NO: 83 and a VL comprising an amino acid sequence of SEQ ID NO: 84. Anti-CD22 mAb-4 and variants

[0169] In some embodiments, an anti-CD22 antibody of the disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 of a heavy chain variable domain having an amino acid sequence of SEQ ID NO: 7. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 of a light chain variable domain having an amino acid sequence of SEQ ID NO: 8.

[0170] In some embodiments, an anti-CD22 antibody of the disclosure comprises, according to the Kabat definition system, a HC CDR1 having an amino acid sequence of SEQ ID NO: 1, a HC CDR2 having an amino acid sequence of SEQ ID NO: 2, a HC CDR3 having an amino acid sequence of SEQ ID NO: 3, a LC CDR1 having an amino acid sequence of SEQ ID NO: 4, a LC CDR2 having an amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having an amino acid sequence of SEQ ID NO: 6.

[0171] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0172] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0173] In some embodiments, an anti-CD22 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0174] In some embodiments, an anti-CD22 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 2; and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 4; a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 6.

[0175] 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.

[0176] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 7. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 8.

[0177] In some embodiments, an anti-CD22 antibody of the disclosure 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: 7. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises 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: 8.

[0178] 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. 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. Additional Anti-CD22 Antibodies

[0179] In some embodiments, an anti-CD22 antibody of the disclosure comprises an HC CDR1, an HC CDR2, and an HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 21. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises an LC CDR1, an LC CDR2, and an LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 22.

[0180] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a HC CDR1 having the amino acid sequence of SEQ ID NO: 17, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, a HC CDR3 having the amino acid sequence of SEQ ID NO: 3, a LC CDR1 having the amino acid sequence of SEQ ID NO: 19, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 20, according to the Kabat definition system.

[0181] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a HC CDR1, a HC CDR2, and a HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 17, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a LC CDR1, a LC CDR2, and a LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 19, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0182] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 17, a HC CDR2 having the amino acid sequence of SEQ ID NO: 18, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, the anti-CD22 antibodies of the present disclosure comprise a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 19, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 20.

[0183] 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 CDR2 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, an anti-CD22 antibody of the present disclosure comprises: 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.

[0184] 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 CDR2 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, an anti-CD22 antibody of the present disclosure comprises: 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.

[0185] 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.

[0186] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 21. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 22.

[0187] In some embodiments, an anti-CD22 antibody of the disclosure 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: 21. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises 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: 22.

[0188] In some embodiments, an anti-CD22 antibody of the disclosure comprises an HC CDR1, an HC CDR2, and an HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 25. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises an LC CDR1, an LC CDR2, and an LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 26.

[0189] In some embodiments, an anti-CD22 antibody of the disclosure comprises, according to the Rabat definition system, 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.

[0190] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. “Collectively,” as used anywhere in the present disclosure, means that the total number of amino acid variations in all three heavy chain CDRs is within the defined range. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 19, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0191] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 23, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 19, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0192] In some embodiments, an anti-CD22 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 23; and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 19; a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0193] In some embodiments, an anti-CD22 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 23; and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 3. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 19; a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 24.

[0194] 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.

[0195] In some embodiments, an anti-CD22 antibody of the disclosure comprises a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 25. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 26.

[0196] In some embodiments, an anti-CD22 antibody of the disclosure 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: 25. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises 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: 26.

[0197] In some embodiments, an anti-CD22 antibody of the disclosure comprises an HC CDR1, an HC CDR2, and an HC CDR3 of a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 31. Alternatively or additionally, an anti-CD22 antibody of the disclosure comprises an LC CDR1, an LC CDR2, and an LC CDR3 of a light chain variable domain having the amino acid sequence of SEQ ID NO: 32.

[0198] In some embodiments, an anti-CD22 antibody of the disclosure comprises, according to the Rabat definition system, 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.

[0199] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 27, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) compared to a LC CDR1 having the amino acid sequence of SEQ ID NO: 29, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0200] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a HC CDR1, a HC CDR2, and a HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC CDR2 having the amino acid sequence of SEQ ID NO: 27, and a HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a LC CDR1, a LC CDR2, and a LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 29, a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and a LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0201] In some embodiments, an anti-CD22 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 27; and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 29; a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0202] In some embodiments, an anti-CD22 antibody of the present disclosure comprises: a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1; a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 27; and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 28. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises: a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 29; a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5; and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 30.

[0203] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a VH comprising the amino acid sequence of SEQ ID NO: 31. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a VL comprising the amino acid sequence of SEQ ID NO: 32.

[0204] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a VH comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 31. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a VL comprising no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 32.

[0205] In some embodiments, an anti-CD22 antibody of the present disclosure 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: 31. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises 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: 32.

[0206] In some embodiments, an anti-CD22 antibody of the present disclosure is a chimeric antibody, which can comprise heavy and light constant regions from human antibodies. A chimeric antibody refers to an antibody that has 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 those of an antibody derived from one mammal (e.g., a non-human mammal, such as a mouse, rabbit, and rat), while the constant portions are homologous to sequences in the antibody derived from another mammal, such as a human. In some embodiments, amino acid modifications can be made in the variable and / or constant regions.

[0207] In some embodiments, the anti-CD22 antibodies described herein are chimeric antibodies, which can comprise heavy and light constant regions from human antibodies. Chimeric antibodies refer to antibodies that have 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 mammal (e.g., a non-human mammal, such as a mouse, rabbit, and rat), while the constant portions are homologous to sequences in 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.

[0208] In some embodiments, the anti-CD22 antibodies of the present disclosure comprise a VL domain and / or a VH domain selected from any of the anti-CD22 antibodies of Table 1, and comprise an amino acid sequence comprising a constant region of an IgG, IgE, IgM, IgD, IgA, or IgY immunoglobulin molecule, any class (e.g., IgGl, IgG2, IgG3, IgG4, IgAl, and IgA2) or any subclass (e.g., IgG2a and IgG2b) of immunoglobulin molecules. Non-limiting examples of human constant regions are described in the art, e.g., see Kabat E A et al., (1991) supra. An example of a human IgGl constant region is given below: ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO: 9).

[0209] In some embodiments, the light chain of any of the anti-CD22 antibodies described herein can further comprise a light chain constant region (CL), which can 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 of CLs are provided below: RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC (SEQ ID NO: 10).

[0210] Other antibody heavy and light chain constant regions can be used in some embodiments, for example those provided in the IMGT database (www.imgt.org) or www.vbase2.org / vbstat.php., both of which are incorporated by reference herein.

[0211] In some embodiments, an anti-CD22 antibody described herein comprises a heavy chain comprising a VH as set forth 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, an anti-CD22 antibody described herein comprises a heavy chain comprising a VH as set forth in Table 1 or any variant thereof and a heavy chain constant region that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to SEQ ID NO: 9. In some embodiments, an anti-CD22 antibody described herein comprises a heavy chain comprising a VH as set forth in Table 1 or any variant thereof and a heavy chain constant region set forth in SEQ ID NO: 9.

[0212] In some embodiments, an anti-CD22 antibody described herein comprises a light chain comprising a VL as set forth 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, an anti-CD22 antibody described herein comprises a light chain comprising a VL as set forth in Table 1 or any variant thereof and a light chain constant region that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to SEQ ID NO: 10. In some embodiments, an anti-CD22 antibody described herein comprises a light chain comprising a VL as set forth in Table 1 or any variant thereof and a light chain constant region set forth in SEQ ID NO: 10.

[0213] Examples of IgG heavy and light chain amino acid sequences for the anti-CD22 antibodies described above are provided in Table 1.

[0214] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a heavy chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the heavy chain set forth in SEQ ID NO: 11. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a light chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the light chain set forth in SEQ ID NO: 12. In some embodiments, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 11. Alternatively or additionally, an anti-CD22 antibody described herein comprises a light chain comprising the amino acid sequence of SEQ ID NO: 12. In some embodiments, an anti-CD22 antibody described herein comprises 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.

[0215] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a heavy chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the heavy chain set forth in SEQ ID NO: 57. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a light chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the light chain set forth in SEQ ID NO: 58. In some embodiments, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 57. Alternatively or additionally, an anti-CD22 antibody described herein comprises a light chain comprising the amino acid sequence of SEQ ID NO: 58. In some embodiments, an anti-CD22 antibody described herein comprises 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.

[0216] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a heavy chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the heavy chain set forth in SEQ ID NO: 71. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a light chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the light chain set forth in SEQ ID NO: 72. In some embodiments, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 71. Alternatively or additionally, an anti-CD22 antibody described herein comprises a light chain comprising the amino acid sequence of SEQ ID NO: 72. In some embodiments, an anti-CD22 antibody described herein comprises 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.

[0217] In some embodiments, an anti-CD22 antibody of the present disclosure comprises a heavy chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the heavy chain set forth in SEQ ID NO: 85. Alternatively or additionally, an anti-CD22 antibody of the present disclosure comprises a light chain containing no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the light chain set forth in SEQ ID NO: 86. In some embodiments, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises 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, an anti-CD22 antibody described herein comprises a heavy chain comprising the amino acid sequence of SEQ ID NO: 85. Alternatively or additionally, an anti-CD22 antibody described herein comprises a light chain comprising the amino acid sequence of SEQ ID NO: 86. In some embodiments, an anti-CD22 antibody described herein comprises 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.

[0218] An anti-CD22 antibody 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 (such as Fab, F(ab'), F(ab')2, Fv), a single-chain antibody, a bispecific antibody, or a nanobody. In some embodiments, an anti-CD22 antibody described herein is a scFv. In some embodiments, an anti-CD22 antibody described herein is a scFv-Fab (e.g., a scFv fused to a portion of a constant region).

[0219] In some embodiments, a conservative mutation can be introduced into an antibody sequence (e.g., a CDR or framework sequence) at a position where a residue is less likely to be involved in interacting with a target antigen (e.g., CD22), e.g., as determined based on a crystal structure. In some embodiments, one, two, or more mutations (e.g., amino acid substitutions) are introduced into the Fc region of an anti-CD22 antibody described herein (e.g., in the CH2 domain (residues 231-340 of human IgGl) and / or the CH3 domain (residues 341-447 of human IgGl) and / or the hinge region, numbered according to the Kabat numbering system (e.g., the EU index in Kabat)) 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.

[0220] 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), as described, e.g., in U.S. Patent No. 5,677,425. The number of cysteine residues in the hinge region of the CH1 domain can be altered, e.g., to 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 of an antibody described herein (e.g., in the CH2 domain (residues 231-340 of human IgGl) and / or the CH3 domain (residues 341-447 of human IgGl) and / or the hinge region, numbered according to the Kabat numbering system (e.g., the EU index in Kabat)) 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 fragment thereof are known to those of skill in the art. Examples of mutations that can be made in an antibody Fc receptor to alter the affinity of the antibody for the Fc receptor are described in, e.g., Smith P et al., (2012) PNAS 109:6181-6186, U.S. Patent No. 6,737,056, and International Publication Nos. WO 02 / 060919, WO 98 / 23289, and WO 97 / 34631, which are incorporated herein by reference.

[0221] 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) to alter (e.g., shorten or increase) the in vivo half-life of the antibody. See, e.g., International Publication Nos. WO 02 / 060919, WO 98 / 23289, and WO 97 / 34631; and U.S. Patent Nos. 5,869,046, 6,121,022, 6,277,375, and 6,165,745, for examples of mutations that will alter (e.g., shorten or increase) the in vivo half-life of an antibody.

[0222] 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) to decrease the in vivo half-life of the anti-CD22 antibody. 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) to increase the in vivo half-life of the antibody. In some embodiments, the antibody can have one or more amino acid mutations (e.g., substitutions) in the second constant (CH2) domain (residues 231-340 of human IgGl) and / or the third constant (CH3) domain (residues 341-447 of human IgGl), numbered according to the EU index in Kabat (Kabat E A et al., (1991) supra). In some embodiments, the IgGl 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, numbered according to the EU index in Kabat. See U.S. Patent No. 7,658,921, which is incorporated herein by reference. This type of mutant IgG, termed a “YTE mutant,” has been demonstrated to show a four-fold increase in half-life compared to the wild-type version of the same antibody (see Dall’Acqua W F 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 of amino acid residues at positions 251-257, 285-290, 308-314, 385-389, and 428-436, numbered according to the EU index in Kabat.

[0223] In some embodiments, one, two, or more amino acid substitutions are introduced into the IgG constant domain Fc region of an anti-CD22 antibody to alter the effector function of the anti-CD22 antibody. The affinity-altered effector ligand can be, for example, an Fc receptor or the Cl component of complement. This approach is described in further detail in U.S. Patent Nos. 5,624,821 and 5,648,260 (e.g., L234A and L235A mutations). In some embodiments, deletion or inactivation of a constant region domain (by point mutation or other means) can reduce Fc receptor binding of the circulating antibody, thereby increasing tumor localization. See, e.g., U.S. Patent Nos. 5,585,097 and 8,591,886 for a description of mutations that result in deletion or inactivation of a constant domain and thereby increase tumor localization. In some embodiments, one or more amino acid substitutions can be introduced into the Fc region of an antibody described herein to remove potential glycosylation sites on the Fc region, which can reduce Fc receptor binding (see Shields R L et al., (2001) J Biol Chem 276: 6591-604).

[0224] In some embodiments, one or more amino acids in the constant region of an anti-CD22 antibody described herein can be replaced with a different amino acid residue such that the antibody has altered Clq binding and / or reduced or abolished complement dependent cytotoxicity (CDC). This approach is described in further detail in U.S. Patent 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 altered, thereby altering the ability of the antibody to activate complement. This approach is further described in International Publication No. WO 94 / 29351. In some embodiments, the Fc region of an antibody described herein is modified to increase the ability of the antibody to mediate antibody dependent cellular cytotoxicity (ADCC) and / or increase the affinity of the antibody for Fcy receptors. This approach is further described in International Publication No. WO 00 / 42072. In some embodiments, the heavy and / or light chain variable domain sequences of an antibody provided herein can be used to generate, e.g., a CDR-grafted, chimeric, humanized, or composite human antibody or antigen binding fragment, as described elsewhere herein. As will be appreciated by those of ordinary skill in the art, any variant, CDR-grafted, chimeric, humanized, or composite antibody derived from any of the antibodies provided herein can be used in the compositions and methods described herein, and will maintain the ability to specifically bind CD22, such that the variant, CDR-grafted, chimeric, humanized, or composite antibody has at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or more binding to CD22 relative to the original antibody from which it is derived.

[0225] In some embodiments, the antibodies provided herein comprise mutations that confer desirable properties to the antibodies. For example, to avoid potential complications due to Fab-arm exchange that is known to occur with native IgG4 mAbs, the antibodies provided herein can comprise 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 Kabat numbering) is converted to proline, resulting in an IgGl-like hinge sequence. Thus, any of the antibodies can include the stabilizing "Adair" mutation.

[0226] In some embodiments, the antibody is modified, e.g., modified 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 is conjugated to the antibody via N-glycosylation, O-glycosylation, C-glycosylation, glycosylphosphatidylinositolization (GPI anchor attachment), and / or phosphoglycosylation. In some embodiments, the one or more sugar or carbohydrate molecules is a monosaccharide, disaccharide, oligosaccharide, or polysaccharide. In some embodiments, the one or more sugar or carbohydrate molecules is a branched oligosaccharide or branched polysaccharide. In some embodiments, the one or more sugar or carbohydrate molecules comprises 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, there are about 1-10, about 1-5, about 5-10, about 1-4, about 1-3, or about 2 sugar molecules. In some embodiments, the glycosylated antibody is fully or partially glycosylated. In some embodiments, the antibody is glycosylated by chemical reaction or by enzymatic means. In some embodiments, the antibody is glycosylated in vitro or in a cell, which can optionally lack enzymes in the N- or O-glycosylation pathway, e.g., glycosyltransferases. In some embodiments, the antibody is functionalized with a sugar or carbohydrate molecule as described in International Patent Application Publication WO 2014065661, published May 1, 2014, entitled "Modified antibody, antibody-conjugate and process for the preparation thereof".

[0227] In some embodiments, any of the anti-CD22 antibodies described herein can 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 of the VH and VL sequences described herein, any of the IgG heavy and light chain sequences, or any of the F(ab’) heavy and light chain sequences, and further comprise a signal peptide (e.g., an N-terminal signal peptide).

[0228] In some embodiments, any of the antibodies described herein is a multispecific antibody that specifically binds CD22 and one or more additional target antigens. In some embodiments, the antibody is a bispecific antibody that specifically binds CD22 and one additional target antigen. In some embodiments, the multispecific antibody 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.

[0229] 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 capable of modulating 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 or chemotherapeutic agent. In some embodiments, the antibodies described herein are directly or indirectly conjugated to a detectable label, e.g., for diagnostic purposes.

[0230] In some embodiments, the present disclosure also provides fusion proteins comprising the anti-CD22 antibodies described herein fused directly or indirectly (e.g., via a linker) to one or more polypeptides or proteins. (b) Chimeric antigen receptors

[0231] In some aspects, the present disclosure also contemplates engineering any anti-CD22 antibody as an 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 an extracellular ligand binding domain. In some embodiments, the ligand binding domain binds to a cell surface marker on a target cell (e.g., a 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 a B cell in a B cell disorder). 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)), otherwise referred to herein as a ligand binding domain (also referred to herein as an 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 a 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 an HC CDR1, an HC CDR2, and an HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 7, 55, 69, or 83. Alternatively or additionally, an anti-CD22 CAR comprises an LC CDR1, an LC CDR2, and an LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 8, 56, 70, or 84.In some embodiments, the anti-CD22 CAR comprises: (i) HC CDR1, HC CDR2, and HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 7, and LC CDR1, LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 8; (ii) HC CDR1, HC CDR2, and HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 55, and LC CDR1, LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 56; (iii) HC CDR1, HC CDR2, and HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 69, and LC CDR1, LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 70; or (iv) HC CDR1, HC CDR2, and HC CDR3 of a heavy chain variable domain (VH) having the amino acid sequence of SEQ ID NO: 83, and LC CDR1, LC CDR2, and LC CDR3 of a light chain variable domain (VL) having the amino acid sequence of SEQ ID NO: 84.

[0232] In some embodiments, the anti-CD22 CAR comprises a HC CDR3 having an amino acid sequence of SEQ ID NO: 3, 51, 65, or 79 according to the Kabat definition system. In some embodiments, according to the Kabat definition system, the anti-CD22 CAR comprises (i) a HC CDR1 having an amino acid sequence of SEQ ID NO: 1, a HC CDR2 having an amino acid sequence of SEQ ID NO: 2, and a HC CDR3 having an amino acid sequence of SEQ ID NO: 3; (ii) a HC CDR1 having an amino acid sequence of SEQ ID NO: 49, a HC CDR2 having an amino acid sequence of SEQ ID NO: 50, and a HC CDR3 having an amino acid sequence of SEQ ID NO: 51; (iii) a HC CDR1 having an amino acid sequence of SEQ ID NO: 63, a HC CDR2 having an amino acid sequence of SEQ ID NO: 64, and a HC CDR3 having an amino acid sequence of SEQ ID NO: 65; or (iv) a HC CDR1 having an amino acid sequence of SEQ ID NO: 63, a HC CDR2 having an amino acid sequence of SEQ ID NO: 78, and a HC CDR3 having an amino acid sequence of SEQ ID NO: 79. Alternatively or additionally, in some embodiments, according to the Kabat definition system, the anti-CD22 CAR comprises (i) a LC CDR1 having an amino acid sequence of SEQ ID NO:4, a LC CDR2 having an amino acid sequence of SEQ ID NO:5, and a LC CDR3 having an amino acid sequence of SEQ ID NO:6; (ii) a LC CDR1 having an amino acid sequence of SEQ ID NO:52, a LC CDR2 having an amino acid sequence of SEQ ID NO:53, and a LC CDR3 having an amino acid sequence of SEQ ID NO:54; (iii) a LC CDR1 having an amino acid sequence of SEQ ID NO:66, a LC CDR2 having an amino acid sequence of SEQ ID NO:67, and a LC CDR3 having an amino acid sequence of SEQ ID NO:68; or (iv) a LC CDR1 having an amino acid sequence of SEQ ID NO:80, a LC CDR2 having an amino acid sequence of SEQ ID NO:81, and a LC CDR3 having an amino acid sequence of SEQ ID NO:82.In some embodiments, 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; 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, according to the Kabat definition system.

[0233] In some embodiments, the anti-CD22 CAR comprises an HC CDR1, an HC CDR2, and an HC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) 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 additionally, the anti-CD22 CAR comprises an LC CDR1, an LC CDR2, and an LC CDR3 that collectively contain no more than 5 amino acid variations (e.g., no more than 5, 4, 3, 2, or 1 amino acid variations) 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.

[0234] In some embodiments, the anti-CD22 CAR comprises an HC CDR1, an HC CDR2, and an HC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical 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 additionally, the anti-CD22 CAR comprises an LC CDR1, an LC CDR2, and an LC CDR3 that collectively are at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical 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.

[0235] In some embodiments, the anti-CD22 CAR comprises: (i) an HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 1, an HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and / or an HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) an HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 49, an HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 50, and / or an HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 51; (iii) an HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and / or an HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 65; or (iv) an HC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR1 having the amino acid sequence of SEQ ID NO: 63, an HC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or an HC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to an HC CDR3 having the amino acid sequence of SEQ ID NO: 79.Alternatively or additionally, the anti-CD22 CAR comprises: (i) an LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR1 having the amino acid sequence of SEQ ID NO: 4, an LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or an LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) an LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR1 having the amino acid sequence of SEQ ID NO: 52, an LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR2 having the amino acid sequence of SEQ ID NO: 53, and / or an LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR3 having the amino acid sequence of SEQ ID NO: 54; (iii) an LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR1 having the amino acid sequence of SEQ ID NO: 66, an LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and / or an LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR3 having the amino acid sequence of SEQ ID NO: 68; or (iv) an LC CDR1 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR1 having the amino acid sequence of SEQ ID NO: 80, an LC CDR2 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or an LC CDR3 having no more than 3 amino acid variations (e.g., no more than 3, 2, or 1 amino acid variations) compared to the LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0236] In some embodiments, the anti-CD22 CAR comprises: (i) a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 1, a HC that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 2, and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 3; (ii) a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 49, a HC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 50; (iii) a HC CDR1 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR1 having the amino acid sequence of SEQ ID NO: 63, a HC at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and / or a HC CDR3 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 51; (iv) a HC CDR1 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 64, and / or a HC CDR3 having the amino acid sequence of SEQ ID NO: 65. or (iv) a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 63, a HC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR2 having the amino acid sequence of SEQ ID NO: 78, and / or a HC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a HC CDR3 having the amino acid sequence of SEQ ID NO: 79.Alternatively or additionally, the anti-CD22 CAR comprises: (i) a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 4, a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 5, and / or a LC CDR3 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 6; (ii) a LC CDR1 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 52, a LC CDR2 that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 53. (iii) a LC CDR1 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 66, a LC CDR2 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and / or a LC CDR3 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 54; (iv) a LC CDR1 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 66, a LC CDR2 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 67, and / or a LC CDR3 having the amino acid sequence of SEQ ID NO: 68. or (iv) a LC CDR1 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR1 having the amino acid sequence of SEQ ID NO: 80, a LC CDR2 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR2 having the amino acid sequence of SEQ ID NO: 81, and / or a LC CDR3 at least 80% (e.g., 80%, 85%, 90%, 95%, 98% or 99%) identical to a LC CDR3 having the amino acid sequence of SEQ ID NO: 82.

[0237] 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 having 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.

[0238] In some embodiments, the anti-CD22 CAR comprises a VH that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VH set forth in any one of SEQ ID NOs: 7, 55, 69, and 83. Alternatively or additionally, the anti-CD22 CAR comprises a VL that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VL set forth in any one of SEQ ID NOs: 8, 56, 70, and 84. In some embodiments, the anti-CD22 CAR comprises a VH that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VH set forth in SEQ ID NO: 7 and a VL that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VL set forth in SEQ ID NO: 8. In some embodiments, the anti-CD22 CAR comprises a VH that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VH set forth in SEQ ID NO: 55 and a VL that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VL set forth in SEQ ID NO: 56. In some embodiments, the anti-CD22 CAR comprises a VH that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VH set forth in SEQ ID NO: 69 and a VL that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variation) compared to the VL set forth in SEQ ID NO: 70.In some embodiments, the anti-CD22 CAR comprises a VH that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VH set forth in SEQ ID NO: 83 and a VL that contains no more than 20 amino acid variations (e.g., no more than 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 9, 8, 7, 6, 5, 4, 3, 2, or 1 amino acid variations) compared to the VL set forth in SEQ ID NO: 84.

[0239] In some embodiments, the anti-CD22 CAR comprises a VH that comprises 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 any one of SEQ ID NOs: 7, 55, 69, and 83. Alternatively or additionally, the anti-CD22 CAR comprises a VL that comprises 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 any one of SEQ ID NOs: 8, 56, 70, and 84. In some embodiments, the anti-CD22 CAR comprises a VH that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VH set forth in SEQ ID NO: 7 and a VL that is at least 80% (e.g., 80%, 85%, 90%, 95%, 98%, or 99%) identical to the VL set forth in SEQ ID NO: 8. In some embodiments, the anti-CD22 CAR comprises a VH that is 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 that is 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, the anti-CD22 CAR comprises a VH that is 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 that is 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 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 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.

[0240] 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 to 10 amino acids, 5 to 20 amino acids, 10 to 30 amino acids, 20-50 amino acids, 40 to 60 amino acids, 60 to 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 by U.S. Patent Nos. 8,445,251 and 9,434,931.

[0241] In some embodiments, the anti-CD22 CAR comprises an extracellular ligand binding domain comprising a scFv comprising a VH and a VL, and the C-terminus of the VH is connected to the N-terminus of the VL via a linker. In some embodiments, the anti-CD22 CAR comprises an extracellular ligand binding domain comprising a scFv comprising a VH and a VL, and the C-terminus of the VL is connected to the N-terminus of the VH via a linker. In some embodiments, the anti-CD22 CAR of the disclosure further comprises a hinge region. Any suitable known hinge region can be used in the anti-CD22 CAR described herein, for example, a hinge region derived from CD4, CD8, CD28, CD3, IgGl, IgG4, IgD, IgA, or IgM, hybrids or variants thereof (see, e.g., Jayaraman et al., CAR-T design: Elements and their synergistic function, eBioMedicine, vol. 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).

[0242] In some embodiments, the anti-CD22 CAR of the present disclosure further comprises a transmembrane domain that links the extracellular ligand-binding domain to the intracellular signaling and costimulatory domains. With respect to the transmembrane domain, the CAR can be designed to comprise a transmembrane domain that is fused directly to the extracellular domain (e.g., antigen-binding domain) of the CAR, or via a hinge region. The use of any transmembrane domain is contemplated herein, so long as the domain is capable of anchoring the CAR comprising the domain to the cell membrane. In some embodiments, a transmembrane domain that naturally associates with one of the domains in the CAR is used. In some cases, the transmembrane domain can be selected or modified by amino acid substitution to prevent such domains from associating with transmembrane domains of the same or different surface membrane proteins to minimize interactions with other members of the receptor complex. Those skilled in the art will appreciate that the complete transmembrane domain or portions thereof are implemented with the cytoplasmic domain or portions thereof. The transmembrane domain can be derived from natural or synthetic sources. In the case where the source is natural, the domain can be derived from any membrane-bound or transmembrane protein. In some embodiments, the transmembrane domain can be synthetic, in which case it will comprise primarily hydrophobic residues such as leucine and valine. Preferably, a phenylalanine, tryptophan, and valine triad will be found at each end of the synthetic transmembrane domain. Optionally, a short oligo- or polypeptide linker, preferably 2 to 10 amino acids in length, can form a junction between the transmembrane domain and the cytoplasmic signaling domain of the CAR. A glycine-serine diad provides a particularly suitable linker. In some embodiments, the transmembrane domain can be any suitable transmembrane domain known in the art, for example, a transmembrane domain derived from TCRa, TCRP, TCRz, CD3z, CD3e, CD3y, CD3d, 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, the use of any transmembrane domain is contemplated herein, so long as the domain is capable of anchoring the CAR comprising the extracellular domain to the cell membrane. The transmembrane domain can be identified using any method known in the art or described herein, for example, by using the UniProt database.

[0243] In some embodiments, the anti-CD22 CAR further comprises an intracellular (or cytoplasmic) domain. In some embodiments, the intracellular domain of the CAR is responsible for activating at least one normal effector function of the immune cell into which the CAR has been placed. The term “effector function” refers to a specialized function of a cell (e.g., a T cell, NK cell, or NKT cell). For example, an effector function of a cell (e.g., a T cell, NK cell, or NKT cell) can be cytolytic activity or helper activity, including secretion of cytokines. The term “intracellular signaling domain” thus refers to the portion of a protein that transduces the effector function signal and directs the cell to perform a specialized function. While it is possible to employ the entire intracellular signaling domain, in many cases it is not necessary to use the entire domain. In terms of using a truncated portion of the intracellular signaling domain, such truncated portions can be used in place of the full domain so long as it transduces the effector function signal. The term intracellular signaling domain is thus 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 the chimeric antigen receptors as disclosed herein can include, but are 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 CD3 zeta intracellular domain, a CD3 gamma intracellular domain, a CD3 delta intracellular domain, a CD3 epsilon intracellular domain, and a CD7 intracellular domain, and a CD22 intracellular domain.

[0244] In some embodiments, the intracellular domain further comprises one or more intracellular costimulatory domains, such as those described herein, that deliver a costimulatory signal that promotes cell proliferation, cell survival, and / or cytokine secretion following binding of the extracellular domain. In some embodiments, such intracellular costimulatory domains include, but are not limited to, any of the costimulatory domains disclosed herein or those known in the art, including but not limited to CD28, ICOS, 4-1BB, OX40, or CD27.

[0245] The intracellular signaling domain of the chimeric antigen receptors of the present disclosure is responsible for activating at least one normal effector function of the cell into which the CAR has been placed and / or activating proliferation and cell survival pathways.

[0246] It will be appreciated that the chimeric antigen receptors as disclosed herein can include a domain (e.g., an extracellular domain, a transmembrane domain, an intracellular (cytoplasmic) domain, a costimulatory domain, a signaling domain, or any combination thereof) having a sequence described herein, or a variant thereof, or a fragment thereof (e.g., a variant and / or fragment that retains a function required for chimeric antigen receptor activity) of any one or more domains disclosed herein. III. Preparation of Anti-CD22 Antibodies

[0247] Antibodies capable of binding CD22 as described herein can be prepared by any method known in the art. See, e.g., Harlow and Lane, (1998) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, New York.

[0248] In some embodiments, antibodies specific for a target antigen (e.g., CD22) can be prepared by conventional hybridoma technology. Full-length target antigen or fragments thereof, optionally conjugated to a carrier protein such as KLH, can be used to immunize a host animal to produce antibodies that bind to the antigen. The routes and schedules of immunization of the host animal are generally consistent with established conventional techniques for antibody stimulation and production as further described herein. General techniques for the production of mouse, humanized, and human antibodies are known in the art and described herein. It is contemplated that any mammalian subject including a human or antibody producing cells therefrom can be manipulated to serve as the basis for the production of mammalian, including human, hybridoma cell lines. Typically, a host animal is inoculated intraperitoneally, intramuscularly, orally, subcutaneously, footpad, and / or intradermally with an amount of an immunogen, including the immunogens described herein, coupled optionally to a carrier protein.

[0249] If desired, a target antibody (monoclonal or polyclonal) (e.g., produced by a hybridoma) can be sequenced and the polynucleotide sequence can be cloned into a vector for expression or propagation. The sequence encoding the target antibody can be maintained in the vector of the host cell, which can then be expanded and frozen for future use. In the alternative, the polynucleotide sequence can be used for genetic manipulation to "humanize" the antibody or to improve the affinity (affinity maturation) or other characteristics of the antibody. For example, the constant region can be engineered to more closely resemble a human constant region to avoid an immune response when the antibody is used for clinical trials and human therapy. It can be desirable to genetically manipulate the antibody sequence to obtain greater affinity and greater efficacy for the target antigen. It will be apparent to those skilled in the art that one or more polynucleotide changes can be made to the antibody and still maintain its binding specificity for the target antigen.

[0250] In other embodiments, fully human antibodies can be obtained by using commercially available mice that have been engineered to express specific human immunoglobulin proteins. Transgenic animals designed to produce a more desired (e.g., fully human antibodies) or stronger immune response can also be used to generate humanized antibodies or human antibodies. Examples of such technologies are XenomouseRTMfrom Amgen, Inc. (Fremont, CA) and HuMAb-MouseRTMand TC MouseTMfrom Medarex, Inc. (Princeton, NJ) or H2L2 mice from Harbour Antibodies BV (Holland). In another alternative, antibodies can be recombinantly produced 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.

[0251] Antigen-binding fragments of intact antibodies (full length antibodies) can be produced by conventional methods. For example, F(ab')2 fragments can be generated by pepsin digestion of an antibody molecule, 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 via, for example, conventional recombinant techniques. In one example, DNA encoding a monoclonal antibody specifically immunoreactive against a target antigen can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are specific to the heavy and light chain genes of the monoclonal antibody). Hybridoma cells serve as a preferred source of such DNA. Once isolated, the DNA can be placed into one or more expression vectors, which can then be introduced into a host cell such as E. coli, simian COS cells, Chinese hamster ovary (CHO) cells, human HEK293 cells, or myeloma cells to obtain the synthesis of monoclonal antibodies in recombinant host cells. See, e.g., PCT Publication No. WO 87 / 04462. The DNA can then be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences, Morrison et al., (1984) Proc. Nat. Acad. Sci. 81 :6851, or by covalent joining of all or a portion of the coding sequence to the coding sequence of a non-immunoglobulin polypeptide. In this manner, genetically engineered antibodies, such as “chimeric” or “hybrid” antibodies, can be produced; these antibodies have the target antigen binding specificity of the original antibody.

[0252] Single-chain antibodies can be prepared by recombinant techniques by linking a nucleotide sequence encoding the variable region of the heavy chain and a nucleotide sequence encoding the variable region of the light chain. Preferably, a flexible linker is incorporated between the two variable regions.

[0253] Alternatively, techniques described (U.S. Patent Nos. 4,946,778 and 4,704,692) for the production of single-chain antibodies can be adapted to produce phage or yeast scFv libraries, and scFv clones specific for CD22 can be identified from the libraries following conventional procedures. Positive clones can be further screened to identify those clones with high CD22 binding affinity.

[0254] Antibodies obtained according to methods known in the art and described herein can be characterized using methods well known in the art. For example, one method is to identify the epitope to which the antibody binds, or "epitope mapping." Numerous methods are known in the art for mapping and characterizing the location of an epitope on a protein, including solving the crystal structure of an antibody-antigen complex, competition 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, N.Y., 1999. In one example, epitope mapping can be accomplished using H / D-Ex (hydrogen deuterium exchange) in combination with proteolysis and mass spectrometry. In another example, epitope mapping can be used to determine the sequence to which an antibody binds. An epitope can be a linear epitope, i.e., contained in a single stretch of amino acids, or a conformational epitope formed by three-dimensional interactions of amino acids that are not necessarily contained in a single stretch (primary structure linear sequence). Peptides of varying lengths (e.g., at least 4-6 amino acids long) can be isolated or synthesized (e.g., recombinantly) and used in binding assays with the antibody. In another example, the epitope to which an antibody binds can be determined in a systematic screen by using overlapping peptides derived from the sequence of the target antigen and determining binding of the antibody. According to a gene fragment expression assay, an open reading frame encoding a target antigen is fragmented randomly or by specific genetic construction, and the reactivity of expressed antigen fragments with a test antibody is determined. For example, gene fragments can be generated by PCR and then transcribed and translated into proteins in vitro in the presence of radioactive amino acids. Binding of the antibody to the radiolabeled antigen fragments is then determined by immunoprecipitation and gel electrophoresis. Certain epitopes can also be identified by using a library of large random peptide sequences displayed on the surface of bacteriophage particles (phage libraries). Alternatively, a defined library of overlapping peptide fragments can be tested for binding to a test antibody in a simple binding assay. In another example, mutagenesis of the antigen binding domain, domain swap experiments, and alanine scanning mutagenesis can be performed to identify residues required, sufficient, and / or essential for epitope binding. Alternatively, competition assays can be performed using other antibodies known to bind 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.

[0255] In some examples, the anti-CD22 antibodies are prepared by recombinant techniques as exemplified below. Nucleic acids encoding the heavy and light chains of an anti-CD22 antibody as described herein can be cloned into one expression vector, each nucleotide sequence operably linked to a suitable promoter. In one example, each nucleotide sequence encoding the heavy and light chains is operably linked to a different 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 desired, an internal ribosome entry site (IRES) can be inserted between the heavy and light chain-encoding sequences.

[0256] In some examples, the nucleotide sequences encoding the two chains of an antibody are cloned into two vectors, which can be introduced into the same or different cells. When the two chains are expressed in different cells, each of the chains can be isolated from the host cells expressing them, and the isolated heavy and light chains can be mixed and incubated under suitable conditions that allow the antibody to form.

[0257] Generally, the nucleic acid sequences encoding one or all chains of an antibody can be cloned into a suitable expression vector in operable linkage with a suitable promoter using methods known in the art. For example, the nucleotide sequences and the vector can be contacted with restriction enzymes under suitable conditions to produce complementary ends on each molecule that can pair with each other and be ligated with a ligase. Alternatively, synthetic nucleic acid linkers can be attached to the ends of the genes. These synthetic linkers contain nucleic acid sequences that correspond to specific restriction sites in the vector. The choice of expression vector / promoter will depend on the type of host cell used to produce the antibody.

[0258] 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, E. coli lac UV promoter, and herpes simplex virus tk promoter.

[0259] Regulatable promoters can also be used. Such regulatable promoters include promoters that use the lac repressor from E. coli as a transcriptional regulator to regulate transcription from mammalian cell promoters carrying the lac operon [Brown, M. et al., Cell, 49:603-612 (1987)], promoters that use 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 using estradiol, RU486, diphenolmurislerone, or rapamycin, VP16, or p65. Inducible systems are available from, among others, Invitrogen, Clontech, and Ariad.

[0260] Regulatable promoters including repressors with operators can be used. In one embodiment, the lac repressor from E. coli can function as a transcriptional regulator to modulate transcription from a mammalian cell promoter carrying the lac operator [[M. Brown et al., Cell, 49:603-612 (1987)]; Gossen and Bujard (1992); [[M. Gossen et al., Natl. Acad. Sci. USA, 89:5547-5551 (1992)]], the tetracycline repressor (tetR) in combination with a transcriptional activator (VP 16) to generate a tetR-mammalian cell transcriptional activator fusion protein, tTa (tetR-VP 16), with a minimal promoter carrying tetO derived from the human cytomegalovirus (hCMV) promoter to generate a tetR-tet operator system to control gene expression in mammalian cells. In one embodiment, a tetracycline-inducible switch is used. When the tetracycline operator is positioned correctly downstream of the TATA element of the CMV IE promoter, the tetracycline repressor (tetR) alone, rather than the tetR-mammalian cell transcription factor fusion derivative, can function as an effective transregulator to modulate gene expression in mammalian cells (Yao et al., Human Gene Therapy). A particular advantage of this tetracycline-inducible switch is that it does not require the use of tetracycline repressor-mammalian cell transactivator or repressor fusion proteins to achieve its regulatable effect, which in some cases can be toxic to cells (Gossen 5 et al., Natl. Acad. Sci. USA, 89:5547-5551 (1992); Shockett et al., Proc. Natl. Acad. Sci. USA, 92:6522-6526 (1995)).

[0261] Additionally, the vector can contain some or all of the following, for example: a selectable marker gene, such as a neomycin gene for selection of stably or transiently transfected mammalian cells; an enhancer / promoter sequence from the immediate early gene of human CMV for high levels of transcription; a transcription termination and RNA processing signal from SV40 for mRNA stability; the SV40 polyomavirus origin of replication and ColEl for proper episomal replication; an internal ribosome binding site (IRES), a universal polylinker; 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 that can be used in practicing 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.

[0262] One or more vectors (e.g., expression vectors) comprising nucleic acids encoding any of the antibodies (e.g., nucleic acid encoding sequences listed in Table 3) can be introduced into a suitable host cell to produce the antibody. Non-limiting examples of host cells include Chinese hamster ovary (CHO) cells, dhfr- CHO cells, human embryonic kidney (HEK)-293 cells, vero cells, non-secreting (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 (COS) cells transformed by SV40. In some embodiments, the host cell expressing an anti-CD22 antibody is a CHO cell. The host cell can be cultured under suitable conditions for expression of the antibody or any polypeptide chain thereof. Such antibody or polypeptide chain thereof can be recovered from the cultured cells (e.g., from the cells or culture supernatant) via conventional methods (e.g., affinity purification). If necessary, the polypeptide chains of the antibody can be incubated under suitable conditions for a suitable period of time to allow production of the antibody. In some embodiments, the host cell comprises a nucleic acid encoding a heavy chain of an anti-CD22 antibody. In some embodiments, the host cell comprises a nucleic acid encoding a light chain of an anti-CD22 antibody. In some embodiments, the host cell comprises a nucleic acid encoding a heavy chain and a nucleic acid encoding a light chain.

[0263] In some embodiments, a method of making an antibody described herein comprises a recombinant expression vector encoding the heavy and light chains of the anti-CD22 antibody, as described herein. The recombinant expression vector can be introduced into a suitable host cell (e.g., a dhfr- CHO cell) by conventional methods, e.g., calcium phosphate-mediated transfection. Positively transformed host cells can be selected and cultured under suitable conditions that allow for expression of the two polypeptide chains of the antibody, which can be recovered from the cells or from the culture medium. If necessary, the two chains recovered from the host cells can be incubated under suitable conditions that allow for the antibody to form.

[0264] In one example, two recombinant expression vectors are provided, one encoding the heavy chain of the anti-CD22 antibody and the other encoding the light chain of the anti-CD22 antibody. Both recombinant expression vectors can be introduced into a suitable host cell (e.g., a dhfr- CHO cell) by conventional methods, e.g., calcium phosphate-mediated transfection.

[0265] Alternatively, each expression vector can be introduced into a suitable host cell. Positively transformed host cells can be selected and cultured under suitable conditions that allow for expression of the antibody polypeptide chains. When both expression vectors are introduced into the same host cell, the antibody produced therein can be recovered from the host cell or from the culture medium. If necessary, the polypeptide chains can be recovered from the host cell or from the culture medium and then incubated under suitable conditions that allow for the antibody to form. When the two expression vectors are introduced into different host cells, each expression vector can be recovered from the corresponding host cell or from the corresponding culture medium. The two polypeptide chains can then be incubated under suitable conditions that allow for the antibody to form.

[0266] Standard molecular biology techniques are used to prepare the recombinant expression vectors, transfect the host cells, select for transformed cells, culture the host cells, and recover the antibody from the culture medium. For example, some antibodies can be isolated from the culture medium using protein A or protein G coupled matrices on affinity chromatography.

[0267] Any nucleic acid encoding a heavy chain, a light chain, or both, of an anti-CD22 antibody as described herein (e.g., as provided in Table 3), a vector (e.g., an expression vector) containing the nucleic acid; and a host cell comprising the vector are within the scope of the present disclosure. Table 3: Nucleic acid sequences encoding the VH / VL of the anti-CD22 antibodies listed in Table 1.

[0268] 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 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, and 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.

[0269] 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 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, and a 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.

[0270] In some embodiments, the disclosure provides expression vectors encoding 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, 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. 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: 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.

[0271] In some embodiments, the anti-CD22 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.

[0272] In some embodiments, the anti-CD22 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.

[0273] In some embodiments, an anti-CD22 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.

[0274] In some embodiments, an anti-CD22 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: 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, the present disclosure provides a recombinant cell expressing an anti-CD22 antibody described herein (e.g., a recombinant cell for producing the antibody).

[0276] Accordingly, the present disclosure provides a method for producing the antibody, the method comprising culturing a recombinant cell under conditions suitable for the expression of the antibody from an expression vector by the recombinant cell. The recombinant cell expressing the antibody can 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 cell or cells are cultured using any suitable known method in the art. IV. Pharmaceutical Compositions

[0277] The antibodies as described herein, and the encoding nucleic acids or nucleic acid collections, vectors comprising these nucleic acids or nucleic acid collections, or host cells comprising these vectors can be mixed with a pharmaceutically acceptable carrier (excipient) to form a pharmaceutical composition for treating a disease of interest. By "acceptable" it is meant that the carrier must be compatible with the active ingredient of the composition (and preferably, capable of stabilizing the active ingredient) and not deleterious to the subject to be treated. Pharmaceutically acceptable excipients (carriers) include buffers well known in the art. See, e.g., Remington: The Science and Practice of Pharmacy 20th Ed. (2000) Lippincott Williams and Wilkins, K. E. Hoover, Ed.

[0278] The anti-CD22 antibody-containing pharmaceutical compositions disclosed herein can further comprise a suitable buffer. A buffer is a weak acid or base used to maintain the pH of a solution close to a chosen value upon the addition of another acid or base. In some examples, the buffer disclosed herein can be a buffer capable of maintaining physiological pH regardless of changes in carbon dioxide concentration (produced by cellular respiration). Exemplary buffers include, but are not limited to, HEPES (4-(2-hydroxyethyl)-l-piperazineethanesulfonic acid) buffer, Dulbecco's phosphate buffered saline (DPBS) buffer, or phosphate buffered saline (PBS) buffer. Such buffers can comprise disodium hydrogen phosphate and sodium chloride, or potassium dihydrogen phosphate and potassium chloride.

[0279] In some embodiments, the buffer in the pharmaceutical compositions described herein can maintain a pH of about 5-8. For example, the pH of the pharmaceutical composition can 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 pH of the pharmaceutical composition can be less than 7, for example, about 7, 6.8, 6.5, 6.3, 6, 5.8, 5.5, 5.3, or 5.

[0280] The pharmaceutical compositions described herein comprise one or more suitable salts. Salts are ionic compounds that can be formed by the neutralization reaction of acids and bases. (Skoog, D. A; West, D. M.; Holler, J. F.; Crouch, S. R. (2004). "Chapters 14-16". Fundamentals of Analytical Chemistry (8th ed.).). Salts consist of an associated number of cations (positively charged ions) and anions (negative ions) such that the product is electrically neutral (no net charge).

[0281] In some embodiments, the pharmaceutical composition can include a pharmaceutically acceptable carrier, excipient, or stabilizer in lyophilized formulation or 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 can be formulated for intravenous injection. In some embodiments, the pharmaceutical composition can be formulated for subcutaneous injection.

[0282] Pharmaceutical compositions intended for in vivo administration must be sterile. This is readily accomplished, for example, by filtration through sterile filtration membranes. Therapeutic antibody compositions are generally placed into a container having a sterile access port, for example, an intravenous or subcutaneous solution bag or vial having a stopper pierceable by a hypodermic injection needle. V. Methods of use

[0283] Aspects of the present disclosure relate to compositions and methods for treating a B-cell disorder and / or one or more conditions caused by a B-cell disorder in a subject.

[0284] In some aspects, the present disclosure features a method for treating a B-cell disorder, the method 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) any one or more antibodies or antigen-binding fragments thereof described herein (including conjugates), (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 nucleic acids described herein; (v) any one or more expression vectors described herein; (vi) any one or more recombinant cells described herein; (vii) any one or more isolated polypeptides described herein; and / or (viii) any one or more pharmaceutical compositions described herein.

[0285] In some embodiments, the B-cell disorder is an autoimmune disease, such as wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), myasthenia gravis, Graves’ disease, or immune thrombocytopenic purpura (ITP).

[0286] In some embodiments, the B-cell disorder is a cancer. The cancer can be, for example, a B-cell lymphoma, such as a non-Hodgkin lymphoma. The non-Hodgkin lymphoma can be, for example, Burkitt lymphoma, chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma.

[0287] In yet another aspect, the disclosure features a method for preventing, reducing, delaying, or inhibiting the proliferation and / or growth of a cancer cell, comprising contacting the cancer cell with a therapeutic agent that binds to CD22 expressed on the surface of the cancer cell, wherein the therapeutic agent is: (i) any one or more antibodies or antigen-binding fragments thereof described herein (including conjugates), (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.

[0288] In certain embodiments, the therapeutic agent can be administered by injection via intravenous, intraperitoneal, intracerebral (intraparenchymal), intracerebroventricular, intramuscular, subcutaneous, intraocular, intraarterial, intraportal, or intralesional routes; by sustained release systems, or by implantation devices. In certain embodiments, the compositions can be administered by bolus injection or continuously by infusion or by implantation devices.

[0289] Based on the teachings provided herein, it will be evident to one of ordinary skill in the art to determine an amount of an antibody (e.g., an anti-CD22 antibody) that is effective for a therapeutic purpose. As one of ordinary skill in the art will recognize, the effective amount varies depending on the particular condition being treated, the severity of the condition, individual patient parameters including age, physical condition, size, gender, and weight, the duration of the treatment, the nature of concurrent therapy (if any), the specific route of administration and like factors within the knowledge and expertise of the health practitioner. The specific dose regimen, i.e., dosing amounts, timing, and repetition, for use in the methods described herein will depend on the particular subject and that subject’s medical history as described herein.

[0290] Empirical considerations, such as the time of onset of maximum effect, half-life, and / or the time above a particular concentration, will generally help determine the dosage. For example, antibodies that are compatible with the human immune system, such as humanized antibodies or fully human antibodies, can be used to extend the half-life of the antibody and prevent the antibody from being attacked by the immune system of the host. 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. The frequency of administration can be determined and adjusted during the course of therapy, and is generally, but not necessarily, based on the treatment and / or inhibition and / or amelioration and / or delay of the target disease / condition. Alternatively, a sustained continuous release formulation of the antibody can be appropriate. Various formulations and devices for achieving sustained release are known in the art.

[0291] The frequency of administration can vary depending on the claimed method. In some embodiments, the composition can be administered once. In some embodiments, the composition will be administered multiple times. In some embodiments, the frequency of administration is every week, 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 longer. In some embodiments, the composition is administered daily, every two weeks, every week, every two months, every month, or at any interval that provides suitable (e.g., maximal) efficacy while minimizing the safety risks to the subject. In general, efficacy and treatment, as well as safety risks, can be monitored throughout the course of treatment.

[0292] In some embodiments, a composition provided herein (e.g., an anti-CD22 antibody) can be administered to a subject at one or more intervals during a set period of time. In some cases, the period of time during which a composition is administered to a subject at one or more intervals can be separated by a period of time during which the subject is not administered the composition. In some embodiments, the relative duration of each period of time can depend on the subject’s response to treatment or the severity of the disease or both and / or can be determined based on the judgment of the treating physician.

[0293] In some embodiments, the antibody can be administered parenterally. For example, a parenterally administered composition can be administered subcutaneously, intradermally, intravenously, intraperitoneally, intratumorally, intramuscularly, intraarticularly, intraarterially, or by infusion techniques. Additionally, it can be administered to the subject via an injectable depot route of administration, such as using 1, 3, or 6 month depot injectable or biodegradable materials and methods.

[0294] In some embodiments, the antibody (e.g., an anti-CD22 antibody) is administered intravenously. In some embodiments, the antibody (e.g., an anti-CD22 antibody) is administered subcutaneously.

[0295] For intravenous injection, a water-soluble antibody can be administered by a drip method, whereby a pharmaceutical preparation containing the antibody and a physiologically acceptable excipient is infused. The physiologically acceptable excipient can include, for example, 5% dextrose, 0.9% saline, Ringer’s solution, or other suitable excipients. Other injectable compositions can contain various carriers such as vegetable oils, dimethylacetamide, dimethylformamide, ethyl lactate, ethyl carbonate, isopropyl myristate, ethanol, and polyols (glycerol, propylene glycol, liquid polyethylene glycol, etc.). In some cases, a formulation, e.g., a sterile formulation of a suitable soluble salt form of an antibody, can be dissolved and administered in a pharmaceutical excipient such as water for injection, 0.9% saline, or 5% dextrose solution.

[0296] In one embodiment, the antibody is administered via site-specific or targeted local delivery techniques. Examples of site-specific or targeted local delivery techniques include various implantable reservoir sources of the antibody or local delivery catheters such as infusion catheters, indwelling catheters, or needle catheters, synthetic grafts, epicardial wraps, shunts, and stents or other implantable devices, site-specific carriers, direct injection, or direct application. See, e.g., PCT Publication No. WO 00 / 53211 and U.S. Patent No. 5,981,568.

[0297] In some embodiments, more than one antibody or a combination of an antibody with another suitable therapeutic agent can be administered to a subject in need of treatment. Antibodies can also be used in conjunction with other agents for enhancing and / or complementing the effectiveness of the agents. The therapeutic efficacy of the targeted disease / condition can be assessed by methods well known in the art.

[0298] Anti-CD22 antibodies and therapeutic methods involving aspects such as those described in the present disclosure can be used in combination with other types of therapies for the targeted diseases or conditions disclosed herein. In this context, the antibody compositions and therapeutic agents can be administered simultaneously or sequentially (in any order). Examples include chemotherapy, immunotherapy, surgery, radiation, gene therapy, etc., or anti-infective therapies. Such therapies can be administered simultaneously or sequentially (in any order) with the treatments according to the present disclosure.

[0299] For example, combination therapies can include an anti-CD22 antibody and pharmaceutical compositions described herein co-formulated and / or co-administered with at least one additional therapeutic agent. Such combination therapies can advantageously utilize lower dosages of the administered therapeutic agents, thereby preventing possible toxicities or complications associated with various monotherapies.

[0300] 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). Accordingly, in some embodiments, methods of delivering a molecular payload to a subject for therapeutic purposes are provided. In such embodiments, the molecular payload can be a small molecule, a protein, a nucleic acid, an oligonucleotide, or any molecular entity capable of modulating 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 or chemotherapeutic agent.

[0301] Any of the anti-CD22 antibodies disclosed herein can also be used to detect the presence of CD22 in vitro or in vivo. The results obtained from such detection methods can be used for diagnostic purposes (e.g., diagnosing a disease associated with CD22) or for scientific research purposes (e.g., identifying new CD22-secreting cell types, studying biological activity and / or modulating secreted CD22). For assay uses such as diagnostic uses, the anti-CD22 antibodies as 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) in vivo or in vitro.

[0302] In other embodiments, the anti-CD22 antibodies as described herein can be attached to a detectable label, which is a compound capable of directly or indirectly releasing a detectable signal, such that the aptamer can be detected, measured, and / or quantified in vitro or in vivo. Examples of such “detectable labels” 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 to the aptamer directly or indirectly by conventional methods.

[0303] In some embodiments, the detectable label is an agent suitable for in vitro detection of CD22-expressing cells, which can be a radioactive molecule, a radiopharmaceutical, or an iron oxide particle. Radioactive molecules suitable for in vivo imaging include, but are not limited to 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, 213 Bi, 212 Bi, 212 Pb, and 67 Ga. Exemplary radiopharmaceuticals suitable for in vivo imaging include 111 In oxyquinoline, 131 Iodinated sodium, 99 mTc Mebrofenin, and 99 mTc Red blood cells, 123 Iodinated sodium, 99 mTc Exametazime, 99 mTc Macroaggregated albumin, 99mTc Medronate, 99 mTc Mertiatide, 99 mTc Oxidronate, 99 mTc Pentetate, 99 mTc Pertechnetate, 99 mTc Sestamibi, 99 mTc Sulfur Colloid, 99 mTc Tetrofosmin, thallium-201, or xenon-133.

[0304] The reporter can also be a dye, such as a fluorophore, that can be used to detect a disease mediated by CD22-expressing cells in a tissue sample.

[0305] To perform an in vitro diagnostic assay, an anti-CD22 antibody can be contacted with a sample suspected of containing CD22, such as a cell expressing CD22 in a disease microenvironment. The antibody and sample can be incubated under suitable conditions for a suitable period of time to allow the antibody to bind to the CD22 antigen. Such interaction can then be detected via conventional methods, such as ELISA, histological staining, or FACS. To perform an in vivo diagnostic assay, an appropriate amount of an anti-CD22 antibody conjugated to a label (e.g., an imaging agent or a contrast agent) can be administered to a subject in need of examination. The presence of the labeled antibody can be detected by conventional methods based on a signal released from the label.

[0306] To perform a scientific research assay, an anti-CD22 antibody can be used to study the biological activity of CD22, detect the presence of CD22 within a cell, and / or modulate the action of CD22. For example, an appropriate amount of an anti-CD22 can be contacted with a sample suspected of producing CD22, such as a new cell type that has not previously been identified as producing CD22. These cells are permeabilized prior to contacting the anti-CD22 antibody. The antibody and sample can be incubated under suitable conditions for a suitable period of time to allow the antibody to bind to the CD22 antigen. Such interaction can then be detected via conventional methods, such as ELISA, histological staining, or FACS. VI. Kits for therapeutic and diagnostic applications

[0307] The present disclosure also provides kits for therapeutic or diagnostic applications as disclosed herein. Such kits can include one or more containers comprising an anti-CD22 antibody, such as any of those described herein.

[0308] In some embodiments, the kit can include instructions for use according to any of the methods described herein. The instructions included can include a description of administering an anti-CD22 antibody to treat, delay onset of, or ameliorate a disease of interest as described herein. The kit can further include a description of selecting an individual suitable for treatment based on identifying whether the individual has the disease of interest. In yet other embodiments, the instructions include a description of administering the antibody to an individual at risk for the disease of interest.

[0309] Instructions relating to use of an anti-CD22 antibody generally include information as to dosage, schedule of administration, and route of administration for the intended treatment. The containers can be unit doses, bulk packages (e.g., multiple doses packages), or sub-unit doses. The instructions provided in the kits of the application are typically written instructions, e.g., paper sheets inside the kit, but machine-readable instructions, e.g., instructions carried by a magnetic or optical storage disk, are also acceptable.

[0310] The label or package insert indicates that the compositions are used for treating, delaying the onset of, and / or ameliorating a disease or condition. Instructions for practicing any of the methods described herein can be provided.

[0311] The kits of the application are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging, e.g., sealed Mylar or plastic bags, etc.

[0312] Packaging for use in combination with a particular device, such as an infusion device, e.g., a mini-pump, is also contemplated. The kit can have a sterile access port, (for example the container can be a

[0313] The kits can optionally provide additional components such as buffers and explanatory information. Typically, the kit comprises a container and a label or package insert on or associated with the container. In some embodiments, the application provides articles of manufacture comprising the contents of the kits described above.

[0314] Also provided herein are kits for detecting CD22 in a sample. Such kits comprise any of the anti-CD22 antibodies described herein. In some cases, the anti-CD22 antibody can be conjugated to a detectable label described herein. Conjugation or attachment can include covalent or non-covalent bonding and other forms of association, such as, for example, entrapment of one entity on or within another entity, or entrapment of one or both entities on or within a third entity, such as a micelle.

[0315] Alternatively or additionally, the kit can comprise a secondary antibody capable of binding to the anti-CD22 antibody. The kit can further comprise instructions for using the anti-CD22 antibody to detect CD22. Examples Example 1: Screening method. i. SPRi of binding affinity

[0316] Using LSA, with a running buffer of phosphate buffered saline (PBS) at pH 7.40, and with 1% BSA and 0.05% Tween 20 for antibody binding kinetics experiments. Antibodies were captured on anti-human Fc capture chips prepared using HC30M chips (also from Carterra). For kinetics analysis, purified recombinant His-tagged human CD22 was injected at concentrations ranging from 0.076 nM to 500 nM (3-fold serial dilutions) sequentially. For each concentration, association was allowed for 5 minutes, followed by dissociation for 15 minutes. Results were processed and analyzed using Carterra LSA kinetics software. Figures 1A-1D A sensorgram showing the detector response versus time for the interaction between mAb-1-4 and immobilized recombinant human CD22 is provided in FIG. 2.

[0317] The output of the instrument is a sensorgram, which is a plot of the detector response (measured in “resonance units” (RU)) as a function of time. An increase of 1000 RU corresponds to an increase in mass on the sensor surface of approximately 1 ng / mm 2 .

[0318] Kinetic data were referenced to the gap reference point and double referenced to buffer circulation, then globally fitted to a 1 : 1 binding model to determine the apparent association and dissociation kinetic rate constants (ka and kd values). The ratio kd / ka was used to derive the KD value for each antigen / mAb interaction, i.e. KD = kd / ka.

[0319] Binding kinetics for mAb-1-4 are provided in Table 4 below. Table 4. “Rmax” is the maximum SPR signal resulting from the mAb-1-4 / CD22 interaction. “Res SD” refers to the residual standard deviation.

[0320] For the determination of reactivity to cynomolgus CD22, 300 nM of His-tagged cynomolgus 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 a gap reference point and double referenced to buffer circulation, then the reaction after association (nm) was reported. A cutoff reaction for positive binding was determined using isotype controls. Under these conditions, mAb-1 was determined to have cross-reactivity to cynomolgus CD22. ii. Cell binding

[0321] To calculate the EC50 of antibody binding to cells expressing CD22, anti-CD22 antibodies were tested for binding to Raji cells at concentrations ranging from 100 nM to 0.6 pM (3-fold serial dilutions). Cells were then incubated with secondary antibody R-phycoerythrin AffiniPure Goat Anti-Human IgG (Jackson Immunoresearch 109-115-098). Data were acquired on a FACSCanto II (BD). Median fluorescence intensity (MFI) was plotted against the concentration of anti-CD22 antibody. EC50 was derived by fitting to a 4-parameter dose-response curve.

[0322] EC50s for mAb-2-4 are provided in Table 5 below. Table 5. mAb EC50(M) mAb-2 0.11 mAb-3 0.07 mAb-4 0.09 Other embodiments

[0323] All features disclosed in this specification may be combined in any combination. Each feature disclosed in this specification may be replaced by an alternative feature serving the same, equivalent or similar purpose. Thus, unless expressly stated otherwise, each feature disclosed is only an example of a generic series of equivalent or similar features.

[0324] From the above description, one skilled in the art can easily ascertain the essential characteristics of the present application, and without departing from the spirit and scope thereof, can make various changes and modifications of the application to adapt it to various uses and conditions. Thus, other embodiments are also within the scope of the following claims: Equivalents and scope

[0325] In the claims, unless indicated to the contrary or otherwise obvious from the context, articles such as "a," "an," and "the" may mean one or more than one. Unless indicated to the contrary or otherwise obvious from the context, claims or descriptions including "or" between one or more members of the group are considered satisfied if one, more than one, or all of the members of the group are present in, used in, or otherwise related to a given product or method. The invention includes embodiments in which exactly one member of the group is present in, used in, or otherwise related to a given product or method. The invention includes embodiments in which more than one or all of the members of the group are present in, used in, or otherwise related to a given product or method.

[0326] In addition, the present invention encompasses all variations, combinations and arrangements in which one or more limitations, elements, clauses and descriptive terms from one or more listed claims are introduced into another claim. For example, any claim that is subordinate to another claim can be modified to include one or more limitations found in any other claim that is subordinate to the same basic claim. When element is presented as a list such as with Markush (Markush) group format, each subgroup of these elements is also disclosed, and any one or more elements can be removed from the group. It should be understood that, in general, when the present invention or various aspects of the present invention are referred to as including specific elements and / or features, some embodiments of the present invention or various aspects of the present invention are composed of such elements and / or features or are substantially composed of such elements and / or features. For simplicity, those embodiments are not specifically described herein.

[0327] As used herein in the specification and claims, the phrase "and / or" should be understood to mean "either or both" of the elements so combined, i.e., elements that are present in combination in some cases and separately in other cases. Multiple elements listed with "and / or" should be interpreted in the same manner, i.e., "one or more" of the elements are so connected. In addition to the elements expressly identified with the "and / or" clause, other elements may optionally be present, whether related or unrelated to those elements expressly identified. 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 to only A (optionally including elements other than B) in one embodiment; to only B (optionally including elements other than A) in another embodiment; to both A and B (optionally including other elements) in yet another embodiment; and so on.

[0328] As used herein in the specification and claims, “or” should be understood to have the same meaning as “and / or” as defined above. For example, when used in the context of listing items, “or” or “and / or” shall be interpreted as including (a) one or more of the listed items, (b) one or more of the listed items exclusively, (c) one or more of the listed items in any combination, whether conjoined with a “and” or placed with each other term, and (d) optionally, additional unlisted items. Only terms that are clearly stated to the contrary, such as “only one of’ or “exactly one of,” or when used in the claims, “consisting of’ shall indicate that the interpretation in (b) is not intended. Generally, as used herein, the term “or” as used herein, unless stated to the contrary, should be understood to mean either term or the other term but not both (i.e., it is an inclusive or). When used in a phrase “consisting essentially of’ in a claim, the phrase shall bear its ordinary meaning as used in the patent law.

[0329] As used herein in the specification and claims, the phrase “at least one,” in reference to a list of one or more elements should be understood to mean at least one of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that the

[0330] It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or operation, the order of the steps or operations of the method is not necessarily limited to the order in which the steps or operations are recited.

[0331] In the claims and the foregoing description, all transitional phrases such as "comprising," "including," "with," "having," "containing," "involving," "having," "consisting of," and the like should be understood to be open-ended, i.e., meaning including, but not limited to, including. Only the transitional phrases "consisting of" and "consisting essentially of" should be closed or semi-closed transitional phrases, respectively, as described in Section 2111.03 of the United States Patent Office Manual of Patent Examining Procedures. It should be understood that, in alternative embodiments, embodiments described in this document using open transitional phrases (e.g., "comprising") are also contemplated as "consisting of" and "consisting essentially of" the features described by the open transitional phrases. For example, if the application describes a "composition comprising A and B," the application also contemplates the alternative embodiments "composition consisting of A and B" and "composition consisting essentially of A and B."

[0332] When ranges are given, the endpoints are included. Furthermore, unless otherwise indicated or otherwise apparent from the context and understanding of one of ordinary skill in the art, values ​​expressed as ranges may assume any specific value or sub-range within the range specified in various embodiments of the present invention, to the tenth of the unit of the lower limit of the range, unless the context clearly indicates otherwise.

[0333] This application cites various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any incorporated reference and this specification, the present specification shall prevail. In addition, any specific embodiment of the present invention that is within the prior art may be explicitly excluded from any one or more claims. Because such embodiments are considered to be known to those of ordinary skill in the art, they may be excluded even if the exclusion is not explicitly stated herein. Any specific embodiment of the present invention may be excluded from any claim for any reason, regardless of whether it is related to existing prior art.

[0334] 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 intended to be limited to the above description, but rather to that set forth in the appended claims. Those skilled in the art will recognize that various changes and modifications may be made to this description without departing from the spirit or scope of the invention as defined in the following claims.

[0335] The recitation of a list of chemical groups in any definition of a variable herein includes the definition of that variable as any single group or combination of listed groups. The recitation of embodiments of a variable herein includes embodiments as any single embodiment or in combination with any other embodiment or portions thereof. The recitation of embodiments herein includes embodiments as any single embodiment or in combination with any other embodiment or portions thereof.

Claims

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

2. The isolated antibody of claim 1, wherein the antibody further comprises LC CDR1, LC CDR2, and LC CDR3 of the light chain variable region shown in SEQ ID NO: 8, 56, 70, or 84.

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

79.

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

82.

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

82.

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

84.

7. The antibody of any one of claims 1-5, wherein the antibody comprises 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 1-5 or 7, wherein the antibody comprises 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 of any one of claims 1-9, wherein the antibody is a human antibody.

11. The antibody of any one of claims 1-10, wherein the antibody comprises a heavy chain constant region.

12. The antibody of any one of claims 1-10, wherein the antibody comprises 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 1-13, wherein the antibody is an IgG1 antibody.

15. The antibody of any one of claims 1-14, wherein the antibody comprises a light chain constant region.

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

17. The antibody of any one of claims 14-16, wherein the antibody comprises the heavy chain shown in SEQ ID NO: 11, 57, 71 or 85.

18. The antibody of claim 16 or 17, wherein the antibody comprises the light chain shown in SEQ ID NO: 12, 58, 72 or 86.

19. The antibody of any one of claims 1-18, wherein the antibody comprises: (i) the heavy chain shown in SEQ ID NO: 11 and the light chain shown in SEQ ID NO: 12; (ii) the heavy chain shown in SEQ ID NO: 57 and the light chain shown in SEQ ID NO: 58; (iii) the heavy chain shown in SEQ ID NO:71 and the light chain shown in SEQ ID NO:72; or (iv) the heavy chain shown in SEQ ID NO: 85 and the light chain shown in SEQ ID NO:

86.

20. The antibody of any one of claims 1-19, wherein the antibody further comprises a heterologous moiety.

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

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

23. The antibody of any one of claims 1-19, wherein the antibody is a multispecific antibody that specifically binds CD22 and one or more additional target antigens.

24. The antibody of claim 23, wherein the antibody is a bispecific antibody that specifically binds to CD22 and an additional target antigen.

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

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

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

28. A method for expressing an antibody as described in any one of claims 1-19, 23 or 24 or a fusion protein as described in claim 22, the method comprising culturing the recombinant cell or multiple such cells under conditions suitable for expression of the antibody or fusion protein from the expression vector by the recombinant cell or multiple such cells.

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

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

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

32. A method for treating a B cell disorder, the method 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 as described in any one of claims 1-19, 23 or 24, (ii) a fusion protein as described in claim 22, (iii) an isolated nucleic acid as described in claim 25, (iv) an expression vector as described in claim 26; (v) a recombinant cell as described in claim 27; (vi) an antibody or fusion protein as described in claim 30; or (vii) a pharmaceutical composition as described in claim 31.

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

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

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

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

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

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

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

41. An antibody that specifically binds to human CD22, the antibody comprising HC CDR1, HC CDR2, HC CDR3, LC CDR1, LC CDR2, and LC CDR3, in: (i) (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 1, (b) HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 2; (c) HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: NO:3 has an amino acid sequence that is 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% identical, (d) LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO:4, (e) LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: NO:5 having an amino acid sequence that is 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% identical, and (f) the LC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO:6; (ii) (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 49, (b) HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 50, (c) HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: NO:51 has an amino acid sequence that is 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% identical, (d) LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO:52, (e) LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:53, NO:53 having an amino acid sequence that is 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% identical, and (f) the LC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO:54; (iii) (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 63, (b) HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 64, (c) HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: NO:65 has an amino acid sequence that is 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% identical to SEQ ID NO:66, (d) LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO:67, (e) LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:68, NO:67 has an amino acid sequence that is 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% identical, and (f) the LC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO:68; or (iv) (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 63, (b) HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 78, (c) HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: NO:79 has an amino acid sequence that is 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% identical, (d) LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO:80, (e) LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:81, NO:81 has an amino acid sequence that is 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% identical, and (f) LC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO:

82.

42. The antibody of claim 41, wherein (i) the VH comprises: (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 1; (b) the HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 2; or (c) the HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 3; and The VL contains: (d) the LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO:4; (e) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:5; or (f) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 6; (ii) the VH comprises: (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 49; (b) the HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:50; or (c) the HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 51; and The VL contains: (d) the LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO:52; (e) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 53; or (f) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:54; (iii) the VH comprises: (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 63; (b) the HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 64; or (c) the HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 65; and The VL contains: (d) the LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 66; (e) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 67; or (f) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 68; or (iv) the VH comprises: (a) HC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 63; (b) the HC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 78; or (c) the HC CDR3 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 79; and The VL contains: (d) the LC CDR1 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 80; (e) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO: 81; or (f) the LC CDR2 comprises an amino acid sequence that is 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% identical to SEQ ID NO:

82.

43. The antibody of claim 41 or 42, wherein: (a) The V H comprising at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c), or (iv)(a)-(c); (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) The V H comprises at least two CDRs selected from (i)(a)-(c), (ii)(a)-(c), (iii)(a)-(c) or (iv)(a)-(c), and the V L 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 41-43 for binding to human CD22.

45. The antibody of any one of claims 41-44, wherein the antibody is a human antibody.

46. ​​The antibody of any one of claims 41-45, wherein the antibody comprises a heavy chain constant region.

47. The antibody of any one of claims 41-46, wherein the antibody comprises a human heavy chain constant region.

48. The antibody of any one of claims 41-47, 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 41-48, wherein the heavy chain constant region is IgGl.

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

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 41-51.

53. The antibody of any one of claims 41-52, wherein the antibody is a multispecific antibody that specifically binds CD22 and one or more additional target antigens.

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

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

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

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

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

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

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

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

62. A method for treating a B cell disorder, the method 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 as described in any one of claims 41-49, 53, 54 or 90, (ii) a fusion protein as described in claim 52; (iii) an isolated nucleic acid as described in claim 55, (iv) an expression vector as described in claim 56; (v) a recombinant cell as described in claim 57; (vi) an isolated antibody or fusion protein as described in claim 60; or (vii) a composition as described in claim 61.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

78. An immune cell expressing the CAR of any one of claims 71-75, or comprising the isolated nucleic acid of claim 76 or the expression vector of claim 77.

79. The immune cell of claim 78, wherein the immune cell is a T cell, a NK cell, or a NKT cell.

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

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

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

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

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

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

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

88. The method of any one of claims 81-87, wherein the immune cell or the composition is administered intravenously.

89. The method of any one of claims 81-87, wherein the immune cell or the composition is administered subcutaneously.

90. An antibody comprising: (i) 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 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.

91. An antibody comprising a HC CDR3 comprising the amino acid sequence of ARELTGDAFDX7 (SEQ ID NO: 35), wherein X7 is I or L.

92. The antibody of claim 91, wherein the antibody further comprises: 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; and / or 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.

93. The antibody of claim 91 or 92, wherein the antibody further comprises: 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 a LC CDR3 comprising HQSSX 10 LC CDR3 of the amino acid sequence of EPYT (SEQ ID NO: 38), wherein X 10 It is T, R or S.

94. An antibody comprising: 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 a LC CDR3 comprising the amino acid sequence of HQSSX 10 LC CDR3 of the amino acid sequence of EPYT (SEQ ID NO: 38), wherein X 10 It is T, R or S.

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