WO2019084053A1

WO2019084053A1 - Compositions and methods for the depletion of cd117+ cells

Info

Publication number: WO2019084053A1
Application number: PCT/US2018/057168
Authority: WO
Inventors: Bradley R. PEARSE; Michael Cooke; Anthony Boitano; Rahul Palchaudhuri; Sean MCDONOUGH; Rajiv PANWAR; Jacob Glanville
Original assignee: Magenta Therapeutics, Inc.
Priority date: 2017-10-24
Filing date: 2018-10-23
Publication date: 2019-05-02

Abstract

The invention provides compositions and methods useful for the depletion of CD117+ cells and for the treatment of various hematopoietic diseases, metabolic disorders, cancers, e.g., acute myeloid leukemia (AML) and autoimmune diseases, among others. Described herein are antibodies, and antigen-binding fragments thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ cells in a patient, such as a human. The compositions and methods described herein can be used to treat a disorder directly, for instance, by depleting a population of CD117+ cancer cells or autoimmune cells. The compositions and methods described herein can also be used to prepare a patient for hematopoietic stem cell transplant therapy and to improve the engraftment of hematopoietic stem cell transplants by selectively depleting endogenous hematopoietic stem cells prior to the transplant procedure.

Description

COMPOSITIONS AND METHODS FOR THE DEPLETION OF CD117+ CELLS

Related Applications

This application claims priority to U.S. Provisional Application No. 62/576,572, filed on October 24, 2017; U.S. Provisional Application No. 62/596,569, filed on December 8, 2017; U.S. Provisional Application No. 62/632,967, filed on February 20, 2018; U.S. Provisional Application No. 62/638,048, filed on March 2, 2018, and U.S. Provisional Application No. 62/638,223, filed on March 4, 2018. The contents of each of the priority applications are incorporated by reference herein.

Field of the Invention

The invention relates to anti-CD1 17 antibodies and antigen-binding fragments thereof, as well as methods of treating patients suffering from various pathologies, such as blood diseases, metabolic disorders, cancers, and autoimmune diseases, among others, by administration of an antibody, or antigen-binding fragments thereof, capable of binding an antigen expressed by a hematopoietic cell, such as a hematopoietic stem cell.

Background of the Invention

Despite advances in the medicinal arts, there remains a demand for treating pathologies of the hematopoietic system, such as diseases of a particular blood cell, metabolic disorders, cancers, and autoimmune conditions, among others. While hematopoietic stem cells have significant therapeutic potential, a limitation that has hindered their use in the clinic has been the difficulty associated with ensuring engraftment of hematopoietic stem cell transplants in a host.

There is currently a need for compositions that target specific endogenous stem cells that can be used as conditioning agents to promote the engraftment of exogenous hematopoietic stem cell grafts such that the multi-potency and hematopoietic functionality of these cells is preserved in the patient following transplantation.

CD1 17 (also referred to as c-kit or Stem Cell Factor Receptor (SCRF)) is a single transmembrane, receptor tyrosine kinase that binds the ligand Stem Cell Factor (SCF) . SCF induces homodimerization of cKIT which activates its tyrosine kinase activity and signals through both the PI3-AKT and MAPK pathways (Kindblom et al., Am J. Path. 1998 152(5):1259).

CD1 17 was initially discovered as an oncogene and has been studied in the field of oncology (see, for example, Stankov et al. (2014) Curr Pharm Des. 20(17):2849-80).

CD1 17 is highly expressed on hematopoietic stem cells (HSCs). This expression pattern makes CD1 17 a potential target for conditioning across a broad range of diseases. There remains, however, a need for anti-CD1 17 based therapy that is effective for conditioning a patient for transplantation, such as a bone marrow transplantation. Summary of the Invention

Described herein are antibodies, and antigen binding portions thereof, that specifically bind human CD1 17 (also known as c-kit), as well as compositions and methods of using said antibodies.

In one embodiment, the present invention provides compositions and methods for the direct treatment of various disorders of the hematopoietic system, metabolic disorders, cancers, and autoimmune diseases, among others. The invention additionally features methods for conditioning a patient, such as a human patient, prior to receiving hematopoietic stem cell transplant therapy so as to promote the engraftment of hematopoietic stem cell grafts. The patient may be one that is suffering from one or more blood disorders, such as a hemoglobinopathy or other hematopoietic pathology, and is thus in need of hematopoietic stem cell transplantation. As described herein, hematopoietic stem cells are capable of differentiating into a multitude of cell types in the hematopoietic lineage, and can be administered to a patient in order to populate or re- populate a cell type that is deficient in the patient. The invention features methods of treating a patient with antibodies capable of binding proteins expressed by hematopoietic cells, such as CD1 17 (including, for example, GNNK+ CD1 17), so as to (i) directly treat a disease such as a blood disorder, metabolic disease, cancer, or autoimmune disease, among others described herein, by selectively depleting a population of cells that express CD1 17, such as an aberrant blood cell, cancer cell, or autoimmune cell, and/or (ii) deplete a population of endogenous hematopoietic stem cells within the patient. The former activity enables the direct treatment of a wide range of disorders associated with a cell of the hematopoietic lineage, as CD1 17 may be expressed by a cancerous cell, such as a leukemic cell, an autoimmune lymphocyte, such as a T- cell that expresses a T-cell receptor that cross-reacts with a self antigen, among other cell types. The latter activity, the selective depletion of hematopoietic stem cells, in turn creates a vacancy that can subsequently be filled by transplantation of an exogenous (for instance, an autologous, allogeneic, or syngeneic) hematopoietic stem cell graft. The invention thus provides methods of treating a variety of hematopoietic conditions, such as sickle cell anemia, thalassemia, Fanconi anemia, Wiskott-Aldrich syndrome, adenosine deaminase deficiency-severe combined

immunodeficiency, metachromatic leukodystrophy, Diamond-Blackfan anemia and Schwachman- Diamond syndrome, human immunodeficiency virus infection, and acquired immune deficiency syndrome, as well as cancers and autoimmune diseases, among others.

In one aspect, the invention provides a method of depleting a population of CD1 17+ cells in a human patient by administering an effective amount of an antibody, or antigen-binding fragment thereof, capable of binding CD1 17.

In another aspect, the invention provides a method of depleting a population of CD1 17+ cells in a human patient in need of a hematopoietic stem cell transplant by administering, prior to the patient receiving a transplant including hematopoietic stem cells, an effective amount of an antibody or antigen-binding fragment thereof capable of binding CD1 17. In another aspect, the invention features a method, for example, of treating a human patient in need of a hematopoietic stem cell transplant, including administering to a human patient a transplant including hematopoietic stem cells, wherein the patient has been previously administered an antibody or antigen-binding fragment thereof capable of binding CD1 17 in an amount sufficient to deplete a population of CD1 17+ cells in the patient.

In an additional aspect, the invention features a method, for example, of treating a human patient in need of a hematopoietic stem cell transplant, including: administering to a human patient an antibody or antigen-binding fragment thereof capable of binding CD1 17 in an amount sufficient to deplete a population of CD1 17+ cells in the patient, and subsequently administering to the patient a transplant including hematopoietic stem cells.

In another aspect, the invention features a method of depleting a population of CD1 17+ cells in a human patient by administering an effective amount of an antibody, or an antigen-binding fragment, capable of binding GNNK+ CD1 17.

In an additional, the invention features a method of depleting a population of CD1 17+ cells in a human patient in need of a hematopoietic stem cell transplant by administering, prior to the patient receiving a transplant containing hematopoietic stem cells, an effective amount of an antibody or antigen-binding fragment thereof, capable of binding GNNK+ CD1 17.

In another aspect, the invention features a method, for example, of treating a human patient in need of a hematopoietic stem cell transplant, including administering to a human patient a transplant containing hematopoietic stem cells, wherein the patient has been previously administered an antibody, antigen-binding fragment thereof, capable of binding GNNK+ CD1 17 in an amount sufficient to deplete a population of CD1 17+ cells in the patient.

In an additional aspect, the invention features a method, for example, of treating a human patient in need of a hematopoietic stem cell transplant, including: administering to a human patient an antibody, antigen-binding fragment thereof, capable of binding GNNK+ CD1 17 in an amount sufficient to deplete a population of CD1 17+ cells in the patient, and subsequently administering to the patient a transplant including hematopoietic stem cells.

In some embodiments of any of the above aspects, the antibody, antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody or antigen-binding fragment thereof, a polyclonal antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a bispecific antibody or antigen-binding fragment thereof, a dual-variable immunoglobulin domain, a single-chain Fv molecule (scFv), a diabody, a triabody, a nanobody, an antibody-like protein scaffold, a Fv fragment, a Fab fragment, a F(ab')₂ molecule, and a tandem di-scFv. In some embodiments, the antibody has an isotype selected from the group consisting of IgG, IgA, IgM, IgD, and IgE.

In some embodiments of any of the above aspects, the antibody, or antigen-binding fragment thereof, is internalized by a hematopoietic cell, such as a hematopoietic stem cell, cancer cell, or autoimmune cell following administration to the patient. For instance, the antibody, or antigen-binding fragment thereof, may be internalized by hematopoietic stem cells, cancer cells, or autoimmune cells by receptor-mediated endocytosis (e.g., upon binding to cell-surface CD1 17, such as GNNK+ CD1 17).

In some embodiments of any of the above aspects, the antibody, or antigen-binding fragment thereof, is capable of promoting necrosis of a hematopoietic cell, such as a

hematopoietic stem cell, cancer cell, or autoimmune cell, among others. In some embodiments, the antibody or antigen-binding fragment thereof may promote the death of an endogenous hematopoietic stem cell prior to transplantation therapy, an endogenous cancer cell, or an endogenous autoimmune cell, among others, by recruiting one or more complement proteins, natural killer (NK) cells, macrophages, neutrophils, and/or eosinophils to the cell, such as a hematopoietic stem cell upon administration to the patient.

In some embodiments of any of the above aspects, the transplant containing hematopoietic stem cells is administered to the patient after the concentration of the antibody, antigen-binding fragment thereof, has substantially cleared from the blood of the patient.

In some embodiments of any of the above aspects, the hematopoietic stem cells or progeny thereof maintain hematopoietic stem cell functional potential after two or more days (for example, from about 2 to about 5 days, from about 2 to about 7 days, from about 2 to about 20 days, from about 2 to about 30 days, such as 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 1 1 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days, 21 days, 22 days, 23 days, 24 days, 25 days, 26 days, 27 days, 28 days, 29 days, 30 days, or more) following transplantation of the hematopoietic stem cells into the patient.

In some embodiments of any of the above aspects, the hematopoietic stem cells or progeny thereof are capable of localizing to hematopoietic tissue, such as the bone marrow, and/or reestablishing hematopoiesis following transplantation of the hematopoietic stem cells into the patient.

In some embodiments of any of the above aspects, upon transplantation into the patient, the hematopoietic stem cells give rise to recovery of a population of cells selected from the group consisting of megakaryocytes, thrombocytes, platelets, erythrocytes, mast cells, myeoblasts, basophils, neutrophils, eosinophils, microglia, granulocytes, monocytes, osteoclasts, antigen- presenting cells, macrophages, dendritic cells, natural killer cells, T-lymphocytes, and B- lymphocytes.

In some embodiments of any of the above aspects, the method is used to treat one or more disorders, such as by depleting a population of hematopoietic stem cells in a patient prior to hematopoietic stem cell transplant therapy so as to provide a niche to which the transplanted hematopoietic stem cells may home. Following transplantation, the hematopoietic stem cells may establish productive hematopoiesis, so as to replenish a deficient cell type in the patient or a cell type that is being actively killed or has been killed, for instance, by chemotherapeutic methods.

For instance, the patient may be one that is suffering from a stem cell disorder. In some embodiments, the patient is suffering from a hemoglobinopathy disorder, such as sickle cell anemia, thalassemia, Fanconi anemia, aplastic anemia, and Wiskott-Aldrich syndrome. The patient may be suffering from an immunodeficiency disorder, such as a congenital

immunodeficiency disorder or an acquired immunodeficiency disorder (e.g., human

immunodeficiency virus or acquired immune deficiency syndrome). In some embodiments, the patient is suffering from a metabolic disorder, such as glycogen storage diseases,

mucopolysaccharidoses, Gaucher's Disease, Hurlers Disease, sphingolipidoses, and

metachromatic leukodystrophy. In some embodiments, the patient is suffering from a disorder selected from the group consisting of adenosine deaminase deficiency and severe combined immunodeficiency, hyper immunoglobulin M syndrome, Chediak-Higashi disease, hereditary lymphohistiocytosis, osteopetrosis, osteogenesis imperfecta, storage diseases, thalassemia major, systemic sclerosis, systemic lupus erythematosus, and juvenile rheumatoid arthritis. In some embodiments, the patient is suffering from an autoimmune disease, such as scleroderma, multiple sclerosis, ulcerative colitis, Crohn's disease, ant Type 1 diabetes. In some embodiments, the patient is suffering from cancer or myeloproliferative disease, such as a hematological cancer. In some embodiments, the patient is suffering from acute myeloid leukemia (AML), acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple meloma, diffuse large B- cell lymphoma, or non-Hodgkin's lymphoma. In some embodiments, the patient is suffering from a myelodysplastic disease, such as myelodysplastic syndrome.

In some embodiments of any of the above aspects, the method is used to directly treat a cancer, such as a cancer characterized by CD1 17+ cells (e.g., a leukemia characterized by CD1 17+ cells), by administration of an antibody, or antigen-binding fragment thereof, that depletes a population of CD1 17+ cancer cells in the patient and/or by administration of an antibody, or antigen-binding fragment thereof, so as to deplete a population of endogenous hematopoietic stem cells prior to hematopoietic stem cell transplantation. In the latter case, the transplantation may in turn re-constitute, for example, a population of cells depleted during the process of eradicating cancer cells. The cancer may be a hematological cancer, such as acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymohoid leukemia, multiple meloma, diffuse large B-cell lymphoma, or non-Hodgkin's lymphoma.

In some embodiments of any of the above aspects, the method is used to treat an autoimmune disease, such as by administration of an antibody, or antigen-binding fragment thereof, so as to deplete a population of CD1 17+ autoimmune cells and/or by administration of an antibody, or antigen-binding fragment thereof, so as to deplete a population of endogenous hematopoietic stem cells prior to hematopoietic stem cell transplantation. In the latter case, the transplantation may in turn re-constitute, for example, a population of cells depleted during the process of eradicating autoimmune cells. The autoimmune disease may be, for example, scleroderma, multiple sclerosis (MS), human systemic lupus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), treating psoriasis, Type 1 diabetes mellitus (Type 1 diabetes), acute disseminated encephalomyelitis (ADEM), Addison's disease, alopecia universalis, ankylosing spondylitisis, antiphospholipid antibody syndrome (APS), aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune lymphoproliferative syndrome (ALPS), autoimmune oophoritis, Balo disease, Behcet's disease, bullous pemphigoid, cardiomyopathy, Chagas' disease, chronic fatigue immune dysfunction syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy, Crohn's disease, cicatrical pemphigoid, coeliac sprue-dermatitis herpetiformis, cold agglutinin disease, CREST syndrome, Degos disease, discoid lupus, dysautonomia, endometriosis, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Goodpasture' s syndrome, Grave's disease, Guillain- Barre syndrome (GBS), Hashimoto' s thyroiditis, Hidradenitis suppurativa, idiopathic and/or acute thrombocytopenic purpura, idiopathic pulmonary fibrosis, IgA neuropathy, interstitial cystitis, juvenile arthritis, Kawasaki's disease, lichen planus, Lyme disease, Meniere disease, mixed connective tissue disease (MCTD), myasthenia gravis, neuromyotonia, opsoclonus myoclonus syndrome (OMS), optic neuritis, Ord's thyroiditis, pemphigus vulgaris, pernicious anemia, polychondritis, polymyositis and dermatomyositis, primary biliary cirrhosis, polyarteritis nodosa, polyglandular syndromes, polymyalgia rheumatica, primary agammaglobulinemia, Raynaud phenomenon, Reiter' s syndrome, rheumatic fever, sarcoidosis, scleroderma, Sjogren's syndrome, stiff person syndrome, Takayasu's arteritis, temporal arteritis ( also known as "giant cell arteritis"), ulcerative colitis, uveitis, vasculitis, vitiligo, vulvodynia ("vulvar vestibulitis"), and Wegener's granulomatosis.

Thus, in some embodiments of any of the above aspects, the invention features a method of treating a hemoglobinopathy disorder, such as sickle cell anemia, thalassemia, Fanconi anemia, aplastic anemia, and Wiskott-Aldrich syndrome. In some embodiments, the invention features a method of treating an immunodeficiency disorder, such as a congenital immunodeficiency disorder or an acquired immunodeficiency disorder (e.g., human immunodeficiency virus or acquired immune deficiency syndrome). In some embodiments, the invention features a method of treating a metabolic disorder, such as glycogen storage diseases, mucopolysaccharidoses, Gaucher's

Disease, Hurlers Disease, sphingolipidoses, and metachromatic leukodystrophy. In some embodiments, the invention features a method of treating a disorder selected from the group consisting of adenosine deaminase deficiency and severe combined immunodeficiency, hyper immunoglobulin M syndrome, Chediak-Higashi disease, hereditary lymphohistiocytosis, osteopetrosis, osteogenesis imperfecta, storage diseases, thalassemia major, systemic sclerosis, systemic lupus erythematosus, and juvenile rheumatoid arthritis In some embodiments, the invention features a method of treating an autoimmune disease, such as scleroderma, multiple sclerosis, ulcerative colitis, Crohn's disease, ant Type 1 diabetes. In some embodiments, the invention features a method of treating a cancer or myeloproliferative disease, such as a hematological cancer. In some embodiments, the invention features a method of treating acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymohoid leukemia, multiple meloma, diffuse large B-cell lymphoma, or non-Hodgkin's lymphoma. In some embodiments, the patient is suffering from a myelodyplastic disease, such as myelodysplastic syndrome. In these embodiments, the method may include the steps of administering an antibody, or antigen-binding fragment thereof, that binds CD1 17 (e.g., GNNK+ CD1 17) and/or a

hematopoietic stem cell transplant according to the method of any of the above-described aspects and embodiments of the invention.

Similarly, in some embodiments of any of the above aspects, the invention provides a method of treating cancer directly, such as a cancer characterized by CD1 17+ cells (e.g., a leukemia characterized by CD1 17+ cells). In these embodiments, the method includes

administering an antibody, or antigen-binding fragment thereof, that binds CD1 17 (e.g., GNNK+ CD1 17). The cancer may be a hematological cancer, such as acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymohoid leukemia, multiple meloma, diffuse large B-cell lymphoma, or non-Hodgkin's lymphoma.

Additionally, in some embodiments of any of the above aspects, the invention provides a method of treating an autoimmune disease, such as multiple sclerosis (MS), human systemic lupus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD), treating psoriasis, Type 1 diabetes mellitus (Type 1 diabetes) acute disseminated encephalomyelitis (ADEM), Addison's disease, alopecia universalis, ankylosing spondylitisis, antiphospholipid antibody syndrome (APS), aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune lymphoproliferative syndrome (ALPS), autoimmune oophoritis, Balo disease, Behcet's disease, bullous pemphigoid, cardiomyopathy, Chagas' disease, chronic fatigue immune dysfunction syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy, Crohn's disease, cicatrical pemphigoid, coeliac sprue-dermatitis herpetiformis, cold agglutinin disease, CREST syndrome, Degos disease, discoid lupus, dysautonomia, endometriosis, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Goodpasture' s syndrome, Grave's disease, Guillain-Barre syndrome (GBS), Hashimoto' s thyroiditis, Hidradenitis suppurativa, idiopathic and/or acute thrombocytopenic purpura, idiopathic pulmonary fibrosis, IgA neuropathy, interstitial cystitis, juvenile arthritis, Kawasaki's disease, lichen planus, Lyme disease, Meniere disease, mixed connective tissue disease (MCTD), myasthenia gravis, neuromyotonia, opsoclonus myoclonus syndrome (OMS), optic neuritis, Ord's thyroiditis, pemphigus vulgaris, pernicious anemia, polychondritis, polymyositis and dermatomyositis, primary biliary cirrhosis, polyarteritis nodosa, polyglandular syndromes, polymyalgia rheumatica, primary agammaglobulinemia, Raynaud phenomenon, Reiter' s syndrome, rheumatic fever, sarcoidosis, scleroderma, Sjogren's syndrome, stiff person syndrome, Takayasu's arteritis, temporal arteritis ( also known as "giant cell arteritis"), ulcerative colitis, uveitis, vasculitis, vitiligo, vulvodynia ("vulvar vestibulitis"), and

Wegener' s granulomatosis. In these embodiments, the method includes administering an antibody, or antigen-binding fragment thereof, that binds CD1 17 (e.g., GNNK+ CD1 17). In some embodiments of these aspects, the antibody or antigen-binding fragment thereof binds CD1 17 with a K_d of less than 1 μΜ, less than 750 nM, less than 500 nM, less than 250 nM, less than 200 nM, less than 150 nM, less than 100 nM, less than 75 nM, less than 50 nM, less than 10 nM, less than 1 nM, less than 0.1 nM, less than 10 pM, less than 1 pM, or less than 0.1 pM. In some embodiments, the K_d is from about 0.1 pM to about 1 μΜ.

In some embodiments of these aspects, the antibody or antigen-binding fragment thereof binds CD1 17 with a k_on of from about 9 x 10^"2 M^"1 s^"1 to about 1 x 10² M^"1 s^"1.

In some embodiments of these aspects, the antibody or antigen-binding fragment thereof competitively inhibits the binding of CD1 17 to a second antibody or antigen binding fragment thereof, or binds the same epitope as a second antibody, wherein the second antibody or antigen- binding fragment thereof has the following complementarity determining regions (CDRs):

a CDR-H1 having the amino acid sequence SYWIG (SEQ ID NO: 1 );

a CDR-H2 having the amino acid sequence IIYPGDSDTRYSPSFQG (SEQ ID NO: 2);

a CDR-H3 having the amino acid sequence HGRGYNGYEGAFDI (SEQ ID NO: 3);

a CDR-L1 having the amino acid sequence RASQGISSALA (SEQ ID NO: 4);

a CDR-L2 having the amino acid sequence DASSLES (SEQ ID NO: 5); and

a CDR-L3 having the amino acid sequence CQQFNSYPLT (SEQ ID NO: 6).

The disclosure further provides isolated anti-CD1 17 antibodies, or antigen-binding fragments thereof, disclosed herein comprising heavy and light chain CDRs and variable regions described in Table 1 , Table 5, or Table 7.

In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 8. In one

embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 9. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 10. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 1 1 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID

NO: 12. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 13. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 14. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 15. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 16. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 17. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 18. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 19. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 20. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 21 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 22. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 23. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 24, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 25. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 26, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 27. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 28, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 29. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 30, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 31 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 32, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 33. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

34, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 35. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 36, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 37. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 38, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 39. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 40, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 41 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 32, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 42. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 43, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 44. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

45, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 46. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 47, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 48. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 49, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 50. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 51 , and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 52. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 53, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 54. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 55, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 56. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

57, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 58. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 59, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 60. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 61 , and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 50. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 62, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 63. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 64, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 65. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 66, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 67. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

68, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 69. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 70, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 71 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 72, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 73. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 74, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 75. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 76, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 77. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 78, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 79. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

80, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 81 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 82, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 84, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 85. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 86, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 87. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 88. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 89. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 90. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 91 . In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 92. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 93. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 94. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO:95. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 96. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 97. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 97. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 143, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 144. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 151 , and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 152. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 143, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 156. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 159, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 156. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 160, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 152. In one embodiment, the anti- CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 98, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 99. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 99. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 100. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 98, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 101 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 98, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 102.

In some embodiments of these aspects, the antibody, or antigen-binding fragment thereof, is selected from the group consisting of a monoclonal antibody or antigen-binding fragment thereof, a polyclonal antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a bispecific antibody or antigen-binding fragment thereof, a dual- variable immunoglobulin domain, a single-chain Fv molecule (scFv), a diabody, a triabody, a nanobody, an antibody-like protein scaffold, a Fv fragment, a Fab fragment, a F(ab')₂ molecule, and a tandem di-scFV. In one embodiment, the antibody is an intact antibody.

In some embodiments of this aspect, the antibody, or antigen-binding fragment thereof, is internalized by a CD1 17+ cell. In some embodiments of this aspect, the antibody, or antigen-binding fragment thereof, binds CD1 17 with a K_d of less than 1 μΜ, less than 750 nM, less than 500 nM, less than 250 nM, less than 200 nM, less than 150 nM, less than 100 nM, less than 75 nM, less than 50 nM, less than 10 nM, less than 1 nM, less than 0.1 nM, less than 10 pM, less than 1 pM, or less than 0.1 pM measured by bio-layer interferometry (BLI). In some embodiments, the K_d is from about 0.1 pM to about 1 μΜ.

In some embodiments of this aspect, the antibody, or antigen-binding fragment thereof, binds CD1 17 with a k_on of from about 9 x 10^"2 M^"1 s^"1 to about 1 x 10² M^"1 s^"1 measured by a bio- layer interferometry (BLI) assay.

In certain embodiments, an anti-CD1 17 antibody, or antigen binding fragment thereof, has a certain dissociation rate which is particularly advantageous. For example, an anti-CD1 17 antibody has, in certain embodiments, an off rate constant (Kdis) for human CD1 17 of 1 x 10^~2 to 1 x 10^"7, 1 x 10^"3 to 1 x 10^"7, 1 x 10^"4 to 1 x 10^"7, 1 x 10^"5 to 1 x 10^"7 , or 1 x 10^"6 to 1 x 10^"7 s^"1 , measured by bio-layer interferometry (BLI).

In some embodiments of this aspect, the antibody, or antigen-binding fragment thereof, competitively inhibits the binding of CD1 17 to a second antibody or antigen binding fragment thereof, wherein the second antibody or antigen-binding fragment thereof has the following CDRs: a. a CDR-H1 having the amino acid sequence SYWIG (SEQ ID NO: 1 );

b. a CDR-H2 having the amino acid sequence IIYPGDSDTRYSPSFQG (SEQ ID NO: 2); c. a CDR-H3 having the amino acid sequence HGRGYNGYEGAFDI (SEQ ID NO: 3);

d. a CDR-L1 having the amino acid sequence RASQGISSALA (SEQ ID NO: 4);

e. a CDR-L2 having the amino acid sequence DASSLES (SEQ ID NO: 5); and

f. a CDR-L3 having the amino acid sequence CQQFNSYPLT (SEQ ID NO: 6).

In some embodiments of this aspect, the antibody or antigen-binding fragment thereof is selected from the group consisting of a monoclonal antibody or antigen-binding fragment thereof, a polyclonal antibody or antigen-binding fragment thereof, a humanized antibody or antigen-binding fragment thereof, a bispecific antibody or antigen-binding fragment thereof, a dual-variable immunoglobulin domain, a single-chain Fv molecule (scFv), a diabody, a triabody, a nanobody, an antibody-like protein scaffold, a Fv fragment, a Fab fragment, a F(ab')₂ molecule, and a tandem di- scFv. In some embodiments, the antibody has an isotype selected from the group consisting of IgG, IgA, IgM, IgD, and IgE.

In certain embodiments, the foregoing methods and compositions include an isolated anti-

CD1 17 antibody or antigen-binding fragment thereof comprising the CDRs set forth in the heavy and light chain amino acid sequences set forth in Table 1 , Table 5, or Table 7. In certain embodiments, the foregoing methods and compositions include an anti-CD1 17 antibody or antigen-binding fragment thereof comprising the variable regions set forth in the heavy and light chain amino acid sequences set forth in Table 1 . In certain embodiments, the foregoing methods and compositions include an lgG1 anti-CD1 17 antibody or antigen-binding fragment thereof comprises the variable regions set forth in the heavy and light chain amino acid sequences set forth in Table 1 , Table 5, or Table 7.

In another aspect, the invention features a method treating acute myeloid leukemia (AML) in a human patient, the method comprising administering an effective amount of an anti-CD1 17 antibody to the human patient such that AML is treated. In certain embodiments, the anti-CD1 17 antibody comprises the CDR sequences set forth in the heavy and light chain amino acid sequences of Table 1 . In yet other embodiments, the anti-CD1 17 antibody is an intact antibody. In another embodiment, the antibody is an lgG1 or an lgG4.

In one aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen- binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 145, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 147; and comprising a light chain variable region comprising a CDR1 comprising the amino acid sequence as set forth in SEQ ID NO: 148, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:149, and a CDR3 comprising the amino acid sequence as set forth in SEQ ID NO: 150.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 143, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 144.

In a further aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:153, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 154, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 151 , and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 152.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:146, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 147; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 157, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 143, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 156.

In yet another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:159, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 157, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 158, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 156.

In a further aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 154, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 160, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 152.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 99.

In a further aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 99.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 100.

In an additional aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 101 .

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 186, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 187; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 188, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 189.

In yet another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 102.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 163, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 164, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:168, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 166.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 95. In yet another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 163, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 167, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:165, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 166.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 93.

In a further aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 163, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 164, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:165, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 166.

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 91 .

In another aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain comprising the heavy chain CDR sets (CDR1 , CDR2, and CDR3) forth in the heavy chain amino acid sequences described in Table 1 , Table 6 or Table 8, and a light chain comprising the heavy chain CDR sets (CDR1 , CDR2, and CDR3) forth in the light chain amino acid sequences described in Table 1 , Table 5 or Table 7.

In a further aspect, the present invention provides an isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region as forth in Table 1 , Table 5 or Table 7, and a light chain comprising the light chain variable region as forth in Table 1 , Table 5 or Table 7.

In another aspect, the present invention provides an anti-CD1 17 antibody, or antigen binding fragment thereof, as described herein, wherein the antibody, or antigen binding fragment, has a dissociation rate (k_dis) of 1 x 10^"2 to 1 x 10^"3, 1 x 10^"3 to 1 x 10^"4, 1 x 10^"5 to 1 x 10^"6, 1 x 10^"6 to

1 x 10^"7 or 1 x 10^"7 to 1 x 10^"8as measured by bio-layer interferometry (BLI). In some

embodiments, the anti-CD1 17 antibody, or antigen binding fragment thereof, as described herein, binds CD1 17 with a K_D of about 100 nM or less, about 90nM or less, about 80 nM or less, about 70 nM or less, about 60 nM or less, about 50 nM or less, about 40 nM or less, about 30 nM or less, about 20 nM or less, about 10 nM or less, about 8 nM or less, about 6 nM or less, about 4 nM or less, about 2 nM or less, about 1 nM or less as determined by a Bio-Layer Interferometry (BLI) assay. In another embodiment, the anti-CD1 17 antibody, or antigen binding fragment thereof, as described herein, is human. In another embodiment, the anti-CD1 17 antibody, or antigen binding fragment thereof, is an intact antibody. In yet another embodiment, the anti-CD1 17 antibody or antigen-binding fragment thereof is an IgG. In other embodiments, the anti-CD1 17 antibody or antigen-binding fragment thereof, is an lgG1 or an lgG4. In yet other embodiments, the anti- CD1 17 antibody or antigen-binding fragment thereof, is a monoclonal antibody. In yet another embodiment, the anti-CD1 17 antibody or antigen-binding fragment thereof, comprises a heavy chain constant region having an amino acid sequence as set forth as SEQ ID NO: 169 and/or a light chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 183.

In other embodiments, the anti-CD1 17 antibody or antigen-binding fragment thereof, comprises an Fc region comprising at least one amino acid substitution selected from the group consisting of D265C, H435A, L234AA, and L235A (numbering according to the EU index). In certain embodiments, the Fc region comprises amino acid substitutions D265C, L234A, and L235A (numbering according to the EU index).

In another aspect, the present invention provides an intact anti-CD1 17 human antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 184, and a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 175, SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178.

In another aspect, the present invention provides an intact anti-CD1 17 human antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 185, and a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 179, SEQ ID NO: 180, SEQ ID NO: 181 , and SEQ ID NO: 182.

In another aspect, the present invention provides a method of depleting a population of CD1 17+ cells in a human patient comprising administering an antibody, as described herein, to the human patient. In certain embodiments, the human patient is in need of a hematopoietic stem cell transplant.

In another aspect, the present invention provides a method of treating a human subject having a hematological cancer comprising administering an anti-CD1 17, or antigen binding fragment thereof, as described herein, to the human subject having the hematological cancer. In certain embodiments, the hematological cancer is leukemia.

In another aspect, the present invention provides a pharmaceutical composition comprising an antibody, or antigen-binding portion thereof, as described herein, and a pharmaceutically acceptable carrier. Brief Description of the Figures

Fig. 1 demonstrates the measurement of binding by Bio-Layer Interferometry (BLI) of the indicated purified IgG (sensor-associated) to purified human CD1 17 ectodomain (R&D Systems #332-SR) at concentrations of 33.3 nM (top traces) and 1 1 nM (bottom traces) as a function of time. The purified IgGs correspond to Ab1 (i.e., 001 ), Ab2 (i.e., 002), Ab3 (i.e., 003), Ab4 (i.e., 004), Ab5 (i.e., 005), Ab6 (i.e., 006), Ab7 (i.e., 007), Ab8 (i.e., 008), Ab9 (i.e., 009), Ab10 (i.e., 010), Ab1 1 (i.e., 01 1 ), Ab12 (i.e., 012), Ab13 (i.e., 013), Ab14 (i.e., 014), Ab15 (i.e., 015), and Ab16 (i.e., 016).

Fig. 2 graphically depicts the results of a non-human primate pharmacokinetic assay expressed as the concentration (ng/mL) of an isotype control antibody (i.e., "wild type antibody") in comparison to an CK6 variant antibody with a shorter half life as a function time (i.e., hours post- administration; x-axis).

Figs. 3A, 3B, 3C and 3D describe measurement of anti-CD1 17 antibody binding by Bio- Layer Interferometry (BLI) of the indicated purified IgG (sensor-associated) to purified human CD1 17 ectodomain (R&D Systems #332-SR) at concentrations of 33.3 nM (top trace) and 1 1 nM (bottom trace) as a function of time for the (A) HC-1 /LC-1 (Ab1 ) antibody, (B) the HC-77/LC-77 (Ab 77) antibody, (C) the HC-79/LC-79 (Ab79) antibody, and (D) the HC-81/LC-81 (Ab81 ) antibody.

Figs. 4A and 4B demonstrate the measurement of binding by Bio-Layer Interferometry (BLI) of the indicated purified IgG (sensor-associated) to purified human CD1 17 ectodomain (R&D Systems #332-SR) at concentrations of 33.3 nM (top traces) and 1 1 nM (bottom traces) as a function of time for the (A) HC-85/LC-85 antibody and the (B) HC-1/LC-1 antibody.

Figs. 5A, 5B, 5C, and 5D provide the variable heavy (VH) and variable light (VL) chain region of the amino acid sequences of CK6, Ab85 and Ab249. (A) Depicts the alignment of the variable heavy (VH) chain regions of CK6 (SEQ ID NO: 161 ) and Ab85 (SEQ ID NO: 143). (B) Depicts the alignment of the variable light (VL) chain regions of CK6 (SEQ ID NO: 162) and Ab85 (SEQ ID NO: 144). (C) Depicts the alignment of the variable heavy (VH) chain regions of CK6 (SEQ ID NO: 161 ) and Ab249 (SEQ ID NO: 98). (D) Depicts the alignment of the variable light (VL) chain regions of CK6 (SEQ ID NO: 162) and Ab249 (SEQ ID NO: 102).

Figs. 6A, 6B and 6C depict the binding by bio-layer interferometry (BLI) of the indicated purified IgG (sensor-associated) to 1 1 nm (bottom trace) and 33 nM (top trace) purified human CD1 17 ectodomain as a function of time for the (A) CK6 antibody, (B) the HC-85/LC-85 (Ab85) antibody and the (C) HC-249/LC-249 (Ab 249) antibody.

Figs. 7A and 7B illustrate the fraction of acidic variants present in the indicated antibody under the indicated incubation conditions (x-axis) for (A) Day 7 (25 ^eC and 50 ^eC) and (B) Day 15 (25 ^eC and 50 ^eC) compared to T₀ as determined by capillary electrophoresis.

Figs. 8A, 8B, 8C, 8D and 8E depict chromatograms demonstrating the elution profile of (A) the CK6 antibody, (B) the HC-77 / LC-77 (Ab77) antibody, (C) the HC-79 / LC-79 (Ab79) antibody,

(D) the HC-81 / LC-81 (Ab81 ) antibody, and (E) the HC-85 / LC-85 (Ab85) antibody, under the indication incubation conditions (see legend) after analysis by hydrophobic interaction chromatography (HIC).

Fig. 9 demonstrates the measurement of binding by Bio-Layer Interferometry (BLI) of the indicated purified IgG (sensor-associated) to 100 nM purified human CD1 17 ectodomain (R&D Systems #332-SR) as a function of time. The purified IgGs correspond to Ab17 (i.e., 017), Ab18 (i.e., 018), Ab19 (i.e., 019), Ab20 (i.e., 020), Ab21 (i.e., 021 ), Ab22 (i.e., 022), Ab23 (i.e., 023), Ab24 (i.e., 024), Ab25 (i.e., 025), Ab27 (i.e., 027), and Ab28 (i.e., 028).

Fig. 10 demonstrates the measurement of binding by Bio-Layer Interferometry (BLI) of the indicated purified IgG (sensor-associated) to 100 nM purified rhesus CD1 17 ectodomain as a function of time. The purified IgGs correspond to Ab17 (i.e., 017), Ab18 (i.e., 018), Ab19 (i.e., 019), Ab20 (i.e., 020), Ab21 (i.e., 021 ), Ab22 (i.e., 022), Ab23 (i.e., 023), Ab24 (i.e., 024), Ab25 (i.e., 025), Ab27 (i.e., 027), and Ab28 (i.e., 028).

Detailed Description

Described herein are isolated anti-CD1 17 human antibodies that bind to human CD1 17. The antibodies provided herein have many characteristics making them advantageous for therapy, including methods of conditioning human patients for stem cell transplantation. For example, antibodies disclosed herein, in certain embodiments, have high affinity and a law off rate for human CD1 17, as well as the ability to internalize in cells expressing CD1 17. Further, certain of the antibodies presented herein have improved biophysical stability.

The invention provides anti-CD1 17 antibodies, specifically isolated human anti-CD1 17 antibodies that bind to the ectodomain of human CD1 17. The binding regions of the isolated anti- CD1 17 antibodies identified herein are described below and in Table 1 , Table 5, and Table 7.

The anti-CD1 17 antibodies described herein can be used in methods of treating a variety of disorders, such as diseases of a cell type in the hematopoietic lineage, cancers, autoimmune diseases, metabolic disorders, and stem cell disorders, among others. The compositions and methods described herein may (i) directly deplete a population of cells that give rise to a pathology, such as a population of cancer cells (e.g., leukemia cells) and autoimmune cells (e.g., autoreactive T-cells), and/or (ii) deplete a population of endogenous hematopoietic stem cells so as to promote the engraftment of transplanted hematopoietic stem cells by providing a niche to which the transplanted cells may home. The foregoing activities can be achieved by

administration of an antibody, or antigen-binding fragment thereof, capable of binding an antigen expressed by an endogenous disease-causing cell or a hematopoietic stem cell. In the case of direct treatment of a disease, this administration can cause a reduction in the quantity of the cells that give rise to the pathology of interest. In the case of preparing a patient for hematopoietic stem cell transplant therapy, this administration can cause the selective depletion of a population of endogenous hematopoietic stem cells, thereby creating a vacancy in the hematopoietic tissue, such as the bone marrow, that can subsequently be filled by transplanted, exogenous hematopoietic stem cells. The invention is based in part on the discovery that antibodies, or antigen-binding fragments thereof, capable of binding CD1 17 (such as GNNK+ D1 17) can be administered to a patient to affect both of the above activities. Antibodies, or antigen-binding fragments thereof, that bind CD1 17 can be administered to a patient suffering from a cancer or autoimmune disease to directly deplete a population of cancerous cells or autoimmune cells, and can also be administered to a patient in need of hematopoietic stem cell transplant therapy in order to promote the survival and engraftment potential of transplanted hematopoietic stem cells.

Engraftment of hematopoietic stem cell transplants due to the administration of anti-CD1 17 antibodies, or antigen-binding fragments thereof, can manifest in a variety of empirical measurements. For instance, engraftment of transplanted hematopoietic stem cells can be evaluated by assessing the quantity of competitive repopulating units (CRU) present within the bone marrow of a patient following administration of an antibody or antigen-binding fragment thereof capable of binding CD1 17 and subsequent administration of a hematopoietic stem cell transplant. Additionally, one can observe engraftment of a hematopoietic stem cell transplant by incorporating a reporter gene, such as an enzyme that catalyzes a chemical reaction yielding a fluorescent, chromophoric, or luminescent product, into a vector with which the donor

hematopoietic stem cells have been transfected and subsequently monitoring the corresponding signal in a tissue into which the hematopoietic stem cells have homed, such as the bone marrow. One can also observe hematopoietic stem cell engraftment by evaluation of the quantity and survival of hematopoietic stem and progenitor cells, for instance, as determined by fluorescence activated cell sorting (FACS) analysis methods known in the art. Engraftment can also be determined by measuring white blood cell counts in peripheral blood during a post-transplant period, and/or by measuring recovery of marrow cells by donor cells in a bone marrow aspirate sample.

The sections that follow provide a description of antibodies, or antigen-binding fragments thereof, that can be administered to a patient, such as a patient suffering from a cancer (such as acute myelogenous leukemia or myelodysplastic syndrome) or autoimmune disease, or a patient in need of hematopoietic stem cell transplant therapy in order to promote engraftment of hematopoietic stem cell grafts, as well as methods of administering such therapeutics to a patient (e.g., prior to hematopoietic stem cell transplantation).

Definitions

As used herein, the term "about" refers to a value that is within 10% above or below the value being described. For example, the term "about 5 nM" indicates a range of from 4.5 nM to 5.5 nM.

As used herein, the term "antibody" refers to an immunoglobulin molecule that specifically binds to, or is immunologically reactive with, a particular antigen, and includes monoclonal, genetically engineered, and otherwise modified forms of antibodies, including but not limited to chimeric antibodies, humanized antibodies, heteroconjugate antibodies (e.g., bi- tri- and quad- specific antibodies, diabodies, triabodies, and tetrabodies), and antigen binding fragments of antibodies, including, for example, Fab', F(ab')₂, Fab, Fv, IgG, and scFv fragments.

The antibodies of the present invention are generally isolated or recombinant. "Isolated," when used herein refers to a polypeptide, e.g., an antibody, that has been identified and separated and/or recovered from a cell or cell culture from which it was expressed. Ordinarily, an isolated antibody will be prepared by at least one purification step. Thus, an "isolated antibody," refers to an antibody which is substantially free of other antibodies having different antigenic specificities. For instance, an isolated antibody that specifically binds to CD1 17 is substantially free of antibodies that specifically bind antigens other than CD1 17.

Unless otherwise indicated, the term "monoclonal antibody" (mAb) is meant to include both intact molecules, as well as antibody fragments (including, for example, Fab and F(ab')₂ fragments) that are capable of specifically binding to a target protein. As used herein, the Fab and F(ab')₂ fragments refer to antibody fragments that lack the Fc fragment of an intact antibody. Examples of these antibody fragments are described herein.

Generally, antibodies comprise heavy and light chains containing antigen binding regions. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as HCVR or VH) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH1 , CH2 and CH3. Each light chain is comprised of a light chain variable region (abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The VH, and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxyl-terminus in the following order: FR1 , CDR1 , FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system.

An "intact" or "full length" antibody, as used herein, refers to an antibody having two heavy

(H) chain polypeptides and two light (L) chain polypeptides interconnected by disulfide bonds.

Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as HCVR or

VH) and a heavy chain constant region. The heavy chain constant region is comprised of three domains, CH1 , CH2 and CH3. Each light chain is comprised of a light chain variable region

(abbreviated herein as LCVR or VL) and a light chain constant region. The light chain constant region is comprised of one domain, CL. The VH, and VL regions can be further subdivided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VH and VL is composed of three CDRs and four FRs, arranged from amino-terminus to carboxyl-terminus in the following order: FR1 , CDR1 , FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies can mediate the binding of the immunoglobulin to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the classical complement system.

The terms "Fc", "Fc region," and "Fc domain," as used herein refer to the portion of an IgG antibody that correlates to a crystallizable fragment obtained by papain digestion of an IgG molecule. The Fc region comprises the C-terminal half of two heavy chains of an IgG molecule that are linked by disulfide bonds. It has no antigen binding activity but contains the carbohydrate moiety and binding sites for complement and Fc receptors, including the FcRn receptor. An Fc region contains the second constant domain CH2 (e.g., residues at EU positions 231 -340 of lgG1 ) and the third constant domain CH3 (e.g., residues at EU positions 341 -447 of human lgG1 ). As used herein, the Fc region includes the "lower hinge region" (e.g., residues at EU positions 233- 239 of lgG1 ). Fc can refer to this region in isolation, or this region in the context of an antibody, antibody fragment, or Fc fusion protein. Polymorphisms have been observed at a number of positions in Fc domains, including but not limited to EU positions 270, 272, 312, 315, 356, and 358, and thus slight differences between the sequences presented in the instant application and sequences known in the art can exist. Thus, a "wild type IgG Fc domain" or "WT IgG Fc domain" refers to any naturally occurring IgG Fc region (i.e., any allele). The sequences of the heavy chains of human lgG1 , lgG2, lgG3 and lgG4 can be found in a number of sequence databases, for example, at the Uniprot database (www.uniprot.org) under accession numbers P01857

(IGHG1_HUMAN), P01859 (IGHG2 HUMAN), P01860 (IGHG3_HUMAN), and P01861

(IGHG1_HUMAN), respectively. An example of a "WT" Fc region is provided in SEQ ID NO: 183 (which provides a heavy chain constant region containing an Fc region).

The terms "modified Fc region" or "variant Fc region" as used herein refers to an IgG Fc domain comprising one or more amino acid substitutions, deletions, insertions or modifications introduced at any position within the Fc region.

The term "antigen-binding fragment," as used herein, refers to one or more fragments of an antibody that retain the ability to specifically bind to a target antigen. The antigen-binding function of an antibody can be performed by fragments of a full-length antibody. The antibody fragments can be, for example, a Fab, F(ab')₂, scFv, diabody, a triabody, an affibody, a nanobody, an aptamer, or a domain antibody. Examples of binding fragments encompassed of the term

"antigen-binding fragment" of an antibody include, but are not limited to: (i) a Fab fragment, a monovalent fragment consisting of the V_L, V_H, C_L, and C_H1 domains; (ii) a F(ab')₂ fragment, a bivalent fragment containing two Fab fragments linked by a disulfide bridge at the hinge region; (iii) a Fd fragment consisting of the V_H and C_H1 domains; (iv) a Fv fragment consisting of the V_L and

V_H domains of a single arm of an antibody, (v) a dAb including V_H and V_L domains; (vi) a dAb fragment that consists of a V_H domain (see, e.g., Ward et al., Nature 341 :544-546, 1989); (vii) a dAb which consists of a V_H or a V_L domain; (viii) an isolated complementarity determining region (CDR); and (ix) a combination of two or more (e.g., two, three, four, five, or six) isolated CDRs which may optionally be joined by a synthetic linker. Furthermore, although the two domains of the Fv fragment, V_L and V_H, are coded for by separate genes, they can be joined, using recombinant methods, by a linker that enables them to be made as a single protein chain in which the V|_ and V_H regions pair to form monovalent molecules (known as single chain Fv (scFv); see, for example, Bird et al., Science 242:423-426, 1988 and Huston et al., Proc. Natl. Acad. Sci. USA 85:5879-5883, 1988). These antibody fragments can be obtained using conventional techniques known to those of skill in the art, and the fragments can be screened for utility in the same manner as intact antibodies. Antigen-binding fragments can be produced by recombinant DNA

techniques, enzymatic or chemical cleavage of intact immunoglobulins, or, in certain cases, by chemical peptide synthesis procedures known in the art.

As used herein, the term "anti-CD1 17 antibody" or "an antibody that binds to CD1 17" refers to an antibody that is capable of binding CD1 17 with sufficient affinity such that the antibody is useful as a diagnostic and/or therapeutic agent in targeting CD1 17.

As used herein, the term "bispecific antibody" refers to, for example, a monoclonal, often a human or humanized antibody that is capable of binding at least two different antigens. For instance, one of the binding specificities can be directed towards a hematopoietic stem cell surface antigen, CD1 17 (e.g., GNNK+ CD1 17), and the other can specifically bind a different

hematopoietic stem cell surface antigen or another cell surface protein, such as a receptor or receptor subunit involved in a signal transduction pathway that potentiates cell growth, among others.

As used herein, the term "complementarity determining region" (CDR) refers to a hypervariable region found both in the light chain and the heavy chain variable domains of an antibody. The more highly conserved portions of variable domains are referred to as framework regions (FRs). The amino acid positions that delineate a hypervariable region of an antibody can vary, depending on the context and the various definitions known in the art. Some positions within a variable domain may be viewed as hybrid hypervariable positions in that these positions can be deemed to be within a hypervariable region under one set of criteria while being deemed to be outside a hypervariable region under a different set of criteria. One or more of these positions can also be found in extended hypervariable regions. The antibodies described herein may contain modifications in these hybrid hypervariable positions. The variable domains of native heavy and light chains each contain four framework regions that primarily adopt a β-sheet configuration, connected by three CDRs, which form loops that connect, and in some cases form part of, the β- sheet structure. The CDRs in each chain are held together in close proximity by the framework regions in the order FR1 -CDR1 -FR2-CDR2-FR3-CDR3-FR4 and, with the CDRs from the other antibody chains, contribute to the formation of the target binding site of antibodies (see Kabat et al., Sequences of Proteins of Immunological Interest, National Institute of Health, Bethesda, MD., 1987). In certain embodiments, numbering of immunoglobulin amino acid residues is performed according to the immunoglobulin amino acid residue numbering system of Kabat et al., unless otherwise indicated (although any antibody numbering scheme, including, but not limited to IMGT and Chothia, can be utilized).

As used herein, the terms "condition" and "conditioning" refer to processes by which a patient is prepared for receipt of a transplant containing hematopoietic stem cells. Such

procedures promote the engraftment of a hematopoietic stem cell transplant (for instance, as inferred from a sustained increase in the quantity of viable hematopoietic stem cells within a blood sample isolated from a patient following a conditioning procedure and subsequent hematopoietic stem cell transplantation. According to the methods described herein, a patient may be

conditioned for hematopoietic stem cell transplant therapy by administration to the patient of an antibody or antigen-binding fragment thereof capable of binding an antigen expressed by

hematopoietic stem cells, such as CD1 17 (e.g., GNNK+ CD1 17). Administration of an antibody, or an antigen-binding fragment thereof, capable of binding one or more of the foregoing antigens to a patient in need of hematopoietic stem cell transplant therapy can promote the engraftment of a hematopoietic stem cell graft, for example, by selectively depleting endogenous hematopoietic stem cells, thereby creating a vacancy filled by an exogenous hematopoietic stem cell transplant.

As used herein, "CRU (competitive repopulating unit)" refers to a unit of measure of long- term engrafting stem cells, which can be detected after in-vivo transplantation.

As used herein, the term "donor" refers to a human or animal from which one or more cells are isolated prior to administration of the cells, or progeny thereof, into a recipient. The one or more cells may be, for example, a population of hematopoietic stem cells.

As used herein, the term "diabody" refers to a bivalent antibody containing two polypeptide chains, in which each polypeptide chain includes V_H and V_L domains joined by a linker that is too shoi (e.g., a linker composed of five amino acids) to allow for intramolecular association of V_H and V_L domains on the same peptide chain. This configuration forces each domain to pair with a

complementary domain on another polypeptide chain so as to form a homodimeric structure.

Accordingly, the term "triabody" refers to trivalent antibodies containing three peptide chains, each of which contains one V_H domain and one V_L domain joined by a linker that is exceedingly short (e.g., a linker composed of 1 -2 amino acids) to permit intramolecular association of V_H and V_L domains within the same peptide chain. In order to fold into their native structures, peptides configured in this way typically trimerize so as to position the V_H and V_L domains of neighboring peptide chains spatially proximal to one another (see, for example, Holliger et al., Proc. Natl. Acad. Sci. USA 90:6444-48, 1993).

As used herein, a "dual variable domain immunoglobulin" ("DVD-lg") refers to an antibody that combines the target-binding variable domains of two monoclonal antibodies via linkers to create a tetravalent, dual-targeting single agent (see, for example, Gu et al., Meth. Enzymol., 502:25-41 , 2012).

As used herein, the term "endogenous" describes a substance, such as a molecule, cell, tissue, or organ (e.g., a hematopoietic stem cell or a cell of hematopoietic lineage, such as a megakaryocyte, thrombocyte, platelet, erythrocyte, mast cell, myeoblast, basophil, neutrophil, eosinophil, microglial cell, granulocyte, monocyte, osteoclast, antigen-presenting cell,

macrophage, dendritic cell, natural killer cell, T-lymphocyte, or B-lymphocyte) that is found naturally in a particular organism, such as a human patient.

As used herein, the term "engraftment potential" is used to refer to the ability of

hematopoietic stem and progenitor cells to repopulate a tissue, whether such cells are naturally circulating or are provided by transplantation. The term encompasses all events surrounding or leading up to engraftment, such as tissue homing of cells and colonization of cells within the tissue of interest. The engraftment efficiency or rate of engraftment can be evaluated or quantified using any clinically acceptable parameter as known to those of skill in the art and can include, for example, assessment of competitive repopulating units (CRU); incorporation or expression of a marker in tissue(s) into which stem cells have homed, colonized, or become engrafted; or by evaluation of the progress of a subject through disease progression, survival of hematopoietic stem and progenitor cells, or survival of a recipient. Engraftment can also be determined by measuring white blood cell counts in peripheral blood during a post-transplant period. Engraftment can also be assessed by measuring recovery of marrow cells by donor cells in a bone marrow aspirate sample.

As used herein, the term "exogenous" describes a substance, such as a molecule, cell, tissue, or organ (e.g., a hematopoietic stem cell or a cell of hematopoietic lineage, such as a megakaryocyte, thrombocyte, platelet, erythrocyte, mast cell, myeoblast, basophil, neutrophil, eosinophil, microglial cell, granulocyte, monocyte, osteoclast, antigen-presenting cell,

macrophage, dendritic cell, natural killer cell, T-lymphocyte, or B-lymphocyte) that is not found naturally in a particular organism, such as a human patient. Exogenous substances include those that are provided from an external source to an organism or to cultured matter extracted therefrom.

As used herein, the term "framework region" or "FW region" includes amino acid residues that are adjacent to the CDRs of an antibody or antigen-binding fragment thereof. FW region residues may be present in, for example, human antibodies, humanized antibodies, monoclonal antibodies, antibody fragments, Fab fragments, single chain antibody fragments, scFv fragments, antibody domains, and bispecific antibodies, among others.

As used herein, the term "hematopoietic stem cells" ("HSCs") refers to immature blood cells having the capacity to self-renew and to differentiate into mature blood cells containing diverse lineages including but not limited to granulocytes (e.g., promyelocytes, neutrophils, eosinophils, basophils), erythrocytes (e.g., reticulocytes, erythrocytes), thrombocytes (e.g., megakaryoblasts, platelet producing megakaryocytes, platelets), monocytes (e.g., monocytes, macrophages), dendritic cells, microglia, osteoclasts, and lymphocytes (e.g., NK cells, B-cells and T-cells). Such cells may include CD34⁺ cells. CD34⁺ cells are immature cells that express the CD34 cell surface marker. In humans, CD34+ cells are believed to include a subpopulation of cells with the stem cell properties defined above, whereas in mice, HSCs are CD34-. In addition, HSCs also refer to long term repopulating HSCs (LT-HSC) and short term repopulating HSCs (ST- HSC). LT-HSCs and ST-HSCs are differentiated, based on functional potential and on cell surface marker expression. For example, human HSCs are CD34+, CD38-, CD45RA-, CD90+, CD49F+, and lin- (negative for mature lineage markers including CD2, CD3, CD4, CD7, CD8, CD10, CD1 1 B, CD19, CD20, CD56, CD235A). In mice, bone marrow LT-HSCs are CD34-, SCA-1 +, C- kit+, CD135-, Slamfl/CD150+, CD48-, and lin- (negative for mature lineage markers including Ter1 19, CD1 1 b, Gr1 , CD3, CD4, CD8, B220, IL7ra), whereas ST-HSCs are CD34+, SCA-1 +, C- kit+, CD135-, Slamfl/CD150+, and lin- (negative for mature lineage markers including Ter1 19, CD1 1 b, Gr1 , CD3, CD4, CD8, B220, IL7ra). In addition, ST-HSCs are less quiescent and more proliferative than LT-HSCs under homeostatic conditions. However, LT-HSC have greater self renewal potential (i.e., they survive throughout adulthood, and can be serially transplanted through successive recipients), whereas ST-HSCs have limited self renewal (i.e., they survive for only a limited period of time, and do not possess serial transplantation potential). Any of these HSCs can be used in the methods described herein. ST-HSCs are particularly useful because they are highly proliferative and thus, can more quickly give rise to differentiated progeny.

As used herein, the term "hematopoietic stem cell functional potential" refers to the functional properties of hematopoietic stem cells which include 1 ) multi-potency (which refers to the ability to differentiate into multiple different blood lineages including, but not limited to, granulocytes (e.g., promyelocytes, neutrophils, eosinophils, basophils), erythrocytes (e.g., reticulocytes, erythrocytes), thrombocytes (e.g., megakaryoblasts, platelet producing

megakaryocytes, platelets), monocytes (e.g., monocytes, macrophages), dendritic cells, microglia, osteoclasts, and lymphocytes (e.g., NK cells, B-cells and T-cells), 2) self-renewal (which refers to the ability of hematopoietic stem cells to give rise to daughter cells that have equivalent potential as the mother cell, and further that this ability can repeatedly occur throughout the lifetime of an individual without exhaustion), and 3) the ability of hematopoietic stem cells or progeny thereof to be reintroduced into a transplant recipient whereupon they home to the hematopoietic stem cell niche and re-establish productive and sustained hematopoiesis.

As used herein, the term "human antibody" is intended to include antibodies having variable and constant regions derived from human germline immunoglobulin sequences. A human antibody may include amino acid residues not encoded by human germline immunoglobulin sequences (e.g., mutations introduced by random or site-specific mutagenesis in vitro or during gene rearrangement or by somatic mutation in vivo). However, the term "human antibody", as used herein, is not intended to include antibodies in which CDR sequences derived from the germline of another mammalian species, such as a mouse, have been grafted onto human framework sequences. A human antibody can be produced in a human cell (for example, by recombinant expression) or by a non-human animal or a prokaryotic or eukaryotic cell that is capable of expressing functionally rearranged human immunoglobulin (such as heavy chain and/or light chain) genes. When a human antibody is a single chain antibody, it can include a linker peptide that is not found in native human antibodies. For example, an Fv can contain a linker peptide, such as two to about eight glycine or other amino acid residues, which connects the variable region of the heavy chain and the variable region of the light chain. Such linker peptides are considered to be of human origin. Human antibodies can be made by a variety of methods known in the art including phage display methods using antibody libraries derived from human immunoglobulin sequences. Human antibodies can also be produced using transgenic mice that are incapable of expressing functional endogenous immunoglobulins, but which can express human immunoglobulin genes (see, for example, PCT Publication Nos. WO 1998/24893; WO 1992/01047; WO 1996/34096; WO 1996/33735; U.S. Patent Nos. 5,413,923; 5,625,126;

5,633,425; 5,569,825; 5,661 ,016; 5,545,806; 5,814,318; 5,885,793; 5,916,771 ; and 5,939,598).

As used herein, patients that are "in need of" a hematopoietic stem cell transplant include patients that exhibit a defect or deficiency in one or more blood cell types, as well as patients having a stem cell disorder, autoimmune disease, cancer, or other pathology described herein. Hematopoietic stem cells generally exhibit 1 ) multi-potency, and can thus differentiate into multiple different blood lineages including, but not limited to, granulocytes (e.g., promyelocytes,

neutrophils, eosinophils, basophils), erythrocytes (e.g., reticulocytes, erythrocytes), thrombocytes (e.g., megakaryoblasts, platelet producing megakaryocytes, platelets), monocytes (e.g., monocytes, macrophages), dendritic cells, microglia, osteoclasts, and lymphocytes (e.g., NK cells, B-cells and T-cells), 2) self-renewal, and can thus give rise to daughter cells that have equivalent potential as the mother cell, and 3) the ability to be reintroduced into a transplant recipient whereupon they home to the hematopoietic stem cell niche and re-establish productive and sustained hematopoiesis. Hematopoietic stem cells can thus be administered to a patient defective or deficient in one or more cell types of the hematopoietic lineage in order to reconstitute the defective or deficient population of cells in vivo. For example, the patient may be suffering from cancer, and the deficiency may be caused by administration of a chemotherapeutic agent or other medicament that depletes, either selectively or non-specifically, the cancerous cell population. Additionally or alternatively, the patient may be suffering from a hemoglobinopathy (e.g., a non-malignant hemoglobinopathy), such as sickle cell anemia, thalassemia, Fanconi anemia, aplastic anemia, and Wiskott-Aldrich syndrome. The subject may be one that is suffering from adenosine deaminase severe combined immunodeficiency (ADA SCID), HIV/AIDS, metachromatic leukodystrophy, Diamond-Blackfan anemia, and Schwachman-Diamond syndrome. The subject may have or be affected by an inherited blood disorder (e.g., sickle cell anemia) or an autoimmune disorder. Additionally or alternatively, the subject may have or be affected by a malignancy, such as neuroblastoma or a hematologic cancer. For instance, the subject may have a leukemia, lymphoma, or myeloma. In some embodiments, the subject has acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma, diffuse large B-cell lymphoma, or non-Hodgkin's lymphoma. In some embodiments, the subject has myelodysplastic syndrome. In some embodiments, the subject has an autoimmune disease, such as scleroderma, multiple sclerosis, ulcerative colitis, Crohn's disease, Type 1 diabetes, or another autoimmune pathology described herein. In some embodiments, the subject is in need of chimeric antigen receptor T-cell (CART) therapy. In some embodiments, the subject has or is otherwise affected by a metabolic storage disorder. The subject may suffer or otherwise be affected by a metabolic disorder selected from the group consisting of glycogen storage diseases, mucopolysaccharidoses, Gaucher's Disease, Hurlers Disease, sphingolipidoses, metachromatic leukodystrophy, or any other diseases or disorders which may benefit from the treatments and therapies disclosed herein and including, without limitation, severe combined immunodeficiency, Wiscott-Aldrich syndrome, hyper immunoglobulin M (IgM) syndrome, Chediak-Higashi disease, hereditary lymphohistiocytosis, osteopetrosis, osteogenesis imperfecta, storage diseases, thalassemia major, sickle cell disease, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, juvenile rheumatoid arthritis and those diseases, or disorders described in "Bone Marrow Transplantation for Non-Malignant Disease," ASH Education Book, 1 :319-338 (2000), the disclosure of which is incorporated herein by reference in its entirety as it pertains to pathologies that may be treated by administration of hematopoietic stem cell transplant therapy. Additionally or alternatively, a patient "in need of" a hematopoietic stem cell transplant may one that is or is not suffering from one of the foregoing pathologies, but nonetheless exhibits a reduced level (e.g., as compared to that of an otherwise healthy subject) of one or more endogenous cell types within the hematopoietic lineage, such as megakaryocytes, thrombocytes, platelets, erythrocytes, mast cells, myeoblasts, basophils, neutrophils, eosinophils, microglia, granulocytes, monocytes, osteoclasts, antigen-presenting cells, macrophages, dendritic cells, natural killer cells, T- lymphocytes, and B- lymphocytes. One of skill in the art can readily determine whether one's level of one or more of the foregoing cell types, or other blood cell type, is reduced with respect to an otherwise healthy subject, for instance, by way of flow cytometry and fluorescence activated cell sorting (FACS) methods, among other procedures, known in the art.

As used herein, the term "recipient" refers to a patient that receives a transplant, such as a transplant containing a population of hematopoietic stem cells. The transplanted cells

administered to a recipient may be, e.g., autologous, syngeneic, or allogeneic cells.

As used herein, the term "sample" refers to a specimen (e.g., blood, blood component (e.g., serum or plasma), urine, saliva, amniotic fluid, cerebrospinal fluid, tissue (e.g., placental or dermal), pancreatic fluid, chorionic villus sample, and cells) taken from a subject.

As used herein, the term "scFv" refers to a single chain Fv antibody in which the variable domains of the heavy chain and the light chain from an antibody have been joined to form one chain. scFv fragments contain a single polypeptide chain that includes the variable region of an antibody light chain (V_L) (e.g., CDR-L1 , CDR-L2, and/or CDR-L3) and the variable region of an antibody heavy chain (V_H) (e.g., CDR-H1 , CDR-H2, and/or CDR-H3) separated by a linker. The linker that joins the V_L and V_H regions of a scFv fragment can be a peptide linker composed of proteinogenic amino acids. Alternative linkers can be used to so as to increase the resistance of the scFv fragment to proteolytic degradation (for example, linkers containing D-amino acids), in order to enhance the solubility of the scFv fragment (for example, hydrophilic linkers such as polyethylene glycol-containing linkers or polypeptides containing repeating glycine and serine residues), to improve the biophysical stability of the molecule (for example, a linker containing cysteine residues that form intramolecular or intermolecular disulfide bonds), or to attenuate the immunogenicity of the scFv fragment (for example, linkers containing glycosylation sites). It will also be understood by one of ordinary skill in the art that the variable regions of the scFv molecules described herein can be modified such that they vary in amino acid sequence from the antibody molecule from which they were derived. For example, nucleotide or amino acid substitutions leading to conservative substitutions or changes at amino acid residues can be made (e.g., in CDR and/or framework residues) so as to preserve or enhance the ability of the scFv to bind to the antigen recognized by the corresponding antibody.

As used herein, the terms "subject" and "patient" refer to an organism, such as a human, that receives treatment for a particular disease or condition as described herein. For instance, a patient, such as a human patient, may receive treatment prior to hematopoietic stem cell transplant therapy in order to promote the engraftment of exogenous hematopoietic stem cells.

As used herein, the phrase "substantially cleared from the blood" refers to a point in time following administration of a therapeutic agent (such as an anti-CD1 17 antibody, or antigen- binding fragment thereof) to a patient when the concentration of the therapeutic agent in a blood sample isolated from the patient is such that the therapeutic agent is not detectable by

conventional means (for instance, such that the therapeutic agent is not detectable above the noise threshold of the device or assay used to detect the therapeutic agent). A variety of techniques known in the art can be used to detect antibodies, antibody fragments, and protein ligands, such as ELISA-based detection assays known in the art or described herein. Additional assays that can be used to detect antibodies, or antibody fragments, include immunoprecipitation techniques and immunoblot assays, among others known in the art.

As used herein, the phrase "stem cell disorder" broadly refers to any disease, disorder, or condition that may be treated or cured by conditioning a subject's target tissues, and/or by ablating an endogenous stem cell population in a target tissue (e.g., ablating an endogenous hematopoietic stem or progenitor cell population from a subject's bone marrow tissue) and/or by engrafting or transplanting stem cells in a subject's target tissues. For example, Type I diabetes has been shown to be cured by hematopoietic stem cell transplant and may benefit from conditioning in accordance with the compositions and methods described herein. Additional disorders that can be treated using the compositions and methods described herein include, without limitation, sickle cell anemia, thalassemias, Fanconi anemia, aplastic anemia, Wiskott-Aldrich syndrome, ADA SCID, HIV/AIDS, metachromatic leukodystrophy, Diamond-Blackfan anemia, and Schwachman-Diamond syndrome. Additional diseases that may be treated using the patient conditioning and/or hematopoietic stem cell transplant methods described herein include inherited blood disorders (e.g., sickle cell anemia) and autoimmune disorders, such as scleroderma, multiple sclerosis, ulcerative colitis, and Crohn's disease. Additional diseases that may be treated using the conditioning and/or transplantation methods described herein include a malignancy, such as a neuroblastoma or a hematologic cancer, such as leukemia, lymphoma, and myeloma. For instance, the cancer may be acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma, diffuse large B-cell lymphoma, or non- Hodgkin's lymphoma. Additional diseases treatable using the conditioning and/or transplantation methods described herein include myelodysplastic syndrome. In some embodiments, the subject has or is otherwise affected by a metabolic storage disorder. For example, the subject may suffer or otherwise be affected by a metabolic disorder selected from the group consisting of glycogen storage diseases, mucopolysaccharidoses, Gaucher's Disease, Hurlers Disease,

sphingolipidoses, metachromatic leukodystrophy, or any other diseases or disorders which may benefit from the treatments and therapies disclosed herein and including, without limitation, severe combined immunodeficiency, Wiscott-Aldrich syndrome, hyper immunoglobulin M (IgM) syndrome, Chediak-Higashi disease, hereditary lymphohistiocytosis, osteopetrosis, osteogenesis imperfecta, storage diseases, thalassemia major, sickle cell disease, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, juvenile rheumatoid arthritis and those diseases, or disorders described in "Bone Marrow Transplantation for Non-Malignant Disease," ASH Education Book, 1 :319-338 (2000), the disclosure of which is incorporated herein by reference in its entirety as it pertains to pathologies that may be treated by administration of hematopoietic stem cell transplant therapy.

As used herein, the term "transfection" refers to any of a wide variety of techniques commonly used for the introduction of exogenous DNA into a prokaryotic or eukaryotic host cell, such as electroporation, lipofection, calcium- phosphate precipitation, DEAE- dextran transfection and the like.

As used herein, the terms "treat" or "treatment" refers to reducing the severity and/or frequency of disease symptoms, eliminating disease symptoms and/or the underlying cause of said symptoms, reducing the frequency or likelihood of disease symptoms and/or their underlying cause, and improving or remediating damage caused, directly or indirectly, by disease.. Beneficial or desired clinical results include, but are not limited to, promoting the engraftment of exogenous hematopoietic cells in a patient following antibody conditioning therapy as described herein and subsequent hematopoietic stem cell transplant therapy. Additional beneficial results include an increase in the cell count or relative concentration of hematopoietic stem cells in a patient in need of a hematopoietic stem cell transplant following conditioning therapy and subsequent administration of an exogenous hematopoietic stem cell graft to the patient. Beneficial results of therapy described herein may also include an increase in the cell count or relative concentration of one or more cells of hematopoietic lineage, such as a megakaryocyte, thrombocyte, platelet, erythrocyte, mast cell, myeoblast, basophil, neutrophil, eosinophil, microglial cell, granulocyte, monocyte, osteoclast, antigen-presenting cell, macrophage, dendritic cell, natural killer cell, T- lymphocyte, or B-lymphocyte, following conditioning therapy and subsequent hematopoietic stem cell transplant therapy. Additional beneficial results may include the reduction in quantity of a disease-causing cell population, such as a population of cancer cells (e.g., CD1 17+ leukemic cells) or autoimmune cells (e.g., CD1 17+ autoimmune lymphocytes, such as a CD1 17+ T-cell that expresses a T-cell receptor that cross-reacts with a self antigen). Insofar as the methods of the present invention are directed to preventing disorders, it is understood that the term "prevent" does not require that the disease state be completely thwarted. Rather, as used herein, the term preventing refers to the ability of the skilled artisan to identify a population that is susceptible to disorders, such that administration of the compounds of the present invention may occur prior to onset of a disease. The term does not imply that the disease state is completely avoided.

As used herein, the terms "variant" and "derivative" are used interchangeably and refer to naturally-occurring, synthetic, and semi-synthetic analogues of a compound, peptide, protein, or other substance described herein. A variant or derivative of a compound, peptide, protein, or other substance described herein may retain or improve upon the biological activity of the original material.

As used herein, the term "vector" includes a nucleic acid vector, such as a plasmid, a DNA vector, a plasmid, a RNA vector, virus, or other suitable replicon. Expression vectors described herein may contain a polynucleotide sequence as well as, for example, additional sequence elements used for the expression of proteins and/or the integration of these polynucleotide sequences into the genome of a mammalian cell. Certain vectors that can be used for the expression of antibodies and antibody fragments of the invention include plasmids that contain regulatory sequences, such as promoter and enhancer regions, which direct gene transcription. Other useful vectors for expression of antibodies and antibody fragments contain polynucleotide sequences that enhance the rate of translation of these genes or improve the stability or nuclear export of the mRNA that results from gene transcription. These sequence elements may include, for example, 5' and 3' untranslated regions and a polyadenylation signal site in order to direct efficient transcription of the gene carried on the expression vector. The expression vectors described herein may also contain a polynucleotide encoding a marker for selection of cells that contain such a vector. Examples of a suitable marker include genes that encode resistance to antibiotics, such as ampicillin, chloramphenicol, kanamycin, and nourseothricin. Anti-CD117 Antibodies

The present invention is based in part on the discovery of novel anti-CD1 17 antibodies and antigen binding portions thereof that are useful for therapeutic purposes. The present invention is also based in part on the discovery that antibodies, or antigen-binding fragments thereof, capable of binding CD1 17, such as GNNK+ CD1 17, can be used as therapeutic agents alone to (i) treat cancers (such as acute myelogenous leukemia or myelodysplastic syndrome) and autoimmune diseases characterized by CD1 17+ cells and (ii) promote the engraftment of transplanted hematopoietic stem cells in a patient in need of transplant therapy. These therapeutic activities can be caused, for instance, by the binding of anti-CD1 17 antibodies, or antigen-binding fragments thereof, to CD1 17 (e.g., GNNK+ CD1 17) expressed on the surface of a cell, such as a cancer cell, autoimmune cell, or hematopoietic stem cell and subsequently inducing cell death. The depletion of endogenous hematopoietic stem cells can provide a niche toward which transplanted hematopoietic stem cells can home, and subsequently establish productive hematopoiesis. In this way, transplanted hematopoietic stem cells may successfully engraft in a patient, such as human patient suffering from a stem cell disorder described herein.

Antibodies and antigen-binding fragments capable of binding human CD1 17 (also referred to as c-Kit, mRNA NCBI Reference Sequence: NM_000222.2, Protein NCBI Reference Sequence: NP 000213.1 ), including those capable of binding GNNK+ CD1 17, can be used in conjunction with the compositions and methods described herein in order to condition a patient for

hematopoietic stem cell transplant therapy. Polymorphisms affecting the coding region or extracellular domain of CD1 17 in a significant percentage of the population are not currently well- known in non-oncology indications. There are at least four isoforms of CD1 17 that have been identified, with the potential of additional isoforms expressed in tumor cells. Two of the CD1 17 isoforms are located on the intracellular domain of the protein, and two are present in the external juxtamembrane region. The two extracellular isoforms, GNNK+ and GNNK-, differ in the presence (GNNK+) or absence (GNNK-) of a 4 amino acid sequence. These isoforms are reported to have the same affinity for the ligand (SCF), but ligand binding to the GNNK- isoform was reported to increase internalization and degradation. The GNNK+ isoform can be used as an immunogen in order to generate antibodies capable of binding CD1 17, as antibodies generated against this isoform will be inclusive of the GNNK+ and GNNK- proteins.

The disclosure provides novel anti-CD1 17 antibodies whose heavy and light chain amino acid sequences are provided in Table 1 , Table 5, Table 7, and Table 10. Thus, included in the disclosure are anti-CD1 17 antibodies comprising binding regions (heavy and light chain CDRs or variable regions) as set forth in SEQ ID Nos: 7 to 168. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 8. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 9. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 10. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 1 1 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 12. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 13. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 14. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 15. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 16. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 17. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 18. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 19. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 20. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 21 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 22. In one embodiment, the anti- CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 23. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 24, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 25. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 26, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 27. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

28, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 29. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 30, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 31 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 32, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 33. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 34, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO:35. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 36, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 37. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 38, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 39. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

40, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 41 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 32, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 42. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 43, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 44. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 45, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 46. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 47, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 48. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 49, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 50. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

51 , and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 52. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 53, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 54. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 55, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 56. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 57, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 58. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 9, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 60. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 61 , and a light chain variable region as set forth in the amino acid sequence of SEQ

62, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 63. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 64, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 65. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 66, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 67. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 68, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 69. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 70, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 71 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 72, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 73. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

74, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 75. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 76, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 77. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 78, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 79. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 80, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 81 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 82, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 83. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 84, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 85. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

86, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 87. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 88. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 89. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 90. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 91 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

NO: 92. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 93. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 94. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO:95. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 96.

In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 97. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 97. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 143, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 144. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 151 , and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 152. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 143, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 156. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of

SEQ ID NO: 158, and a light chain variable region as set forth in the amino acid sequence of SEQ

ID NO: 156. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO:

160, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 152.

In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 98, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 99. In one

embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 99. In one embodiment, the anti-

CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 7, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 100. In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 98, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 101 . In one embodiment, the anti-CD1 17 antibody, or antigen binding portion thereof, comprises a heavy chain variable region as set forth in the amino acid sequence of SEQ ID NO: 98, and a light chain variable region as set forth in the amino acid sequence of SEQ ID NO: 102.

In one embodiment, the antibody is an intact antibody comprising a heavy chain and a light chain variable region as set forth in Table 1 . In one embodiment, the anti-CD1 17 antibody is engineered to have a short half life.

Table 1 . Antibody heavy and light chain variable region amino acid sequences

Antibody Type of

name Chain Amino acid sequence

NO: 7)

AIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAP KLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-4 h Kappa QFNSYPLTFGGGTKVDIK (SEQ ID NO: 1 1 )

QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIGWVRQMPGK GLEWMGIIYPGDSDTRYSPSFQGQVTISAGKSISTAYLQWSSLKA SDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID

HC-5 hlgG1 NO: 7)

NIQMTQSPSSLSASVGDRVTITCRASQAISDYLAWFQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-5 h Kappa QLNSYPLTFGGGTKVEIK (SEQ ID NO: 12)

HC-6 hlgG1 NO: 7)

AIRMTQSPSSLSASVGDRVIIACRASQGIGGALAWYQQKPGNAP KVLVYDASTLESGVPSRFSGGGSGTDFTLTISSLQPEDFATYYC

LC-6 h Kappa QQFNSYPLTFGGGTKLEIK (SEQ ID NO: 13)

HC-7 hlgG1 NO: 7)

DIAMTQSPPSLSAFVGDRVTITCRASQGIISSLAWYQQKPGKAPK LLIYDASSLESGVPSRFSGSGSGTDFTLTIRSLQPEDFATYYCQQ

LC-7 h Kappa FNSYPLTFGGGTKLEIK (SEQ ID NO: 14)

HC-8 hlgG1 NO: 7)

DIQMTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKAGKAP KVLISDASSLESGVPSRFSGSGSGTDFTLSISSLQPEDFATYYCQ

LC-8 h Kappa QFNGYPLTFGGGTKVDIK (SEQ ID NO: 15)

QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIGWVRQMPGK GLEWMGIIYPGDSDTRYSPSFQGQVTISAGKSISTAYLQWSSLKA

HC-9 hlgG1 SDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID Antibody Type of

name Chain Amino acid sequence

NO: 7)

AIRMTQSPSSLSASVGDRVTITCQASQGIRNDLGWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCQQ

LC-9 h Kappa FNSYPLTFGGGTKLEIK (SEQ ID NO: 16)

HC-10 hlgG1 NO: 7)

NIQMTQSPSSLSTSVGDRVTITCRASQGIGTSLAWYQQKPGKPP KLLIYDASSLESGVPSRLSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-10 h Kappa QSNSYPITFGQGTRLEIK (SEQ ID NO: 17)

HC-1 1 hlgG1 NO: 7)

AIQLTQSPSSLSASVGDRVTITCRASQSIGDYLTWYQQKPGKAPK VLIYGASSLQSGVPPRFSGSGSGTDFTLTVSSLQPEDFATYYCQ

LC-1 1 h Kappa QLNSYPLTFGGGTKLEIK (SEQ ID NO: 18)

HC-12 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGVRSTLAWYQQKPGKAP KLLIYDASILESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

LC-12 h Kappa FNGYPLTFGQGTRLEIK (SEQ ID NO: 19)

HC-13 hlgG1 NO: 7)

DIVMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAP KLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-13 h Kappa QFNSYPLTFGGGTKLEIK (SEQ ID NO: 20)

HC-14 hlgG1 SDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID Antibody Type of

name Chain Amino acid sequence

NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGISSFLAWYQQKPGKAPK LLIYDASTLQSGVPSRFSGSASGTDFTLTISSLQPEDFATYYCQQ

LC-14 h Kappa LNGYPLTFGGGTKVEIK (SEQ ID NO: 21 )

HC-15 hlgG1 NO: 7)

AIQLTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQKPGIGPK LLIYDASTLESGVPARFSGSGSRTDFTLTITSLQPEDFATYYCQQ

LC-15 h Kappa FNGYPLTFGGGTKLEIK (SEQ ID NO: 22)

HC-16 hlgG1 NO: 7)

AIQLTQSPSSLSASVGDRVTITCRASQGITSALAWYQEKPGKAPN LLIYDASSLESGVPSRFSGSGYGTDFTLTISSLQPEDFATYYCQQ

LC-16 h Kappa LNSYPLTFGGGTKVDIK (SEQ ID NO: 23)

QIQLVQSGPELRKPGESVKISCKASGYTFTDYAMYWVKQAPGK GLKWMGWINTYTGKPTYADDFKGRFVFSLEASANTANLQISNLK NEDTATYFCARARGLVDDYVMDAWGQGTSVTVSS (SEQ ID NO:

HC-17 hlgG1 24)

SYELIQPPSASVTLGNTVSLTCVGDELSKRYAQWYQQKPDKTIV SVIYKDSERPSGISDRFSGSSSGTTATLTIHGTLAEDEADYYCLST

LC-17 hLambda YSDDNLPVFGGGTKLTVL (SEQ ID NO: 25)

EVQLQQYGAELGKPGTSVRLSCKVSGYNIRNTYIHWVNQRPGE GLEWIGRIDPTNGNTISAEKFKTKATLTADTSSHTAYLQFSQLKS

HC-18 hlgG1 DDTAIYFCALNYEGYADYWGQGVMVTGSS (SEQ ID NO: 26)

DIQMTQSPSFLSASVGDRVTINCKASQNINKYLNWYQQKVGEAP KRLIFKTNSLQTGIPSRFSGSGSGTDYTLTISSLQTEDVATYFCFQ

LC-18 h Kappa YNIGYTFGAGTKVELK (SEQ ID NO: 27)

EVQLQESGPGLVKPSQSLSLTCSVTGYSISSNYRWNWIRKFPGN KVEWMGYINSAGSTNYNPSLKSRISMTRDTSKNQFFLQVNSVTT EDTATYYCARSLRGYITDYSGFFDYWGQGVMVTVSS (SEQ ID

HC-19 hlgG1 NO: 28) Antibody Type of

name Chain Amino acid sequence

DIRMTQSPASLSASLGETVNIECLASEDIFSDLAWYQQKPGKSPQ LLIYNANSLQNGVPSRFSGSGSGTRYSLKINSLQSEDVATYFCQ

LC-19 h Kappa QYKNYPLTFGSGTKLEIK (SEQ ID NO: 29)

EVQLQQYGAELGKPGTSVRLSCKLSGYKIRNTYIHWVNQRPGK GLEWIGRIDPANGNTIYAEKFKSKVTLTADTSSNTAYMQLSQLKS

HC-20 hlgG1 DDTALYFCAMNYEGYEDYWGQGVMVTVSS (SEQ ID NO: 30)

DIQMTQSPSFLSASVGDSVTINCKASQNINKYLNWYQQKLGEAP KRLIHKTDSLQTGIPSRFSGSGSGTDYTLTISSLQPEDVATYFCFQ

LC-20 h Kappa YKSGFMFGAGTKLELK (SEQ ID NO: 31 )

QIQLVQSGPELKKPGESVKISCKASGYTFTDYAVYWVIQAPGKGL KWMGWINTYTGKPTYADDFKGRFVFSLETSASTANLQISNLKNE

HC-21 hlgG1 DTATYFCARGAGMTKDYVMDAWGRGVLVTVS (SEQ ID NO: 32)

SYELIQPPSASVTLGNTVSLTCVGDELSKRYAQWYQQKPDKTIV SVIYKDSERPSDISDRFSGSSSGTTATLTIHGTLAEDEADYYCLST

LC-21 hLambda YSDDNLPVFGGGTKLTVL (SEQ ID NO: 33)

QVQLKESGPGLVQPSQTLSLTCTVSGFSLTSYLVHWVRQPPGK TLEWVGLMWNDGDTSYNSALKSRLSISRDTSKSQVFLKMHSLQ

HC-22 hlgG1 AE DTATYYC AR ES N LG FTYWG HGTL VT VSS (SEQ ID NO: 34)

DIQMTQSPASLSASLEEIVTITCKASQGIDDDLSWYQQKPGKSPQ LLIYDVTRLADGVPSRFSGSRSGTQYSLKISRPQVADSGIYYCLQ

LC-22 h Kappa SYSTPYTFGAGTKLELK (SEQ ID NO: 35)

EVQLQQYGAELGKPGTSVRLSCKVSGYNIRNTYIHWVHQRPGE GLEWIGRIDPTNGNTISAEKFKSKATLTADTSSNTAYMQFSQLKS

HC-23 hlgG1 DDTAIYFCAMNYEGYADYWGQGVMVTVSS (SEQ ID NO: 36)

DIQMTQSPSFLSASVGDRLTINCKASQNINKYLNWYQQKLGEAP KRLIFKTNSLQTGIPSRFSGSGSGTDYTLTISSLQPEDVATYFCFQ

LC-23 h Kappa YNIGFTFGAGTKLELK (SEQ ID NO: 37)

EVQLVESGGGLVQSGRSLKLSCAASGFTVSDYYMAWVRQAPTK GLEWVATINYDGSTTYHRDSVKGRFTISRDNAKSTLYLQMDSLR SEDTATYYCARHGDYGYHYGAYYFDYWGQGVMVTVSS (SEQ

HC-24 hlgG1 ID NO: 38)

DIVLTQSPALAVSLGQRATISCRASQTVSLSGYNLIHWYQQRTGQ QPKLLIYRASNLAPGIPARFSGSGSGTDFTLTISPVQSDDIATYYC

LC-24 h Kappa QQSRESWTFGGGTNLEMK (SEQ ID NO: 39)

HC-25 hlgG1 QIQLVQSGPELKKPGESVKISCKASGYTFTDYAIHWVKQAPGQG Antibody Type of

name Chain Amino acid sequence

LRWMAWINTETGKPTYADDFKGRFVFSLEASASTAHLQISNLKN EDTATFFCAGGSHWFAYWGQGTLVTVSS (SEQ ID NO: 40)

SYELIQPPSASVTLENTVSITCSGDELSNKYAHWYQQKPDKTILE VIYNDSERPSGISDRFSGSSSGTTAILTIRDAQAEDEADYYCLSTF

LC-25 hLambda SDDDLPIFGGGTKLTVL (SEQ ID NO: 41 )

HC-26 hlgG1 DTATYFCARGAGMTKDYVMDAWGRGVLVTVS (SEQ ID NO: 32)

SYELIQPPSTSVTLGNTVSLTCVGNELPKRYAYWFQQKPDQSIV RLIYDDDRRPSGISDRFSGSSSGTTATLTIRDAQAEDEAYYYCHS

LC-26 hLambda TYTDDKVPIFGGGTKLTVL (SEQ ID NO: 42)

EVQLVESGGGLVQPGRSMKLSCKASGFTFSNYDMAWVRQAPT RGLEWVASISYDGITAYYRDSVKGRFTISRENAKSTLYLQLVSLR SEDTATYYCTTEGGYVYSGPHYFDYWGQGVMVTVSS (SEQ ID

HC-27 hlgG1 NO: 43)

DIQMTQSPSSMSVSLGDTVTITCRASQDVGIFVNWFQQKPGRSP RRMIYRATNLADGVPSRFSGSRSGSDYSLTISSLESEDVADYHC

LC-27 h Kappa LQYDEFPRTFGGGTKLELK (SEQ ID NO: 44)

EVQLQQYGAELGKPGTSVRLSCKVSGYKIRNTYIHWVNQRPGK GLEWIGRIDPANGNTIYAEKFKSKVTLTADTSSNTAYMQLSQLKS

HC-28 hlgG1 DDTALYFCAMNYEGYEDYWGQGVMVTVSS (SEQ ID NO: 45)

DIQMTQSPSFLSASVGDSVTINCKASQNINKYLNWYQQKLGEAP KRLIHKTNSLQPGFPSRFSGSGSGTDYTLTISSLQPEDVAAYFCF

LC-28 h Kappa QYNSGFTFGAGTKLELK (SEQ ID NO: 46)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIHWVRQAPGQ GLEWMGWMNPHSGDTGYAQKFQGRVTMTRDTSTSTVYMELSS LRSEDTAVYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS

HC-29 hlgG1 (SEQ ID NO: 47)

DIQMTQSPSSLSASVGDRVTITCRASQGIGNELGWYQQKPGKAP KLLIYAASNLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-29 h Kappa QYDNLPLTFGQGTKVEIK (SEQ ID NO: 48)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPG QGLEWMGWINPNSGDTNYAQNFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS

HC-30 hlgG1 (SEQ ID NO: 49) Antibody Type of

name Chain Amino acid sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAP KLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-30 h Kappa QLNGYPLTFGGGTKVEIK (SEQ ID NO: 50)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLHWVRQAPG QGLEWMGWINPNSGGTNYAQKFQGRVTMTRDTSTSTVYMELS SLRSEDTAVYYCARHGRGYEGYEGAFDIWGQGTLVTVSSAS

HC-31 hlgG1 (SEQ ID NO: 51 )

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAP KLLIYDASELETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-31 h Kappa QLNGYPITFGQGTKVEIK (SEQ ID NO: 52)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ GLEWMGWLNPSGGGTSYAQKFQGRVTMTRDTSTSTVYMELSS LRSEDTAVYYCARHGRGYDGYEGAFDIWGQGTLVTVSSAS

HC-32 hlgG1 (SEQ ID NO: 53)

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-32 h Kappa QLNGYPLTFGGGTKVEIK (SEQ ID NO: 54)

QVQLVQSGAEVKKPGASVKVSCKASGYTFSTYYMHWVRQAPG QGLEWMGIINPSGGSTSYAQKFQGRVTMTRDTSTSTVYMKLSSL RSEDTAVYYCARHGRGYEGYEGAFDIWGQGTLVTVSSAS (SEQ

HC-33 hlgG1 ID NO: 55)

DIQMTQSPSSLSASVGDRVTITCRASQGIRDDLGWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-33 h Kappa QANGFPLTFGGGTKVEIK (SEQ ID NO: 56)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIHWVRQAPGQ GLEWMGIINPSGGNTNYAQNFQGRVTMTRDTSTSTVYMELSSL RSEDTAVYYCARHGRGYNAYEGAFDIWGQGTLVTVSSAS (SEQ

HC-34 hlgG1 ID NO: 57)

LC-34 h Kappa QVNGYPLTFGGGTKVEIK (SEQ ID NO: 58)

QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAISWVRQAPGQ GLEWMGVINPTVGGANYAQKFQGRVTMTRDTSTSTVYMELSSL RSEDTAVYYCARHGRGYNEYEGAFDIWGQGTLVTVSSAS (SEQ

HC-35 hlgG1 ID NO: 59) Antibody Type of

name Chain Amino acid sequence

DIQMTQSPSSLSASVGDRVTITCQASQDISDYLNWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-35 h Kappa QGNSFPLTFGGGTKLEIK (SEQ ID NO: 60)

QVQLVQSGAEVKKLGASVKVSCKASGYTFSSYYMHWVRQAPG QGLEWMGVINPNGAGTNFAQKFQGRVTMTRDTSTSTVYMELSS LRSEDTAVYYCARHGRGYEGYEGAFDIWGQGTLVTVSSAS

HC-36 hlgG1 (SEQ ID NO: 61 )

LC-36 h Kappa QLNGYPLTFGGGTKVEIK (SEQ ID NO: 50)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMHWVRQAPG QG LEW MGW I N PTGGGTN YAQN FQG R VTMTRDTSTST VYME LS SLRSEDTAVYYCARHGRGYEGYEGAFDIWGQGTLVTVSSAS

HC-37 hlgG1 (SEQ ID NO: 62)

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDVSWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-37 h Kappa QLSGYPITFGQGTKLEIK (SEQ ID NO: 63)

QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIHWVRQAPGQ GLEWMGMINPSGGSTNYAQKFQGRVTMTRDTSTSTVYMELSSL RSEDTAVYYCARHGRGYNDYEGAFDIWGQGTLVTVSSAS (SEQ

HC-38 hlgG1 ID NO: 64)

DIQMTQSPSSLSASVGDRVTITCRASQSISDWLAWYQQKPGKAP KLLIYEASNLEGGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-38 h Kappa QANSFPYTFGQGTKVEIK (SEQ ID NO: 65)

QVQLVQSGAEVKKPGASVKVSCKASGYIFSAYYIHWVRQAPGQ GLEWMGIINPSGGSTRYAQKFQGRVTMTRDTSTSTVYMELSSLR SEDTAVYYCARHGRGYGGYEGAFDIWDQGTLVTVSSAS (SEQ

HC-39 hlgG1 ID NO: 66)

DIQMTQSPSSLSASVGDRVTITCRASQGIGDYVAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-39 h Kappa QLNGYPITFGQGTRLEIK (SEQ ID NO: 67)

EVQLVQSGAEVKKPGESLKISCKGSGYRFTSYWIGWVRQMPGK GLEWMGIIYPDDSDTRYSPSFQGQVTISVDKSNSTAYLQWSSLK ASDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS (SEQ

HC-40 hlgG1 ID NO: 68) Antibody Type of

name Chain Amino acid sequence

DIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTYFTLTISSLQPEDFATYYCQ

LC-40 h Kappa QGASFPITFGQGTKVEIK (SEQ ID NO: 69)

EVQLVQSGAEVKKPGESLKISCKGSGSSFPNSWIAWVRQMPGK GLEWMGIIYPSDSDTRYSPSFQGQVTISADKSISTAYLQWSSLEA SDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-41 hlgG1 NO: 70)

DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWYQQKPGKAP KLLIYDASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-41 h Kappa QLNSYPLTFGGGTKVEIK (SEQ ID NO: 71 )

EVQLVQSGAEVKKPGESLKISCKGSGYSFDSYWIGWVRQMPGK GLEWMGIMYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLK ASDTAMYYCARHGRGYNAYEGAFDIWGQGTLVTVSSAS (SEQ

HC-42 hlgG1 ID NO: 72)

DIQMTQSPSSLSASVGDRVTITCRASQSINNWLAWYQQKPGKAP KLLIYDAFILQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQ

LC-42 h Kappa LNSYPLTFGPGTKVDIK (SEQ ID NO: 73)

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNWIAWVRQMPGKG LEWMGIIYPGDSETRYSPSFQGQVTISADKSISTAYLQWSSLKAS DTAMYYCARHGRGYYGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-43 hlgG1 NO: 74)

DIQMTQSPSSLSASVGDRVTITCRASQGISDNLNWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-43 h Kappa QAISFPLTFGQGTKVEIK (SEQ ID NO: 75)

EVQLVQSGAEVKKPGESLKISCKGSGYNFTSYWIGWVRQMPGK GLEWMGVIYPDDSETRYSPSFQGQVTISADKSISTAYLQWSSLK ASDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS (SEQ

HC-44 hlgG1 ID NO: 76)

DIQMTQSPSSLSASVGDRVTITCRASRDIRDDLGWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-44 h Kappa QANSFPLTFGGGTKVEIK (SEQ ID NO: 77)

EVQLVQSGAEVKKPGESLKISCKGSGYTFNTYIGWVRQMPGKG LEWMGIIYPGDSGTRYSPSFQGQVTISADKAISTAYLQWSSLKAS DTAMYYCARHSRGYNGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-45 hlgG1 NO: 78) Antibody Type of

name Chain Amino acid sequence

DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-45 h Kappa QANSFPVTFGQGTKVEIK (SEQ ID NO: 79)

EVQLVQSGAEVKKPGESLKISCKGSGYNFTTYWIGWVRQMPGK GLEWMGIIHPADSDTRYNPSFQGQVTISADKSISTAYLQWSSLKA SDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-46 hlgG1 NO: 80)

DIQMTQSPSSLSASVGDRVTITCRVSQGISSYLAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-46 h Kappa QANSFPLTFGGGTKVEIK (SEQ ID NO: 81 )

EVQLVQSGAEVKKPGESLKISCKGSGYRFSNYWIAWVRQMPGK GLEWMGIIYPDNSDTRYSPSFQGQVTISADKSISTAYLQWSSLKA SDTAMYYCARHGRGYDGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-47 hlgG1 NO: 82)

DIQMTQSPSSLSASVGDRVTITCRASQGIRSDLAWYQQKPGKAP KLLIYGASSLQSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-47 h Kappa QANSFPLSFGQGTKVEIK (SEQ ID NO: 83)

EVQLVQSGAEVKKPGESLKISCKGSGYRFASYWIGWVRQMPGK GLEWMGITYPGDSETRYNPSQGQVTISADKSISTAYLQWSSLKA SDTAMYYCARHGRGYGGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-48 hlgG1 NO: 84)

LC-48 h Kappa QANSFPLTFGGGTKVEIK (SEQ ID NO: 85)

EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGK GLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKA SDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSSAS (SEQ ID

HC-49 hlgG1 NO: 86)

DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-49 h Kappa QTNSFPLTFGQGTRLEIK (SEQ ID NO: 87)

HC-74 hlgG1 NO: 7) Antibody Type of

name Chain Amino acid sequence

DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQQKPGKAP KLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-74 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 88)

HC-75 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGIRSALAWYQQKPGKAP KLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-75 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 89)

HC-76 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWYQQKPGKAP KLLIYDASSLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-76 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 90)

HC-77 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQQKPGKAP KLLIYDASILESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

LC-77 h Kappa FNSYPLTFGGGTKVEIK (SEQ ID NO: 91 )

HC-78 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGIRSALAWYQQKPGKAP KLLIYDASILESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

LC-78 h Kappa FNSYPLTFGGGTKVEIK (SEQ ID NO: 92)

HC-79 hlgG1 NO: 7) Antibody Type of

name Chain Amino acid sequence

DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWYQQKPGKAP KLLIYDASILESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

LC-79 h Kappa FNSYPLTFGGGTKVEIK (SEQ ID NO: 93)

HC-80 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAP KLLIYDASILESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQ

LC-80 h Kappa FNSYPLTFGGGTKVEIK (SEQ ID NO: 94)

HC-81 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQQKPGKAP KLLIYDASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-81 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 95)

HC-82 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGIRSALAWYQQKPGKAP KLLIYDASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-82 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 96)

HC-83 hlgG1 NO: 7)

DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWYQQKPGKAP KLLIYDASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-83 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 97)

HC-84 hlgG1 NO: 7) Antibody Type of

name Chain Amino acid sequence

LC-84 h Kappa QFNSYPLTFGGGTKVEIK (SEQ ID NO: 97)

EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGWVRQMPGK GLEWMGIIYPGDSDTRYSPSFQGQVTISADKSISTAYLQWSSLKA SDTAMYYCARHGLGYNGYEGAFDIWGQGTLVTVSS (SEQ ID

HC-245 hlgG1 NO: 98)

DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQKPGKAP KLLIYDASTLESGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-245 h Kappa QFNGYPLTFGQGTRLEIK (SEQ ID NO: 99)

HC-246 hlgG1 NO: 7)

LC-246 h Kappa QFNGYPLTFGQGTRLEIK (SEQ ID NO: 99)

HC-247 hlgG1 NO: 7)

DIQMTQSPSSLSASVGDRVTITCRASRGISDYLAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-247 h Kappa QANSFPITFGQGTRLEIK (SEQ ID NO: 100)

HC-248 hlgG1 NO: 98)

LC-248 h Kappa QLNGYPLTFGQGTRLEIK (SEQ ID NO: 101 )

HC-249 hlgG1 NO: 98) Antibody Type of

name Chain Amino acid sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQKPGKAP KLLIYDASNLETGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQ

LC-249 h Kappa QLNGYPLTFGQGTRLEIK (SEQ ID NO: 102)

The nucleic acid sequences corresponding to the heavy and light chain regions of certain sequences described above are provided in Table 2.

Table 2. Heavy and light chain antibody variable region nucleic acid sequences

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-l hlgGl

GATAGTAA (SEQ ID NO: 103)

GCCATTCAACTTACACAAAGTCCGAGTAGTCTCAGCGCGAGCGTCGGGGACC G G GTA ACC AT AACTTG CCG AG CC AG CC AG G G CGTCTCTAG CG C ATTG G C ATG GTATCAACAAAAACCTGGAAAGGCTCCCAAGCTCCTCATTTACGATGCTAGCT CCCTTGAATCTGGCGTACCATCCCGCTTTAGTGGCAGTGGGTCTGGAACAGAC TTTACTCTTACAATATCATCCCTGCAACCAGAAGA I 1 1 1 GCTACCTACTACTGTC A AC AGTTTA ATAGTTACCC ACTC AC ATTCG G CG G G G GTACG AA AGT AG A A ATA AAGCGAACCGTGGCTGCGCCTAGCGTCTTTATCTTTCCCCCGAGCGATGAACA GTTG AA ATC AG G AACTG CTTCTGTG GTATGTTTG CTTA ATA A 1 1 1 1 I ACCCACG G G A AG C AA AAGTG C AGTG G AA AGT AG AC A ATG CG CTCC AGTCCG G C AATTCT

LC-1 hKappa

CAAGAGAGTGTGACTGAACAGGATTCTAAGGATAGCACTTATTCACTGTCAAG TACCTTGACATTGTCAAAGGCGGACTATGAGAAACATAAGGTTTACGCCTGTG

AG GTA AC AC ACC A AG G G CTC AG CTC ACCTGTT ACG AA ATCCTTC A AT AG G G G C GAGTGT (SEQ ID NO: 104)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-2 hlgGl

GATAGTAA (SEQ ID NO: 103)

GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGAGACAG

AGTC ACC ATC ACTTG CCGG G C A AGTC AG G G C ATTAG AACTGATTT AG G CTG GT

ATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGT

TTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGTTTAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAAATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-2 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 105)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AAA AACCTG G CG AA AG C

CTG AAA ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

HC-3 hlgGl

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

GATAGTAA (SEQ ID NO: 103)

GCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAG

AGTCACCATCACTTGCCGGGCAAGTCAGGGCATTAGAAATGATTTAGCCTGGT

ATCAGCAGAAACCAGGGAAAACTCCTAAGCTCCTGATCTATGATGCCTCCAGT

TTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGTTTAATAGTTACCCGCTCACTTTCGGCGGAGGGACCAAGGTGGAGAT

CAAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGC

AG CTG A AGTCTG GCACCGCCAGCGTG GTGTG CCTG CTG A AC AACTTCTACCCC

CGCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAAC

AGCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTG

AGCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACG

CCTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAA

LC-3 hKappa

CCGGGGCGAGTGCTAA (SEQ I D NO: 106)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

HC-4 hlgGl

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG GATAGTAA (SEQ ID NO: 103)

GCCATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAG

AGTC ACC ATC ACTTG CCGG G C A AGTC AG G G C ATTAG AA ATG ATTTAG G CTG GT

ATCAACAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGATGCCTCCAGT

TTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGTTTAATAGTTACCCTCTGACTTTCGGCGGAGGGACCAAAGTGGATATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-4 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 107)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AAA ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-5 hlgGl

GATAGTAA (SEQ ID NO: 103)

AACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATCTGTGGGAGACAG

AGTC ACC ATC ACTTGTCG G G CG AGTC AG G CC ATTAG CG ATT ATTTAG CCTG GT

TTCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAAT

TTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGCTTAATAGTTACCCCCTCACTTTCGGCGGAGGGACCAAGGTGGAGATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

LC-5 hKappa

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC CGGGGCGAGTGCTAA (SEQ ID NO: 108)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-6 hlgGl

GATAGTAA (SEQ ID NO: 103)

GCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGGGACAG

AGTCATTATCGCTTGCCGGGCAAGTCAGGGCATCGGCGGTGCTTTAGCCTGGT

ATC AG C AG A AACC AG G G A ATG CTCCTA AG GTCCTG GTCTATG ATG CCTCC ACT

TTGGAAAGTGGGGTCCCATCACGGTTCAGCGGCGGTGGATCTGGGACAGATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTACTACTGTC

AACAGTTTAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGCTGGAGATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-6 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 109)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AAA AACCTG G CG AA AG C

CTG AAA ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

HC-7 hlgGl

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

GATAGTAA (SEQ ID NO: 103)

GACATCGCGATGACCCAGTCTCCACCCTCCCTGTCTGCATTTGTAGGGGACAG

AGTC ACC ATC ACTTG CCGG G C A AGTC AG G G C ATTATC AGTTCTTTAG CCTG GT

ATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAGT

TTGGAAAGTGGGGTCCCATCAAGGTTCAGTGGCAGTGGATCTGGGACAGATT

TCACTCTCACCATCCGCAGCCTGCAGCCTGAAGA I 1 1 1 GCCACTTATTACTGTC

AACAGTTTAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGCTGGAGATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-7 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 110)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

HC-8 hlgGl

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG GATAGTAA (SEQ ID NO: 103)

GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCGTCTGTTGGAGACAG

AGTC ACC ATC ACTTG CCGG G C A AGTC AG G G C ATTAG C AGTG CTTTAG CCTG GT

ATCAGCAGAAAGCAGGGAAAGCTCCTAAAGTCCTGATCTCTGATGCCTCCAGT

TTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATT

TC ACTCTC AG CATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGTTTAATGGTTACCCGCTCACTTTCGGCGGAGGGACCAAAGTGGATATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-8 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 111)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AAA ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-9 hlgGl

GATAGTAA (SEQ ID NO: 103)

GCCATCCGGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAG

AGTCACCATCACTTGCCAGGCGAGTCAGGGCATTAGAAATGATTTAGGCTGGT

ATCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTACGATGCATCCAAT

TTGGAAACAGGGGTCCCATCAAGGTTCAGTGGAAGTGGATCTGGGACAGATT

TT ACTTTC ACC ATC AG C AG CCTG C AG CCTG A AG ATATTG C A AC AT ATTACTGTC

AACAGTTTAATAGTTACCCGCTCACTTTCGGCGGAGGGACCAAGCTGGAGATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

LC-9 hKappa

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC CGGGGCGAGTGCTAA (SEQ ID NO: 112)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-10 hlgGl

GATAGTAA (SEQ ID NO: 103)

AACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTACATCCGTAGGAGACAG

AGTC ACC ATC ACTTG CCGG G C A AGTC AG G G C ATTG G C ACTTCTTT AG CCTG GT

ATCAGCAGAAGCCAGGGAAGCCTCCTAAGTTACTGATCTATGATGCCTCCAGT

TTGGAAAGTGGGGTCCCATCAAGGCTCAGCGGCAGTGGATCTGGGACAGATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGTCTAATAGTTATCCGATCACCTTCGGCCAAGGGACACGACTGGAGATT

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-10 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 113)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AAA AACCTG G CG AA AG C

CTG AAA ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

HC-11 hlgGl

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

GATAGTAA (SEQ ID NO: 103)

GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGA

GTCACCATCACTTGCCGGGCAAGTCAGAGCATTGGCGACTATTTGACTTGGTA

TCAGCAGAAACCAGGCAAAGCCCCTAAGGTCCTGATCTATGGTGCATCCAGTT

TGCAAAGTGGGGTCCCACCAAGGTTCAGTGGCAGTGGTTCTGGGACAGATTT

CACTCTCACCGTCAGCAGTCTGCAACCTGAAGA I 1 1 1 GCAACTTATTACTGTCA

ACAGCTTAATAGTTACCCCCTCACTTTCGGCGGAGGGACCAAGCTGGAGATCA

AACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCAG

CTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCCG

CGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACAG

CCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGAG

CAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGCC

TGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAACC

LC-11 hKappa

GGGGCGAGTGCTAA (SEQ ID NO: 114)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

HC-12 hlgGl

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

GATAGTAA (SEQ ID NO: 103)

GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAG

AGTC ACC ATC ACGTG CCG G G C A AGTC AG G G CGTT AG G AGT ACTTT AG CCTG G

TATCAGCAGAAACCAGGGAAAGCTCCTAAGCTCCTGATCTATGATGCCTCCAT

TTTGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGAT

TTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGA I 1 1 1 GCAACTTATTACTGT

CAACAGTTTAATGGTTACCCTCTCACCTTCGGCCAAGGGACACGACTGGAGAT

TAAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGC

AG CTG A AGTCTG GCACCGCCAGCGTG GTGTG CCTG CTG A AC AACTTCTACCCC

CGCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAAC

AGCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTG

AGCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACG

CCTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAA

LC-12 hKappa

CCGGGGCGAGTGCTAA (SEQ I D NO: 115)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-13 hlgGl

GATAGTAA (SEQ ID NO: 103)

GATATTGTGATGACTCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGA

GTC ACC ATC ACTTG CCG G G C AAGTC AG G G C ATT AG A AATG ATTT AG G CTG GTA

TCAGCAGAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGATGCCTCCAGTT

TGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATCTGGGACAGATTT

CACTCTCACCATCAGCAGCCTGCAGCCTGAAGA I 1 1 1 GCAACTTATTACTGTCA

ACAGTTTAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAGCTGGAGATCA

LC-13 hKappa

AACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCAG CTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCCG

CGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACAG

CCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGAG

CAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGCC

TGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAACC

GGGGCGAGTGCTAA (SEQ ID NO: 116)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

HC-14 hlgGl

GATAGTAA (SEQ ID NO: 103)

GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAG

AGTCACCATCACTTGCCGGGCCAGTCAGGGCATTAGCAG 1 1 1 1 1 1 AGCCTGGT

ATCAGCAAAAACCAGGGAAAGCCCCTAAGCTCCTGATCTATGATGCATCCACT

TTG C A AAGTG G G GTCCC ATC A AG GTTC AG CG G C AGTGC ATCTG G G AC AG ATT

TC ACTCTC ACC ATC AG C AG CCTG C AG CCTG AAG A 1 1 1 1 GCAACTTATTACTGTC

AACAGCTTAATGGTTACCCTCTCACTTTCGGCGGAGGGACCAAGGTGGAGATC

AAACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCA

GCTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCC

GCGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACA

GCCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGA

GCAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGC

CTGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAAC

LC-14 hKappa

CGGGGCGAGTGCTAA (SEQ ID NO: 117)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AAA AACCTG G CG AA AG C

CTG AAA ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

HC-15 hlgGl

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC

CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

GATAGTAA (SEQ ID NO: 103)

GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGA

GTC ACC ATC ACTTG CCG G G C AAGTC AG G G C ATTG G C AGTG CTTTAGCCTG GTA

TC AG C AG AA ACC AG G GAT AG GTCCTA AG CTCCTG ATCTATG ATG CCTC A ACTT

TGGAAAGTGGGGTCCCAGCAAGGTTCAGCGGCAGTGGATCTAGGACAGATTT

CACTCTCACCATCACCAGCCTGCAGCCTGAAGA I 1 1 1 GCAACTTATTACTGTCA

ACAGTTTAATGGTTACCCTCTCACTTTCGGCGGAGGGACCAAGCTGGAGATCA

AACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCAG

CTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCCG

CGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACAG

CCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGAG

CAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGCC

TGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAACC

LC-15 hKappa

GGGGCGAGTGCTAA (SEQ ID NO: 118)

CAGGTGCAGCTGGTGCAGAGCGGTGCGGCG GTG A AA A AACCTG G CG AA AG C

CTG AA A ATTAG CTG C A A AG G C AG CG G CTATCG 1 1 1 1 ACCACCTATTGGATTGG

CTGGGTGCGTCAGATGCCGGGCAAAGGACTGGAATGGATGGGCATTATCTAT

CCGGGCGATAGCGATACCCGTTACAGCCCTAGCTTTCAGGGGCAGGTGACCA

TTAGCGCGGGAAAAAGCATTAGCACCGCGTATCTGCAGTGGAGCAGCTTAAA

AGCGAGCGACACCGCGATGTATTATTGCGCGCGTCATGGCCGTGGCTATAAT

GGCTATGAAGGCGCGTTTGATATTTGGGGCCAGGGGACTATGGTTACCGTGA

GCAGCGCTAGCACCAAGGGCCCCAGCGTGTTCCCTCTGGCCCCCAGCAGCAA

GAGCACCAGCGGCGGAACCGCCGCCCTGGGCTGCCTGGTGAAGGACTACTTC

CCCGAGCCCGTGACCGTGTCCTGGAACAGCGGCGCTCTGACCAGCGGAGTGC

ACACCTTCCCTGCCGTGCTGCAGAGCAGCGGCCTGTACTCCCTGAGCAGCGTG

GTGACCGTGCCCAGCAGCAGCCTGGGCACCCAGACCTACATCTGCAACGTGA

ACCACAAGCCCTCCAACACCAAGGTGGACAAGAAGGTGGAGCCTAAGAGCTG

CGACAAGACCCACACCTGCCCTCCCTGCCCCGCCCCCGAGCTGCTGGGCGGAC

CCAGCGTGTTCCTGTTCCCTCCCAAGCCCAAGGACACCCTGATGATCAGCCGC

ACCCCCGAGGTGACCTGCGTGGTGGTGGACGTGAGCCACGAGGACCCCGAG

GTGAAGTTCAACTGGTACGTGGACGGCGTGGAGGTGCACAACGCCAAGACCA

AGCCTCGGGAGGAGCAGTACAACTCCACCTACCGCGTGGTGAGCGTGCTGAC

CGTGCTGCACCAGGACTGGCTGAACGGCAAGGAGTACAAGTGCAAGGTGAG

HC-16 hlgGl

CAACAAGGCCCTGCCCGCTCCCATCGAGAAGACCATCAGCAAGGCCAAGGGC CAGCCCCGGGAGCCTCAGGTGTACACCCTGCCCCCCAGCCGCGACGAGCTGA

CCAAGAACCAGGTGAGCCTGACCTGCCTGGTGAAGGGCTTCTACCCCTCCGAC

ATCGCCGTGGAGTGGGAGAGCAACGGCCAGCCTGAGAACAACTACAAGACC

ACCCCTCCCGTGCTGGACAGCGACGGCAGCTTCTTCCTGTACAGCAAGCTGAC

CGTGGACAAGTCCCGGTGGCAGCAGGGCAACGTGTTCAGCTGCAGCGTGATG

CACGAGGCCCTGCACAACCACTACACCCAGAAGAGCCTGAGCCTGAGCCCCG

GATAGTAA (SEQ ID NO: 103)

GCCATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGA

GTC ACC ATC ACTTG CCG G G C AAGTC AG G G C ATT ACC AGTG CTTT AG CCTG GTA

TCAGGAGAAACCAGGGAAAGCTCCTAACCTCCTGATCTATGATGCCTCCAGTT

TGGAAAGTGGGGTCCCATCAAGGTTCAGCGGCAGTGGATATGGGACAGATTT

CACTCTCACCATCAGCAGCCTGCAGCCTGAAGA I 1 1 1 GCAACTTATTACTGTCA

ACAGCTTAATAGTTACCCTCTCACTTTCGGCGGAGGGACCAAAGTGGATATCA

AACGGACCGTGGCCGCCCCCAGCGTGTTCATCTTCCCTCCCAGCGACGAGCAG

CTGAAGTCTGGCACCGCCAGCGTGGTGTGCCTGCTGAACAACTTCTACCCCCG

CGAGGCCAAGGTGCAGTGGAAGGTGGACAACGCCCTGCAGAGCGGCAACAG

CCAGGAGAGCGTGACCGAGCAGGACTCCAAGGACAGCACCTACAGCCTGAG

CAGCACCCTGACCCTGAGCAAGGCCGACTACGAGAAGCACAAGGTGTACGCC

TGCGAGGTGACCCACCAGGGACTGTCTAGCCCCGTGACCAAGAGCTTCAACC

LC-16 hKappa

GGGGCGAGTGCTAA (SEQ ID NO: 119)

cagatccagttggtacagtctggacctgagctgaggaagcctggcgagtcagtgaagatctcctgcaa ggcttctggatataccttcacagactatgcaatgtattgggtgaaacaggctccaggaaagggcttgaa gtggatgggctggatcaacacctatactgggaagccaacatatgctgatgacttcaaaggacgatttgt cttctctttggaagcctctgccaacactgcaaatttgcagatcagcaacctcaaaaatgaggacacggc tacatatttctgtgcaagagcccgcggattagtcgatgactatgttatggatgcctggggtcaagggact

HC-17 hlgGl

tcagtcactgtctcctct (SEQ ID NO: 120)

agctatgagctgatccaaccaccttcggcatcagtcactctgggaaatactgtctcactcacttgtgtcg gagatgaattatcaaaaagatatgctcagtggtatcaacaaaagccagacaagaccattgtgtccgtg atatacaaagatagtgagcggccctcaggcatctctgaccgattctctggttccagctccgggacaaca gccactctgacaatccatggcaccctggctgaggatgaggctgattattactgtttgtcaacatatagtg

LC-17 hLambda

atgataatctccctgttttcggtggtggaaccaagctcactgtccta (SEQ ID NO: 121) gaagtccagctgcagcagtatggggctgagcttgggaaacctgggacctcagtcaggttgtcttgcaa ggtttctggctataacattaggaatacctacattcactgggtgaatcagaggcctggagagggcctgga atggataggaaggattgatcctacaaacggaaatactatatctgctgagaaattcaaaaccaaggcca cactgactgcagatacatcgtcccacacagcctacttgcagttcagccaactgaaatctgacgacaca gcaatctatttttgtgctctgaactatgagggatatgcggattattggggccagggagtcatggtcacag

HC-18 hlgGl

gctcctcc (SEQ ID NO: 122)

gacatccagatgacccagtctccttcattcctgtctgcatctgtgggagacagagtcactatcaactgca aagcaagtcagaatattaacaagtacttaaactggtatcagcaaaaggttggagaagctcccaaacg cctgatatttaagacaaacagtttgcaaacgggcatcccatcaaggttcagtggcagtggatctggaac agattatacactcaccatcagcagcctgcagactgaagatgttgccacatatttctgctttcagtataac

LC-18 hKappa

attgggtacacgtttggagctgggaccaaggtggagctgaaa (SEQ ID NO: 123) gaggtgcagcttcaggagtcaggacctggccttgtgaaaccctcacagtcactctccctcacctgttcg gtcactggatactccatttccagtaattatagatggaactggatccggaagttcccaggaaataaagtg gagtggatgggatatataaacagtgcaggcagtactaactacaatccgtctctcaaaagtcgaatctcc atgactagagacacatccaagaatcagttcttcctgcaggtgaactctgtaacaactgaggacacagc cacttattactgtgcgagatccctaagagggtatattacggattattcaggcttctttgattactggggcc

HC-19 hlgGl

aaggagtcatggtcacagtctcctca (SEQ ID NO: 124)

gatatccggatgacacagtctccagcttccctgtctgcatctctgggagagactgtcaacatcgaatgtc tagcaagtgaggacattttcagtgatttagcatggtatcagcagaagccagggaaatctcctcaactcc tgatctataatgcaaatagcttgcaaaatggggtcccttcacggtttagtggcagtggatctggcacac ggtattctctcaaaataaacagcctgcaatctgaagatgtcgcgacttatttctgtcaacaatataagaa

LC-19 hKappa

ttatccgctcacgttcggttctgggaccaagctggagatcaaa (SEQ ID NO: 125) gaagtccagctgcagcagtatggggctgagcttgggaaacctgggacctcagtcaggttgtcttgcaa gctttctggctataagattaggaatacctacatacactgggtgaatcagaggcctggaaagggcctgg aatggattgggaggattgatcctgcaaatggaaatactatctatgctgagaagttcaaaagcaaggtt acactgactgcagatacatcgtccaacacagcctacatgcaactcagccaactgaaatctgacgacac agcactctatttttgtgctatgaactacgaagggtatgaggattactggggccaaggagtcatggtcac

HC-20 hlgGl

agtctcctca (SEQ ID NO: 126)

gacatccagatgacccagtctccttcattcctgtctgcatctgtgggagacagcgtcactatcaactgca aagcaagtcagaatattaacaagtacttaaattggtatcagcaaaagcttggagaagctcccaaacgc ctgatacataaaacagacagtctgcaaacgggcatcccatcaaggttcagtggcagtggatctggtac agattacacactcaccatcagcagcctgcagcctgaagatgttgccacatacttctgctttcagtataag

LC-20 hKappa

agtgggttcatgtttggagctgggaccaagctggaactgaaa (SEQ ID NO: 127) cagatccagttggtacagtctggacctgagctgaagaagcctggagagtcagtgaagatctcctgcaa ggcctctgggtataccttcacagactatgcagtgtactgggtgatacaggctccaggaaagggcttgaa gtggatgggctggatcaacacctatactgggaagccaacatatgccgatgacttcaaaggacggtttg tcttctctttggaaacctctgccagcactgcaaatttgcagatcagcaacctcaaaaatgaggacacgg ctacatatttctgtgcaagaggagcgggcatgactaaggactatgttatggatgcctggggtcgagggg

HC-21 hlgGl

ttttagtcactgtctcctca (SEQ ID NO: 128)

agctatgagctgatccaaccaccttcggcgtcagtcactctgggaaatactgtctcactcacttgtgtcg gagatgaattatcaaaaagatatgctcagtggtatcaacaaaagccagacaagaccattgtgtccgtg atatacaaagatagtgagcggccctcagacatctctgaccgattctctggttccagctccgggacaaca gccactctgacaatccatggcaccctggctgaggatgaggctgattattactgtttgtcaacatatagtg

LC-21 hLambda

atgataatctccctgttttcggtggtggaaccaagctcactgtccta (SEQ ID NO: 129) caggtgcagctgaaggagtcaggacctggcctggtgcagccctcacagaccctgtctctcacctgcact gtctctggattctcattaaccagctatcttgttcactgggttcgacagcctccaggaaaaactctggagt gggtgggattaatgtggaatgatggagacacatcatataattcagctctcaaatcccgactgagcatca gcagggacacctccaagagccaagttttcttaaagatgcacagtcttcaagctgaggacacagccact tactactgtgccagagagagcaacttgggatttacttactggggccacggcactctggtcactgtctctt

HC-22 hlgGl

ca (SEQ ID NO: 130)

gacatccagatgacacagtctcctgcctccctgtctgcttctctggaagaaattgtcaccatcacctgca aggcaagccagggcattgatgatgacttatcatggtatcagcagaaaccagggaaatctcctcagctc ctgatctatgatgtaaccagattggcagatggggtcccatcacggttcagcggcagtagatctggcaca cagtattctcttaagatcagcagaccacaggttgctgattctggaatctattactgtctgcagagttaca

LC-22 hKappa

gtactccgtacacgtttggagctgggaccaagctggaactgaaa (SEQ ID NO: 131) gaagtccagctgcagcagtatggggctgagcttgggaaacctgggacctcagtcaggttgtcttgcaa ggtttctggctataacattaggaatacctacattcactgggtgcatcagaggcctggagagggcctgga atggataggaaggattgatcctacaaacggaaatactatatctgctgagaagttcaaaagcaaggcc acactgactgcagatacatcgtccaatacagcctacatgcagttcagccaactgaaatctgacgacac agcaatctatttttgtgctatgaactacgaagggtatgcggattattggggccaaggagtcatggtcac

HC-23 hlgGl

agtctcctcc (SEQ ID NO: 132)

gacatccagatgacccagtctccttcattcctgtctgcatctgtgggagacagactcactatcaactgca aagcaagtcagaatattaacaagtacttaaactggtatcagcaaaagcttggagaagctcccaaacg cctgatatttaagacaaacagtttgcaaacgggcatcccatcaaggttcagtggcagtggatctggaac agattacacactcaccatcagcagcctgcagcctgaagatgttgccacatatttctgctttcagtataac

LC-23 hKappa

attgggttcacgtttggagctgggaccaagctggagctgaaa (SEQ ID NO: 133) gaggtgcagctggtggagtctggtggaggcttagtgcagtctggaaggtccctaaaactctcctgtgca gcctcaggattcactgtcagtgactattacatggcctgggtccgccaggctccaacgaaggggctgga gtgggtcgcaaccattaattatgatggtagtaccacttaccatcgagactccgtgaagggccgattcac tatctccagggataatgcaaaaagcaccctatacctgcaaatggacagtctgcggtctgaggacacgg ccacttattactgtgcaagacatggggactatgggtatcactacggggcctattattttgattactgggg

HC-24 hlgGl

ccaaggagtcatggtcacagtctcctca (SEQ ID NO: 134)

gacattgtcttgacccagtctcctgctttggctgtgtctctggggcagagggccactatctcctgtagggc

LC-24 hKappa

cagccagactgtcagtttatctggatataatcttatacactggtaccaacagagaacaggacagcaac ccaaactcctcatctatcgtgcatccaatctagcacctgggatccctgccaggttcagtggcagtgggtc tgggacagacttcaccctcaccatcagccctgtgcagtctgatgatattgcaacctattactgtcagcag agtagggagtcgtggacgttcggtggaggcaccaacttggaaatgaag (SEQ ID NO: 135) cagatccagttggtacagtctggacctgagctgaagaagcctggagagtcagtgaagatctcctgcaa ggcttctgggtataccttcacagactatgcaatacactgggtgaaacaggctccaggacagggcttga ggtggatggcctggatcaacaccgaaactgggaagcctacatatgctgatgacttcaaaggacggttt gtcttctctttggaggcctctgccagcactgcacatttgcagatcagcaacctcaaaaatgaggacacg gctacatttttctgtgcaggcgggtcccattggtttgcttactggggccaaggcactctggtcactgtctc

HC-25 hlgGl

ttca (SEQ ID NO: 136)

agctatgagctgatccaaccaccttcagcatctgtcactctggaaaatactgtctcaatcacttgttctgg agatgaattatcaaacaaatatgctcattggtatcaacaaaagccagacaagaccattttggaagtga tctacaacgatagtgagcggccctcaggcatctctgaccgattctctgggtccagctcagggacaacag ccattctcacaatccgtgatgcccaggctgaggatgaggctgattattactgtttgtcaacatttagtgat

LC-25 hLambda

gatgatctccctattttcggtggtggcaccaagctcactgtccta (SEQ ID NO: 137) cagatccagttggtacagtctggacctgagctgaagaagcctggagagtcagtgaagatctcctgcaa ggcctctgggtataccttcacagactatgcagtgtactgggtgatacaggctccaggaaagggcttgaa gtggatgggctggatcaacacctatactgggaagccaacatatgccgatgacttcaaaggacggtttg tcttctctttggaaacctctgccagcactgcaaatttgcagatcagcaacctcaaaaatgaggacacgg ctacatatttctgtgcaagaggagcgggcatgactaaggactatgttatggatgcctggggtcgagggg

HC-26 hlgGl

ttttagtcactgtctcctca (SEQ ID NO: 128)

agctatgagctgatccaaccaccttcaacatcagtcactctgggaaatactgtctcactcacctgtgttg gaaatgaattaccaaaaagatatgcttattggtttcaacaaaagccagaccagtccattgtgagactg atatatgacgatgacaggcggccctcaggcatctctgaccgattctctgggtccagctctgggacaaca gccactctgacaatccgtgacgcccaggctgaggatgaggcttattattactgtcactcaacatatactg

LC-26 hLambda

atgataaagtccctattttcggtggtggaaccaagctcactgtccta (SEQ ID NO: 138) gaggtgcagctggtggagtctgggggaggcttagtgcagcctggaaggtccatgaaactctcctgtaa ggcctcaggattcactttcagtaactatgacatggcctgggtccgccaggctccaacgaggggtctgga gtgggtcgcatccattagttatgatggtattaccgcttactatcgagactccgtgaagggccgattcact atctccagagagaatgcaaaaagcaccctatacctgcaattggtcagtctgagatctgaggacacggc cacttattactgtacaacagaggggggttatgtgtactccggaccacactactttgattactggggccaa

HC-27 hlgGl

ggagtcatggtcacagtctcctca (SEQ ID NO: 139)

gacattcagatgacccagtctccatcctccatgtctgtgtctctgggagacacagtcactattacttgccg ggcaagtcaggacgttgggatttttgtaaattggttccagcagaaaccagggagatctcctaggcgtat gatttatcgtgcaacgaacttggcagatggggtcccatcaaggttcagcggcagtaggtctggatcaga ttattctctcaccatcagcagcctggagtctgaagatgtggcagactatcactgtctacagtatgatgag

LC-27 hKappa

tttcctcggacgttcggtggaggcaccaagctggaattgaaa (SEQ ID NO: 140) gaagtccagctgcagcagtatggggctgagcttgggaaacctgggacctcagtcaggttgtcttgcaa ggtttctggctataagattaggaatacctacatacactgggtgaatcagaggcctggaaagggcctgg aatggatagggaggattgatcctgcaaatggaaatactatatatgctgagaagttcaaaagcaaggtt acactgactgcagatacatcgtccaacacagcctacatgcaactcagccaactgaaatctgacgacac agcactctatttttgtgctatgaactacgaagggtatgaggattactggggccaaggagtcatggtcac

HC-28 hlgGl

agtctcctca (SEQ ID NO: 141)

gacatccagatgacccagtctccttcattcctgtctgcatctgtgggagacagcgtcactatcaactgca aagcaagtcagaatattaataagtatttaaactggtatcagcaaaagcttggagaagctcccaaacgc ctgatacataaaacaaacagtttgcaaccgggcttcccatcaaggttcagtggcagtggatctggtaca gattacacactcaccatcagcagcctgcagcctgaagatgttgccgcatatttctgctttcagtataaca

LC-28 hKappa

gtgggttcacgtttggagctgggaccaagctggaactgaaa (SEQ ID NO: 142)

As described below, an scFV phage display library screen of human antibodies was

performed to identify novel anti-CD1 17 antibodies, and fragments thereof, having therapeutic use. Antibodies 85 (Ab85), 86 (Ab86), 87 (Ab87), 88 (Ab88), and 89 (Ab89), among others, were identified in this screen.

The heavy chain variable region (VH) amino acid sequence of Ab85 is provided below as SEQ ID NO: 143. The VH CDR amino acid sequences of Ab85 are underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IINPRDSDTRYRPSFQG (VH CDR2; SEQ ID NO: 146); and HGRGYEGYEGAFDI (VH CDR3; SEQ ID NO: 147).

Ab85 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMAIINPRDSDTRYRPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGRGYEGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 143)

The light chain variable region (VL) amino acid sequence of Ab85 is provided below as SEQ ID NO 144. The VL CDR amino acid sequences of Ab85 are underlined below and are as follows: RSSQGIRSDLG (VL CDR1 ; SEQ ID NO: 148); DASNLET (VL CDR2; SEQ ID NO: 149); and QQANGFPLT (VL CDR3; SEQ ID NO: 150).

Ab85 VL sequence

DIQMTQSPSSLSASVGDRVTITCRSSQGIRSDLGWYQQKPGKAPKLLIYDASNLETGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIK (SEQ ID NO: 144)

Antibody HC-86/LC-86 (Ab86)

The heavy chain variable region (VH) amino acid sequence of Ab86 is provided below as SEQ ID NO: 151 . The VH CDR amino acid sequences Ab86 are underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IIYPGDSDIRYSPSLQG (VH CDR2; SEQ ID NO: 153); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab86 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSDIRYSPSL QGQVTISVDTSTSTAYLQWNSLKPSDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 151 )

The light chain variable region (VL) amino acid sequence of Ab86 is provided below as SEQ ID NO 152. The VL CDR amino acid sequences of Ab86 are underlined below and are as follows: RASQGIGDSLA (VL CDR1 ; SEQ ID NO: 154); DASNLET (VL CDR2; SEQ ID NO: 149); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab86 VL sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIGDSLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGS

GSGTDFTLTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID NO: 152) Antibody HC-87/LC-87 (Ab87)

The heavy chain variable region (VH) amino acid sequence of Ab87 is provided below as SEQ ID NO: 143. The VH CDR amino acid sequences of Ab87 are underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IINPRDSDTRYRPSFQG (VH CDR2; SEQ ID NO: 146); and HGRGYEGYEGAFDI (VH CDR3; SEQ ID NO: 147).

Ab87 VH sequence

The light chain variable region (VL) amino acid sequence of Ab87 is provided below as SEQ ID NO 156. The VL CDR amino acid sequences of Ab87 are underlined below and are as follows: RASQGIRNDLG (VL CDR1 ; SEQ ID NO: 157); DASSLES (VL CDR2; SEQ ID NO: 5); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab87 VL sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYDASSLESGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID NO: 156)

Antibody HC-88/LC-88 (Ab88)

The heavy chain variable region (VH) amino acid sequence of Ab88 is provided below as SEQ ID NO: 158. The VH CDR amino acid sequences of Ab88 are underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IIYPGDSLTRYSPSFQG (VH CDR2; SEQ ID NO: 159); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab88 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSLTRYSPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 158)

The light chain variable region (VL) amino acid sequence of Ab88 is provided below as SEQ ID NO: 156. The VL CDR amino acid sequences of Ab88 are underlined below and are as follows: RASQGIRNDLG (VL CDR1 ; SEQ ID NO: 157); DASSLES (VL CDR2; SEQ ID NO: 5); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab88 VL sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQKPGKAPKLLIYDASSLESGVPSRFSGS

GSGTDFTLTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID NO: 156) Antibody HC-89/LC-89 (Ab89)

The heavy chain variable region (VH) amino acid sequence of Ab89 is provided below as SEQ ID NO: 160. The VH CDR amino acid sequences of Ab89 are underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IIYPGDSDTRYSPSFQG (VH CDR2; SEQ ID NO: 2); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab89 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 160)

The light chain variable region (VL) amino acid sequence of Ab89 is provided below as SEQ ID NO: 152. The VL CDR amino acid sequences of Ab89 are underlined below and are as follows: RASQGIGDSLA (VL CDR1 ; SEQ ID NO: 154); DASNLET (VL CDR2; SEQ ID NO: 149); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab89 VL sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIGDSLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID NO: 152)

Antibody HC-249/LC-249 (Ab249)

The heavy chain variable region (VH) amino acid sequence of Ab249 is provided below as SEQ ID NO: 98. The VH CDR amino acid sequences of Ab249 are underlined below and are as follows: TSWIG (VH CDR1 ; SEQ ID NO: 186); IIYPGDSDTRYSPSFQG (VH CDR2; SEQ ID NO: 2); and HGLGYNGYEGAFDI (VH CDR3; SEQ ID NO: 187).

Ab249 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 98)

The light chain variable region (VL) amino acid sequence of Ab249 is provided below as SEQ ID NO: 102. The VL CDR amino acid sequences of Ab249 are underlined below and are as follows: RASQGIGSALA (VL CDR1 ; SEQ ID NO: 188); DASNLET (VL CDR2; SEQ ID NO: 149); and QQLNGYPLT (VL CDR3; SEQ ID NO: 189).

Ab249 VL sequence DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQKPGKAPKLLIYDASNLETGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQLNGYPLTFGQGTRLEIK (SEQ ID NO: 102)

Human antibodies Ab85 and Ab249 were both derived from antibody CK6, which is an antagonist anti-CD1 17 antibody. A comparison of the amino acid sequences of the variable regions of Ab85 and Ab249 versus CK6 is shown in Figures 5A to 5D. Both antibodies have improved properties over CK6.

CK6 includes a potential deamidation site in the CDR3 domain of the heavy chain variable region. While advantageous to remove for future production of the antibody, the position of the asparagine presents a significant challenge. The potential deamidation site was successfully removed, however, in the Ab85 heavy chain CDR3 such that the antibody (having Ab85 heavy and light chain CDRs) was able to maintain a high affinity level specificity for human CD1 17 and the ability to internalize. Further, Ab85 has an improved off rate (i.e., slower off rate) relative to its parent.

Thus, in certain embodiments, an anti-CD1 17 antibody comprises a heavy chain comprising a CDR set (CDR1 , CDR2, and CDR3) as set forth in SEQ ID Nos: 145, 146, and 147, and a light chain comprising a CDR set as set forth in SEQ ID Nos: 148, 149, and 150, internalizes in cells expressing CD1 17, and has a k_off (i.e., k_dis) rate of 5 x 10^~4 s^"1 or less as measured by BLI.

As described in Jain et al. (2017) PNAS 1 14 (5) 944-949, while the activity of an antibody is key for developing it as a therapeutic, what is often overlooked is the "developability" of an antibody for manufacturing. Identifying an antibody that can achieve both therapeutic and superior biophysical characteristics is challenging. Indeed, biophysical properties of an antibody are essential for antibodies being used for therapeutic purposes. Biophysical testing of Ab 85 indicated that it is a particularly stable antibody. For example, a population of Ab85 antibodies maintains a low level of acid variants even at higher temperatures over time (see Figure 7A and 7B). This was true even in relation to other CK6-derived antibodies. Thus, in certain

embodiments, included in the invention is a composition comprising less than 20% acidic variants as determined by capillary electrophoresis following storage at 25 degrees Celsius for seven days, wherein the antibody is an IgG antibody that specifically binds to CD1 17 and comprises a heavy chain comprising a CDR set (CDR1 , CDR2, and CDR3) as set forth in SEQ ID Nos: 145, 146, and 147, and a light chain comprising a CDR set as set forth in SEQ ID Nos: 148, 149, and 150.

The anti-CD1 17 antibodies or binding fragments described herein may also include modifications and/or mutations that alter the properties of the antibodies and/or fragments, such as those that increase half-life, increase or decrease ADCC, etc., as is known in the art.

In one embodiment, the anti-CD1 17 antibody, or binding fragment thereof, comprises a variant Fc region, wherein said variant Fc region comprises at least one amino acid modification relative to a wild-type Fc region, such that said molecule has an altered affinity for an FcgammaR.

Certain amino acid positions within the Fc region are known through crystallography studies to make a direct contact with FcvR. Specifically amino acids 234-239 (hinge region), amino acids 265-269 (B/C loop), amino acids 297-299 (C'/E loop), and amino acids 327-332 (F/G) loop, (see Sondermann et al., 2000 Nature, 406: 267-273). For example, amino acid substitutions at amino acid positions 234 and 235 of the Fc region have been identified as decreasing affinity of an IgG antibody for binding to an Fc receptor, particularly an Fc gamma receptor (FcvR). In one embodiment, an anti-CD1 17 antibody described herein comprises an Fc region comprising an amino acid substitution at L234 and/or L235, e.g., L234A and L235A (EU index). Thus, the anti- CD1 17 antibodies described herein may comprise variant Fc regions comprising modification of at least one residue that makes a direct contact with an FcvR based on structural and

crystallographic analysis. In one embodiment, the Fc region of the anti-CD1 17 antibody (or Fc containing fragment thereof) comprises an amino acid substitution at amino acid 265 according to the EU index as in Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, NH1 , MD (1991 ), expressly incorporated herein by references. The "EU index as in Kabat" or "EU index" refers to the numbering of the human lgG1 EU antibody and is used herein in reference to Fc amino acid positions unless otherwise indicated.

In one embodiment, the Fc region comprises a D265A mutation. In one embodiment, the Fc region comprises a D265C mutation.

In one embodiment, an anti-CD1 17 antibody described herein comprises an Fc region comprising L235A, L235A, and D265C (EU index). The antibodies of the invention may be further engineered to further modulate antibody half-life by introducing additional Fc mutations, such as those described for example in (Dall'Acqua et al. (2006) J Biol Chem 281 : 23514-24), (Zalevsky et al. (2010) Nat Biotechnol 28: 157-9), (Hinton et al. (2004) J Biol Chem 279: 6213-6), (Hinton et al. (2006) J Immunol 176: 346-56), (Shields et al. (2001 ) J Biol Chem 276: 6591 -604), (Petkova et al. (2006) Int Immunol 18: 1759-69), (Datta-Mannan et al. (2007) Drug Metab Dispos 35: 86-94), (Vaccaro et al. (2005) Nat Biotechnol 23: 1283-8), (Yeung et al. (2010) Cancer Res 70: 3269-77) and (Kim et al. (1999) Eur J Immunol 29: 2819-25), and include positions 250, 252, 253, 254, 256, 257, 307, 376, 380, 428, 434 and 435. Exemplary mutations that may be made singularly or in combination are T250Q, M252Y, 1253A, S254T, T256E, P2571 , T307A, D376V, E380A, M428L, H433K, N434S, N434A, N434H, N434F, H435A and H435R mutations.

Thus, in one embodiment, the Fc region comprises a mutation resulting in a decrease in half life. An antibody having a short half life may be advantageous in certain instances where the antibody is expected to function as a short-lived therapeutic, e.g., the conditioning step described herein where the antibody is administered followed by HSCs. Ideally, the antibody would be substantially cleared prior to delivery of the HSCs, which also generally express CD1 17 but are not the target of the anti-CD1 17 antibody, unlike the endogenous stem cells. In one embodiment, the Fc region comprises a mutation at position 435 (EU index according to Kabat). In one

embodiment, the mutation is an H435A mutation. In one embodiment, the anti-CD1 17 antibody described herein has a half life of equal to or less than 24 hours, equal to or less than 22 hours, equal to or less than 20 hours, equal to or less than 18 hours, equal to or less than 16 hours, equal to or less than 14 hours, equal to or less than 13 hours, equal to or less than 12 hours, or equal to or less than 1 1 hours. In another

embodiment, the anti-CD1 17 antibody described herein has a half life between about 22 and 24 hours, between about 20 and 22 hours, between about 18 and 20 hours, between about 16 and 18 hours, between about 14 and 16 hours, between about 12 and 14 hours, between about 10 and 12 hours, or between about 8 and 10 hours.

Anti-CD1 17 antibodies that can be used in conjunction with the patient conditioning methods described herein include, for instance, antibodies produced and released from ATCC Accession No. 10716 (deposited as BA7.3C.9), such as the SR-1 antibody, which is described, for example, in US Patent No. 5,489,516, the disclosure of which is incorporated herein by reference as it pertains to anti-CD1 17 antibodies.

In one embodiment, an anti-CD1 17 antibody described herein comprises an Fc region comprising L235A, L235A, D265C, and H435A (EU index).

Additional anti-CD1 17 antibodies that can be used in conjunction with the patient conditioning methods described herein include those described in US Patent No. 7,915,391 , which describes, e.g., humanized SR-1 antibodies; US Patent No. 5,808,002, which describes, e.g., the anti-CD1 17 A3C6E2 antibody, as well as those described in, for example, WO 2015/050959, which describes anti-CD1 17 antibodies that bind epitopes containing Pro317, Asn320, Glu329, Val331 , Asp332, Lus358, Glue360, Glue376, His378, and/or Thr380 of human CD1 17; and US 2012/0288506 (also published as US Patent No. 8,552,157), which describes, e.g., the anti-CD1 17 antibody CK6, having the CDR sequences of:

a CDR-H1 having the amino acid sequence SYWIG (SEQ ID NO: 1 );

a CDR-H2 having the amino acid sequence IIYPGDSDTRYSPSFQG (SEQ ID NO: 2);

a CDR-H3 having the amino acid sequence HGRGYNGYEGAFDI (SEQ ID NO: 3);

a CDR-L1 having the amino acid sequence RASQGISSALA (SEQ ID NO: 4);

a CDR-L2 having the amino acid sequence DASSLES (SEQ ID NO: 5); and

a CDR-L3 having the amino acid sequence CQQFNSYPLT (SEQ ID NO: 6)

The heavy chain variable region amino acid sequence of CK6 is provided in SEQ ID

NO: 161 ):

QVQLVQSGAAVKKPGESLKISCKGSGYRFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTI SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID NO: 161 ; CDRs are underlined are in bold).

The light chain amino acid variable sequence of CK6 is provided in SEQ ID NO: 162: AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQQKPGKAPKLLIYDASSLESGVPSRFSGS GSGTD FTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK (SEQ ID NO: 162; CDRs are underlined and in bold). Additional anti-CD1 17 antibodies and antigen-binding fragments thereof that may be used in conjunction with the compositions and methods described herein include those described in US 2015/0320880, such as the clones 9P3, NEG024, NEG027, NEG085, NEG086, and 20376.

The disclosures of each of the foregoing publications are incorporated herein by reference as they pertain to anti-CD1 17 antibodies. Antibodies and antigen-binding fragments that may be used in conjunction with the compositions and methods described herein include the above- described antibodies and antigen-binding fragments thereof, as well as humanized variants of those non-human antibodies and antigen-binding fragments described above and antibodies or antigen-binding fragments that bind the same epitope as those described above, as assessed, for instance, by way of a competitive CD1 17 binding assay.

Exemplary antigen-binding fragments of the foregoing antibodies include a dual-variable immunoglobulin domain, a single-chain Fv molecule (scFv), a diabody, a triabody, a nanobody, an antibody-like protein scaffold, a Fv fragment, a Fab fragment, a F(ab')₂ molecule, and a tandem di- scFv, among others.

Antibodies may be produced using recombinant methods and compositions, e.g., as described in U.S. Pat. No. 4,816,567. In one embodiment, isolated nucleic acid encoding an anti- CD1 17 antibody described herein is provided. Such nucleic acid may encode an amino acid sequence comprising the VL and/or an amino acid sequence comprising the VH of the antibody (e.g., the light and/or heavy chains of the antibody). In a further embodiment, one or more vectors (e.g., expression vectors) comprising such nucleic acid are provided. In a further embodiment, a host cell comprising such nucleic acid is provided. In one such embodiment, a host cell comprises (e.g., has been transformed with): (1 ) a vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and an amino acid sequence comprising the VH of the antibody, or (2) a first vector comprising a nucleic acid that encodes an amino acid sequence comprising the VL of the antibody and a second vector comprising a nucleic acid that encodes an amino acid sequence comprising the VH of the antibody. In one embodiment, the host cell is eukaryotic, e.g. a Chinese Hamster Ovary (CHO) cell or lymphoid cell (e.g., Y0, NS0, Sp20 cell). In one embodiment, a method of making an anti-CLL-1 antibody is provided, wherein the method comprises culturing a host cell comprising a nucleic acid encoding the antibody, as provided above, under conditions suitable for expression of the antibody, and optionally recovering the antibody from the host cell (or host cell culture medium).

For recombinant production of an anti-CD1 17 antibody, nucleic acid encoding an antibody, e.g., as described above, is isolated and inserted into one or more vectors for further cloning and/or expression in a host cell. Such nucleic acid may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the antibody).

Suitable host cells for cloning or expression of antibody-encoding vectors include prokaryotic or eukaryotic cells described herein. For example, antibodies may be produced in bacteria, in particular when glycosylation and Fc effector function are not needed. For expression of antibody fragments and polypeptides in bacteria, see, e.g., U.S. Pat. Nos. 5,648,237, 5,789,199, and 5,840,523. (See also Charlton, Methods in Molecular Biology, Vol. 248 (B.K.C. Lo, ed., Humana Press, Totowa, N.J., 2003), pp. 245-254, describing expression of antibody fragments in E. coli.) After expression, the antibody may be isolated from the bacterial cell paste in a soluble fraction and can be further purified.

Vertebrate cells may also be used as hosts. For example, mammalian cell lines that are adapted to grow in suspension may be useful. Other examples of useful mammalian host cell lines are monkey kidney CV1 line transformed by SV40 (COS-7); human embryonic kidney line (293 or 293 cells as described, e.g., in Graham et al., J. Gen Virol. 36:59 (1977)); baby hamster kidney cells (BHK); mouse Sertoli cells (TM4 cells as described, e.g., in Mather, Biol. Reprod. 23:243-251 (1980)); monkey kidney cells (CV1 ); African green monkey kidney cells (VERO-76); human cervical carcinoma cells (HELA); canine kidney cells (MDCK; buffalo rat liver cells (BRL 3A);

human lung cells (W138); human liver cells (Hep G2); mouse mammary tumor (MMT 060562); TRI cells, as described, e.g., in Mather et al., Annals N.Y. Acad. Sci. 383:44-68 (1982); MRC 5 cells; and FS4 cells. Other useful mammalian host cell lines include Chinese hamster ovary (CHO) cells, including DHFR- CHO cells (Urlaub et al., Proc. Natl. Acad. Sci. USA 77:4216 (1980)); and myeloma cell lines such as Y0, NS0 and Sp2/0. For a review of certain mammalian host cell lines suitable for antibody production, see, e.g., Yazaki and Wu, Methods in Molecular Biology, Vol. 248 (B. K. C. Lo, ed., Humana Press, Totowa, N.J.), pp. 255-268 (2003).

In one embodiment, the anti-CD1 17 antibody, or antigen binding fragment thereof, comprises variable regions having an amino acid sequence that is at least 95%, 96%, 97% or 99% identical to the SEQ ID Nos disclosed herein. Alternatively, the anti-CD1 17 antibody, or antigen binding fragment thereof, comprises CDRs comprising the SEQ ID Nos disclosed herein with framework regions of the variable regions described herein having an amino acid sequence that is at least 95%, 96%, 97% or 99% identical to the SEQ ID Nos disclosed herein.

In one embodiment, the anti-CD1 17 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region and a heavy chain constant region having an amino acid sequence that is disclosed herein. In another embodiment, the anti-CD1 17 antibody, or antigen binding fragment thereof, comprises a light chain variable region and a light chain constant region having an amino acid sequence that is disclosed herein. In yet another embodiment, the anti- CD1 17 antibody, or antigen binding fragment thereof, comprises a heavy chain variable region, a light chain variable region, a heavy chain constant region and a light chain constant region having an amino acid sequence that is disclosed herein.

Methods of Identifying Anti-CD117 Antibodies

Methods for high throughput screening of antibody, or antibody fragment, libraries for molecules capable of binding CD1 17 (e.g., GNNK+ CD1 17) can be used to identify and affinity mature antibodies useful for treating cancers, autoimmune diseases, and conditioning a patient (e.g., a human patient) in need of hematopoietic stem cell therapy as described herein. Such methods include in vitro display techniques known in the art, such as phage display, bacterial display, yeast display, mammalian cell display, ribosome display, mRNA display, and cDNA display, among others. The use of phage display to isolate ligands that bind biologically relevant molecules has been reviewed, for example, in Felici et al., Biotechnol. Annual Rev. 1 :149-183, 1995; Katz, Annual Rev. Biophys. Biomol. Struct. 26:27-45, 1997; and Hoogenboom et al., Immunotechnology 4:1 -20, 1998, the disclosures of each of which are incorporated herein by reference as they pertain to in vitro display techniques. Randomized combinatorial peptide libraries have been constructed to select for polypeptides that bind cell surface antigens as described in Kay, Perspect. Drug Discovery Des. 2:251 -268, 1995 and Kay et al., Mol. Divers. 1 :139-140, 1996, the disclosures of each of which are incorporated herein by reference as they pertain to the discovery of antigen-binding molecules. Proteins, such as multimeric proteins, have been successfully phage-displayed as functional molecules (see, for example, EP 0349578; EP 4527839; and EP 0589877, as well as Chiswell and McCafferty, Trends Biotechnol. 10:80-84 1992, the disclosures of each of which are incorporated herein by reference as they pertain to the use of in vitro display techniques for the discovery of antigen-binding molecules). In addition, functional antibody fragments, such as Fab and scFv fragments, have been expressed in in vitro display formats (see, for example, McCafferty et al., Nature 348:552- 554, 1990; Barbas et al., Proc. Natl. Acad. Sci. USA 88:7978-7982, 1991 ; and Clackson et al., Nature 352:624-628, 1991 , the disclosures of each of which are incorporated herein by reference as they pertain to in vitro display platforms for the discovery of antigen-binding molecules). These techniques, among others, can be used to identify and improve the affinity of antibodies that bind CD1 17 (e.g., GNNK+ CD1 17) that can in turn be used to deplete endogenous hematopoietic stem cells in a patient (e.g., a human patient) in need of hematopoietic stem cell transplant therapy.

In addition to in vitro display techniques, computational modeling techniques can be used to design and identify antibodies, or antibody fragments, in silico that bind CD1 17 (e.g., GNNK+ CD1 17). For example, using computational modeling techniques, one of skill in the art can screen libraries of antibodies, or antibody fragments, in silico for molecules capable of binding specific epitopes, such as extracellular epitopes of this antigen. The antibodies, or antigen-binding fragments thereof, identified by these computational techniques can be used in conjunction with the therapeutic methods described herein, such as the cancer and autoimmune disease treatment methods described herein and the patient conditioning procedures described herein.

Additional techniques can be used to identify antibodies, or antigen-binding fragments thereof, that bind CD1 17 (e.g., GNNK+ CD1 17) on the surface of a cell (e.g., a cancer cell, autoimmune cell, or hematopoietic stem cell) and that are internalized by the cell, for instance, by receptor-mediated endocytosis. For example, the in vitro display techniques described above can be adapted to screen for antibodies, or antigen-binding fragments thereof, that bind CD1 17 (e.g., GNNK+ CD1 17) on the surface of a cancer cell, autoimmune cell, or hematopoietic stem cell and that are subsequently internalized. Phage display represents one such technique that can be used in conjunction with this screening paradigm. To identify antibodies, or fragments thereof, that bind CD1 17 (e.g., GNNK+ CD1 17) and are subsequently internalized by cancer cells, autoimmune cells, or hematopoietic stem cells, one of skill in the art can adapt the phage display techniques described, for example, in Williams et al., Leukemia 19:1432-1438, 2005, the disclosure of which is incorporated herein by reference in its entirety. For example, using mutagenesis methods known in the art, recombinant phage libraries can be produced that encode antibodies, antibody fragments, such as scFv fragments, Fab fragments, diabodies, triabodies, and ¹⁰Fn3 domains, among others, that contain randomized amino acid cassettes (e.g., in one or more, or all, of the CDRs or equivalent regions thereof or an antibody or antibody fragment). The framework regions, hinge, Fc domain, and other regions of the antibodies or antibody fragments may be designed such that they are non-immunogenic in humans, for instance, by virtue of having human germline antibody sequences or sequences that exhibit only minor variations relative to human germline antibodies.

Using phage display techniques described herein or known in the art, phage libraries containing randomized antibodies, or antibody fragments, covalently bound to the phage particles can be incubated with CD1 17 (e.g., GNNK+ CD1 17) antigen, for instance, by first incubating the phage library with blocking agents (such as, for instance, milk protein, bovine serum albumin, and/or IgG so as to remove phage encoding antibodies, or fragments thereof, that exhibit nonspecific protein binding and phage that encode antibodies or fragments thereof that bind Fc domains, and then incubating the phage library with a population of hematopoietic stem cells. The phage library can be incubated with the target cells, such as cancer cells, autoimmune cells, or hematopoietic stem cells for a time sufficient to allow CD1 17-specific antibodies, or antigen- binding fragments thereof, (e.g., GNNK+ CD1 17-specific antibodies, or antigen-binding fragments thereof) to bind cell-surface CD1 17 (e.g., sell-surface GNNK+ CD1 17) antigen and to

subsequently be internalized by the cancer cells, autoimmune cells, or hematopoietic stem cells (e.g., from 30 minutes to 6 hours at 4° C, such as 1 hour at 4° C). Phage containing antibodies, or fragments thereof, that do not exhibit sufficient affinity for one or more of these antigens so as to permit binding to, and internalization by, cancer cells, autoimmune cells, or hematopoietic stem cells can subsequently be removed by washing the cells, for instance, with cold (4° C) 0.1 M glycine buffer at pH 2.8. Phage bound to antibodies, or fragments thereof, or that have been internalized by the cancer cells, autoimmune cells, or hematopoietic stem cells can be identified, for instance, by lysing the cells and recovering internalized phage from the cell culture medium. The phage can then be amplified in bacterial cells, for example, by incubating bacterial cells with recovered phage in 2xYT medium using methods known in the art. Phage recovered from this medium can then be characterized, for instance, by determining the nucleic acid sequence of the gene(s) encoding the antibodies, or fragments thereof, inserted within the phage genome. The encoded antibodies, or fragments thereof, or can subsequently be prepared de novo by chemical synthesis (for instance, of antibody fragments, such as scFv fragments) or by recombinant expression (for instance, of full-length antibodies).

The internalizing capacity of the prepared antibodies, or fragments thereof, can be assessed, for instance, using radionuclide internalization assays known in the art. For example, antibodies, or fragments thereof, identified using in vitro display techniques described herein or known in the art car be functionalized by incorporation of a radioactive isotope, such as ¹⁸F, ⁷⁵Br, ⁷⁷Br, ¹²²l, ¹²³l, ¹²⁴l, ¹²⁵l, ¹²⁹l ¹³¹ l, ²¹¹At, ⁶⁷Ga, ¹¹¹ ln, "Tc, ¹⁶⁹Yb, ¹⁸⁶Re, ⁶⁴Cu, ⁶⁷Cu, ¹⁷⁷Lu, ⁷⁷As, ⁷²As, ⁸⁶Y, ⁹⁰Y, ⁸⁹Zr, ²¹²Bi, ²¹³Bi, or ²²⁵ Ac For instance, radioactive halogens, such as ¹⁸F, ⁷⁵Br, ⁷⁷Br, ¹²²l, ¹²³l, ¹²⁴l, ¹²⁵l, ¹²⁹l, ¹³¹1, ²¹¹ At, can be incorporated into antibodies, or fragments thereof, using beads, such as polystyrene beads, containin electrophilic halogen reagents (e.g., lodination Beads, Thermo Fisher Scientific, Inc., Cambridge, MA Radiolabeled antibodies, or fragments thereof, can be incubated with cancer cells, autoimmune cells, or hematopoietic stem cells for a time sufficient to permit internalization (e.g., from 30 minutes to 6 hours at 4° C, such as 1 hour at 4° C). The cells can then be washed to remove non-internalized antibodies, or fragments thereof, (e.g., using cold (4° C) 0.1 M glycine buffer at pH 2.8). Internalized antibodies, or fragments thereof, can be identified by detecting the emitted radiation (e.g., γ-radiation) of the resulting cancer cells, autoimmune cells, or hematopoietic stem cells in comparison with the emitted radiation (e.g., γ-radiation) of the recovered wash buffer.

Methods of Treatment

As described herein, hematopoietic stem cell transplant therapy can be administered to a subject in need of treatment so as to populate or re-populate one or more blood cell types.

Hematopoietic stem cells generally exhibit multi-potency, and can thus differentiate into multiple different blood lineages including, but not limited to, granulocytes (e.g., promyelocytes,

neutrophils, eosinophils, basophils), erythrocytes (e.g., reticulocytes, erythrocytes), thrombocytes (e.g., megakaryoblasts, platelet producing megakaryocytes, platelets), monocytes (e.g.,

monocytes, macrophages), dendritic cells, microglia, osteoclasts, and lymphocytes (e.g., NK cells, B-cells and T-cells). Hematopoietic stem cells are additionally capable of self-renewal, and can thus give rise to daughter cells that have equivalent potential as the mother cell, and also feature the capacity to be reintroduced into a transplant recipient whereupon they home to the

hematopoietic stem cell niche and re-establish productive and sustained hematopoiesis.

Hematopoietic stem cells can thus be administered to a patient defective or deficient in one or more cell types of the hematopoietic lineage in order to re-constitute the defective or deficient population of cells in vivo, thereby treating the pathology associated with the defect or depletion in the endogenous blood cell population. The compositions and methods described herein can thus be used to treat a non-malignant hemoglobinopathy (e.g., a hemoglobinopathy selected from the group consisting of sickle cell anemia, thalassemia, Fanconi anemia, aplastic anemia, and

Wiskott-Aldrich syndrome). Additionally or alternatively, the compositions and methods described herein can be used to treat an immunodeficiency, such as a congenital immunodeficiency.

Additionally or alternatively, the compositions and methods described herein can be used to treat an acquired immunodeficiency (e.g., an acquired immunodeficiency selected from the group consisting of HIV and AIDS). The compositions and methods described herein can be used to treat a metabolic disorder (e.g., a metabolic disorder selected from the group consisting of glycogen storage diseases, mucopolysaccharidoses, Gaucher's Disease, Hurlers Disease, sphingolipidoses, and metachromatic leukodystrophy).

Additionally or alternatively, the compositions and methods described herein can be used to treat a malignancy or proliferative disorder, such as a hematologic cancer, myeloproliferative disease. In the case of cancer treatment, the compositions and methods described herein may be administered to a patient so as to deplete a population of endogenous hematopoietic stem cells prior to hematopoietic stem cell transplantation therapy, in which case the transplanted cells can home to a niche created by the endogenous cell depletion step and establish productive hematopoiesis. This, in turn, can re-constitute a population of cells depleted during cancer cell eradication, such as during systemic chemotherapy. Exemplary hematological cancers that can be treated using the compositions and methods described herein include, without limitation, acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma, diffuse large B-cell lymphoma, and non-Hodgkin's lymphoma, as well as other cancerous conditions, including neuroblastoma.

Additional diseases that can be treated with the compositions and methods described herein include, without limitation, adenosine deaminase deficiency and severe combined immunodeficiency, hyper immunoglobulin M syndrome, Chediak-Higashi disease, hereditary lymphohistiocytosis, osteopetrosis, osteogenesis imperfecta, storage diseases, thalassemia major, systemic sclerosis, systemic lupus erythematosus, multiple sclerosis, and juvenile rheumatoid arthritis.

The antibodies, or antigen-binding fragments thereof, described herein may be used to induce solid organ transplant tolerance. For instance, the compositions and methods described herein may be used to deplete or ablate a population of cells from a target tissue (e.g., to deplete hematopoietic stem cells from the bone marrow stem cell niche). Following such depletion of cells from the target tissues, a population of stem or progenitor cells from an organ donor (e.g., hematopoietic stem cells from the organ donor) may be administered to the transplant recipient, and following the engraftment of such stem or progenitor cells, a temporary or stable mixed chimerism may be achieved, thereby enabling long-term transplant organ tolerance without the need for further immunosuppressive agents. For example, the compositions and methods described herein may be used to induce transplant tolerance in a solid organ transplant recipient (e.g., a kidney transplant, lung transplant, liver transplant, and heart transplant, among others). The compositions and methods described herein are well-suited for use in connection the induction of solid organ transplant tolerance, for instance, because a low percentage temporary or stable donor engraftment is sufficient to induce long-term tolerance of the transplanted organ.

In addition, the compositions and methods described herein can be used to treat cancers directly, such as cancers characterized by cells that are CD1 17+. For instance, the compositions and methods described herein can be used to treat leukemia, particularly in patients that exhibit CD1 17+ leukemic cells. By depleting CD1 17+ cancerous cells, such as leukemic cells, the compositions and methods described herein can be used to treat various cancers directly.

Exemplary cancers that may be treated in this fashion include hematological cancers, such as acute myeloid leukemia, acute lymphoid leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, multiple myeloma, diffuse large B-cell lymphoma, and non-Hodgkin's lymphoma.

Acute myeloid leukemia (AML) is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that build up in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute leukemia affecting adults, and its incidence increases with age. The symptoms of AML are caused by replacement of normal bone marrow with leukemic cells, which causes a drop in red blood cells, platelets, and normal white blood cells. As an acute leukemia, AML progresses rapidly and may be fatal within weeks or months if left untreated. In one embodiment, the anti-CD1 17 antibodies described herein are used to treat AML in a human patient in need thereof. In certain embodiments the anti-CD1 17 antibody treatment depletes AML cells in the treated subjects. In some embodiments 50% or more of the AML cells are depleted. In other embodiments, 60% or more of the AML cells are depleted, or 70% or more of the AML cells are depleted, or 80% of more or 90% or more, or 95% or more of the AML cells are depleted. In certain embodiments the anti-CD1 17 antibody treatments is a single dose treatment. In certain embodiments the single dose of anti-CD1 17 antibody treatment depletes 60%, 70%, 80%, 90% or 95% or more of the AML cells.

In addition, the compositions and methods described herein can be used to treat autoimmune disorders. For instance, an antibody, or antigen-binding fragment thereof, can be administered to a subject, such as a human patient suffering from an autoimmune disorder, so as to kill a CD1 17+ immune cell. The CD1 17+ immune cell may be an autoreactive lymphocyte, such as a T-cell that expresses a T-cell receptor that specifically binds, and mounts an immune response against, a self antigen. By depleting self-reactive, CD1 17+ cells, the compositions and methods described herein can be used to treat autoimmune pathologies, such as those described below. Additionally or alternatively, the compositions and methods described herein can be used to treat an autoimmune disease by depleting a population of endogenous hematopoietic stem cells prior to hematopoietic stem cell transplantation therapy, in which case the transplanted cells can home to a niche created by the endogenous cell depletion step and establish productive hematopoiesis. This, in turn, can re-constitute a population of cells depleted during autoimmune cell eradication. Autoimmune diseases that can be treated using the compositions and methods described herein include, without limitation, psoriasis, psoriatic arthritis, Type 1 diabetes mellitus (Type 1 diabetes), rheumatoid arthritis (RA), human systemic lupus (SLE), multiple sclerosis (MS), inflammatory bowel disease (IBD), lymphocytic colitis, acute disseminated encephalomyelitis (ADEM), Addison's disease, alopecia universalis, ankylosing spondylitisis, antiphospholipid antibody syndrome (APS), aplastic anemia, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune inner ear disease (AIED), autoimmune lymphoproliferative syndrome (ALPS), autoimmune oophoritis, Balo disease, Behcet's disease, bullous pemphigoid, cardiomyopathy, Chagas' disease, chronic fatigue immune dysfunction syndrome (CFIDS), chronic inflammatory demyelinating polyneuropathy, Crohn's disease, cicatrical pemphigoid, coeliac sprue-dermatitis herpetiformis, cold agglutinin disease, CREST syndrome, Degos disease, discoid lupus, dysautonomia, endometriosis, essential mixed cryoglobulinemia, fibromyalgia-fibromyositis, Goodpasture' s syndrome, Grave's disease, Guillain-Barre syndrome (GBS), Hashimoto' s thyroiditis, Hidradenitis suppurativa, idiopathic and/or acute thrombocytopenic purpura, idiopathic pulmonary fibrosis, IgA neuropathy, interstitial cystitis, juvenile arthritis, Kawasaki's disease, lichen planus, Lyme disease, Meniere disease, mixed connective tissue disease (MCTD), myasthenia gravis, neuromyotonia, opsoclonus myoclonus syndrome (OMS), optic neuritis, Ord's thyroiditis, pemphigus vulgaris, pernicious anemia, polychondritis, polymyositis and dermatomyositis, primary biliary cirrhosis, polyarteritis nodosa, polyglandular syndromes, polymyalgia rheumatica, primary agammaglobulinemia, Raynaud phenomenon, Reiter' s syndrome, rheumatic fever, sarcoidosis, scleroderma, Sjogren's syndrome, stiff person syndrome, Takayasu's arteritis, temporal arteritis (also known as "giant cell arteritis"), ulcerative colitis, collagenous colitis, uveitis, vasculitis, vitiligo, vulvodynia ("vulvar vestibulitis"), and Wegener' s granulomatosis.

Routes of Administration and Dosing

Antibodies, or antigen-binding fragments thereof, or described herein can be administered to a patient (e.g., a human patient suffering from cancer, an autoimmune disease, or in need of hematopoietic stem cell transplant therapy) in a variety of dosage forms. For instance, antibodies, or antigen-binding fragments thereof, described herein can be administered to a patient suffering from cancer, an autoimmune disease, or in need of hematopoietic stem cell transplant therapy in the form of an aqueous solution, such as an aqueous solution containing one or more

pharmaceutically acceptable excipients. Pharmaceutically acceptable excipients for use with the compositions and methods described herein include viscosity-modifying agents. The aqueous solution may be sterilized using techniques known in the art.

Pharmaceutical formulations comprising anti-CD1 17 antibodies as described herein are prepared by mixing such anti-CD1 17 antibody with one or more optional pharmaceutically acceptable carriers (Remington's Pharmaceutical Sciences 16th edition, Osol, A. Ed. (1980)), in the form of lyophilized formulations or aqueous solutions. Pharmaceutically acceptable carriers are generally nontoxic to recipients at the dosages and concentrations employed, and include, but are not limited to: buffers such as phosphate, citrate, and other organic acids; antioxidants including ascorbic acid and methionine; preservatives (such as octadecyldimethylbenzyl ammonium chloride; hexamethonium chloride; benzalkonium chloride; benzethonium chloride; phenol, butyl or benzyl alcohol; alkyl parabens such as methyl or propyl paraben; catechol; resorcinol;

cyclohexanol; 3-pentanol; and m-cresol); low molecular weight (less than about 10 residues) polypeptides; proteins, such as serum albumin, gelatin, or immunoglobulins; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and other carbohydrates including glucose, mannose, or dextrins; chelating agents such as EDTA; sugars such as sucrose, mannitol, trehalose or sorbitol; salt-forming counter-ions such as sodium; metal complexes (e.g. Zn-protein complexes); and/or non-ionic surfactants such as polyethylene glycol (PEG).

The antibodies, or antigen-binding fragments, described herein may be administered by a variety of routes, such as orally, transdermal^, subcutaneously, intranasally, intravenously, intramuscularly, intraocularly, or parenterally. The most suitable route for administration in any given case will depend on the particular antibody, or antigen-binding fragment, administered, the patient, pharmaceutical formulation methods, administration methods (e.g., administration time and administration route), the patient's age, body weight, sex, severity of the diseases being treated, the patient's diet, and the patient's excretion rate.

The effective dose of an antibody, or antigen-binding fragment thereof, described herein can range, for example from about 0.001 to about 100 mg/kg of body weight per single (e.g., bolus) administration, multiple administrations, or continuous administration, or to achieve an optimal serum concentration (e.g., a serum concentration of 0.0001 -5000 g/mL) of the antibody, antigen-binding fragment thereof. The dose may be administered one or more times (e.g., 2-10 times) per day, week, or month to a subject (e.g., a human) suffering from cancer, an autoimmune disease, or undergoing conditioning therapy in preparation for receipt of a hematopoietic stem cell transplant. In the case of a conditioning procedure prior to hematopoietic stem cell

transplantation, the antibody, or antigen-binding fragment thereof, can be administered to the patient at a time that optimally promotes engraftment of the exogenous hematopoietic stem cells, for instance, from 1 hour to 1 week (e.g., 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 1 1 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours, 2 days, 3 days, 4 days, 5 days, 6 days, or 7 days) or more prior to administration of the exogenous hematopoietic stem cell transplant.

Examples

The data provided in Figs. 1 , 9, and 10 disclosed herein represent data based on the compositions and methods described herein, including the sequences disclosed in Tables 1 and 2, and are intended to be purely exemplary of the invention and are not intended to limit the scope of what the inventors regard as their invention.

Example 1. Analysis of Non-Human Primate Pharmacokinetics

A non-human primate pharmacokinetic assay was performed to determine the change in the concentration (ng/mL) of a isotype control antibody (i.e., "wild type antibody") compared to an Fc-modified CK6 variant antibody (i.e., an H435A Fc mutation; variant refers to the Fc

modification) to posess a shorter half life as a function time (post-administration). The results in Fig. 2 demonstrate that the CK6 variant antibody is characterized by a significantly shorter half-life in a non-human primate.

Example 2. Identification of Novel Anti-CD117 Antibodies

A human Fab phage display library was created based on a derivative of the human CK6 antibody (i.e., HC-1/LC-1 (Ab1 ) in order to identify improved anti-CD1 17 antibodies that had better affinity properties than CK6 while maintaining the functional antagonistic and internalizing characteristics of CK6. The CK6 derivative used as the bases for the screen was Ab1 , which is a variant of CK6 containing conservative amino acid substitutions within the light chain and heavy chain variable regions. Once the library was established, the screening process was performed according to standard phage display affinity maturation methodology known in the art. Briefly, the HC-1 was combined with a mixed donor-derived pool of human kappa light chains. Phage display selections were subsequently performed to selectively identify clones with improved off-rates after iterative rounds of panning. Antibodies were then screened to identify novel anti-CD1 17 antibodies with altered affinity to human CD1 17, e.g., an improved off rate of the antibody while maintaining kinetic characteristics of the CK6 antibody, including internalization.

To confirm binding to the desired target, purified antibodies were analyzed for binding to purified recombinant human CD1 17 ectodomain by bio-layer interferometry (BLI). Binding analysis of the antibodies identified from the phage display campaigns revealed a number of derivatives with improved off-rate kinetics as compared to HC-1/LC-1 (Fig. 1 ). The apparent kinetic values are provided in Table 3, which lists the apparent monovalent affinity (K_D), apparent association rate (k_on), and apparent dissociation rate (k_dis) of the indicated purified IgG to purified human CD1 17 ectodomain (R&D Systems #332-SR) as measured by BLI.

Table 3

A subset of these antibodies were engineered to look at combinations of affinity modifying substitutions that had not been sampled in the phage display campaigns and may provide affinity benefit as cooperative sequence variations.. Antibodies 77, 79, and 81 (Ab77, Ab79, and Ab81 , respectively) representative examples of subsidiary derivatives and are described in more detail below.

Antibody 77 (having HC-77/LC-77)

The heavy chain variable region (VH) amino acid sequence of Antibody 77 (Ab77) is provided below as SEQ ID NO: 7. The VH CDR amino acid sequences of Ab77 are underlined below and are as follows: TYWIG (VH CDR1 ; SEQ ID NO: 163); IIYPGDSDTRYSPSFQG (VH CDR2; SEQ ID NO: 2); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab77 VH sequence

QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID NO: 7) The light chain variable region (VL) amino acid sequence of Ab77 is provided below as SEQ ID NO 91 . The VL CDR amino acid sequences of Ab77 underlined below and are as follows: RASQGVISALA (VL CDR1 ; SEQ ID NO: 164); DASILES (VL CDR2; SEQ ID NO: 165); and QQFNSYPLT (VL CDR3; SEQ ID NO: 166).

Ab77 VL sequence

DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQQKPGKAPKLLIYDASILESGVPSRFSGSG SGTDFTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK (SEQ ID NO: 91 )

Antibody 79 (having HC79/LC79)

The heavy chain variable region (VH) amino acid sequence of Ab79 is provided below as SEQ ID NO: 7. The VH CDR amino acid sequences of Ab79 are underlined below and are as follows: TYWIG (VH CDR1 ; SEQ ID NO: 163); IIYPGDSDTRYSPSFQG (VH CDR2; SEQ ID NO: 2); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab79 VH sequence

QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID NO: 7)

The light chain variable region (VL) amino acid sequence of Ab79 is provided below as SEQ ID NO: 93. The VL CDR amino acid sequences of Ab79 underlined below and are as follows: RASQGVGSALA (VL CDR1 ; SEQ ID NO: 167); DASILES (VL CDR2; SEQ ID NO: 165); and QQFNSYPLT (VL CDR3; SEQ ID NO: 166).

Ab79 VL sequence

DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWYQQKPGKAPKLLIYDASILESGVPSRFSGSG SGTDFTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK (SEQ ID NO: 93)

Antibody 81 (having HC-81/LC-81)

The heavy chain variable region (VH) amino acid sequence of Ab81 is provided below as SEQ ID NO: 7. The VH CDR amino acid sequences of Ab81 underlined below and are as follows: TYWIG (VH CDR1 ; SEQ ID NO: 163); IIYPGDSDTRYSPSFQG (VH CDR2; SEQ ID NO: 2); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab81 VH sequence QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTMVTVSS (SEQ ID NO: 7)

The light chain variable region (VL) amino acid sequence of Ab81 is provided below as SEQ ID NO 95. The VL CDR amino acid sequences of Ab81 underlined below and are as follows: RASQGVISALA (VL CDR1 ; SEQ ID NO: 164); DASTLES (VL CDR2; SEQ ID NO: 168); and QQFNSYPLT (VL CDR3; SEQ ID NO: 166).

Ab81 VL sequence

DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQQKPGKAPKLLIYDASTLESGVPSRFSGSG SGTDFTLTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK (SEQ ID NO: 95)

This subset of clones consisting of library output iterations in the CDR1 and CDR2 of the light chain allowed for the analysis of cooperative substitutions in subsequent in vitro binding assays.

Example 3. In Vitro Antibody Binding Studies

Antibodies identified in Example 2 were tested for binding. Antibody binding studies were performed at 25 degrees Celsius in 1 x PBS supplemented with 0.1 % w/v bovine serum albumin with a Pall ForteBio Octet Red96 using biolayer interferometry (BLI). The indicated purified human antibody (as an lgG1 ) was immobilized onto anti-human Fc biosensors (AHC; Pall ForteBio 18- 5063) and incubated with 33.3 nM and 1 1 nM CD1 17 ectodomain (R&D Systems #332-SR)

The resulting binding intervals, which represented the association and dissociation curves were depicted in Fig. 3. The apparent monovalent affinity (KD), apparent association rate (kon), and apparent dissociation rate (kdis) are determined by local full fitting with a 1 :1 binding mode as calculated by Fortebio data analysis software version 10 of the indicated purified IgG (i.e., the HC- 77/LC-106 IgG; HC-109/LC-1 10 IgG; and HC-1 13/LC-1 14 IgG) to purified human CD1 17 ectodomain (R&D Systems #332-SR) were depicted in Table 4. Table 4 lists the apparent monovalent affinity (K_D), apparent association rate (k_on), and apparent dissociation rate (k_dis) of the indicated purified IgG to purified human CD1 17 ectodomain (R&D Systems #332-SR). The results demonstrate a purified IgG (i.e., the HC-77/LC-77 IgG; HC-79/LC-79 IgG; and HC-81 /LC-81 IgG) binds with high affinity to the purified human CD1 17 ectodomain and is characterized by a significantly slower kdis(1 /s) when compared to the HC-1 / LC-1 purified IgG. Table 4

As described in Table 4, each of antibodies Ab77, Ab79, and Ab81 had improved binding (K_D) compared to parent antibody Ab1 . Surprisingly, the high level of affinity was maintained, while improving the dissociation rate.

Example 4. Identification of Anti-CD117 Antibody 85 (Ab85), Anti-CD117 Antibody 86 (Ab86), Anti-CD117 Antibody 87 (Ab87), Anti-CD117 Antibody 88 (Ab88), and Anti-CD117 Antibody 89 (Ab89)

In addition to the screen described in Examples 2 and 3, a second screen based on antibody CK6 was also performed. An scFv phage display library was created based on a derivative of the human CK6 antibody (as in Example 2 the CK6 variant was Ab1 ). Briefly, a small synthetic library of CDRH3 variants was generated to remove a potential deamidation site (NG) and was introduced into a large diversity library of either the IGHV5-51 or the IGHV1 -46 human framework. This screen was a challenge given the position of the amino acid in the CDR3 region of the heavy chain. The synthetic library was combined with a large diversity library of the IGKV1 - 39 light chain human framework. Phage display selections were then performed to selectively identify clones with improved off-rates after iterative rounds of panning. Antibodies were then screened to identify novel anti-CD1 17 antibodies with improved affinity to human CD1 17. Certain antibodies, including the antibodies identified below, were identified using the screen.

Antibodies 85 (Ab85), 86 (Ab86), 87 (Ab87), 88 (Ab88), and 89 (Ab89) were identified in the screen as a novel therapeutic human anti-CD1 17 antibody. The heavy chain and light chain variable regions of Ab85, Ab86, Ab87, Ab88, and Ab89 (including the CDR domains) are described below in Table 5.

Table 5

Antibody BackAmino acid sequence

name bone

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWV RQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTISADK

HC-85 hlgG1 SISTAYLQWSSLKASDTAMYYCARHGRGYEGYEGAFDI Antibody BackAmino acid sequence

name bone

WGQGTLVTVSS (SEQ ID NO: 143)

DIQMTQSPSSLSASVGDRVTITCRSSQGIRSDLGWYQQ KPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISS LQPEDFATYYCQQANGFPLTFGGGTKVEIK (SEQ ID

LC-85 h Kappa NO: 144)

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWV RQMPGKGLEWMGIIYPGDSDIRYSPSLQGQVTISVDTS TSTAYLQWNSLKPSDTAMYYCARHGRGYNGYEGAFDI

HC-86 hlgG1 WGQGTLVTVSS (SEQ ID NO: 151 )

DIQMTQSPSSLSASVGDRVTITCRASQGIGDSLAWYQQ KPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISS LQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID

LC-86 h Kappa NO: 152)

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWV RQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTISADK SISTAYLQWSSLKASDTAMYYCARHGRGYEGYEGAFDI

HC-87 hlgG1 WGQGTLVTVSS (SEQ ID NO: 143)

DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQ KPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTLTISS LQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID

LC-87 h Kappa NO: 156)

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWV RQMPGKGLEWMGIIYPGDSLTRYSPSFQGQVTISADKS ISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDI

HC-88 hlgG1 WGQGTLVTVSS (SEQ ID NO: 158)

LC-88 h Kappa NO: 156)

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWV RQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADK SISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDI

HC-89 hlgG1 WGQGTLVTVSS (SEQ ID NO: 160)

LC-89 h Kappa NO: 152)

Antibody HC-85/LC-85 (Ab 85)

The heavy chain variable region (VH) amino acid sequence of Ab85 is provided below as SEQ ID NO: 143. The VH CDR amino acid sequences of Ab85 underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IINPRDSDTRYRPSFQG (VH CDR2; SEQ ID NO: 146); and HGRGYEGYEGAFDI (VH CDR3; SEQ ID NO: 147).

Ab85 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMAIINPRDSDTRYRPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGRGYEGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 143) The light chain variable region (VL) amino acid sequence of Ab85 is provided below as SEQ ID NO 144. The VL CDR amino acid sequences of Ab85 underlined below and are as follows: RSSQGIRSDLG (VL CDR1 ; SEQ ID NO: 148); DASNLET (VL CDR2; SEQ ID NO: 149); and QQANGFPLT (VL CDR3; SEQ ID NO: 150).

Ab85 VL sequence

Antibody HC-86/LC-86 (Ab86)

The heavy chain variable region (VH) amino acid sequence of Ab86 is provided below as SEQ ID NO: 151 . The VH CDR amino acid sequences Ab86 underlined below and are as follows: NYWIG (VH CDR1 ; SEQ ID NO: 145); IIYPGDSDIRYSPSLQG (VH CDR2; SEQ ID NO: 153); and HGRGYNGYEGAFDI (VH CDR3; SEQ ID NO: 3).

Ab86 VH sequence

The light chain variable region (VL) amino acid sequence of Ab86 is provided below as SEQ ID NO 152. The VL CDR amino acid sequences of Ab86 underlined below and are as follows: RASQGIGDSLA (VL CDR1 ; SEQ ID NO: 154); DASNLET (VL CDR2; SEQ ID NO: 149); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab86 VL sequence

Antibody HC-87/LC-87 (Ab87)

Ab87 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMAIINPRDSDTRYRPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGRGYEGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 143) The light chain variable region (VL) amino acid sequence of Ab87 is provided below as SEQ ID NO 156. The VL CDR amino acid sequences of Ab87 underlined below and are as follows: RASQGIRNDLG (VL CDR1 ; SEQ ID NO: 157); DASSLES (VL CDR2; SEQ ID NO: 5); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab87 VL sequence

Antibody HC-88/LC-88 (Ab88)

Ab88 VH sequence

The light chain variable region (VL) amino acid sequence of Ab88 is provided below as SEQ ID NO: 156. The VL CDR amino acid sequences of Ab88 underlined below and are as follows: RASQGIRNDLG (VL CDR1 ; SEQ ID NO: 157); DASSLES (VL CDR2; SEQ ID NO: 5); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab88 VL sequence

Antibody HC-89/LC-89 (Ab89)

Ab89 VH sequence

EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSF QGQVTISADKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDIWGQGTLVTVSS (SEQ ID NO: 160) The light chain variable region (VL) amino acid sequence of Ab89 is provided below as SEQ ID NO: 152. The VL CDR amino acid sequences of Ab89 underlined below and are as follows: RASQGIGDSLA (VL CDR1 ; SEQ ID NO: 154); DASNLET (VL CDR2; SEQ ID NO: 149); and QQLNGYPIT (VL CDR3; SEQ ID NO: 155).

Ab89 VL sequence

DIQMTQSPSSLSASVGDRVTITCRASQGIGDSLAWYQQKPGKAPKLLIYDASNLETGVPSRFSGS GSGTDFTLTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK (SEQ ID NO: 152).

Example 5. In vitro Binding Studies of Antibody 85, Antibody 86, Antibody 87, Antibody 88, and Antibody 89

Ab85, Ab86, Ab87, Ab88, and Ab89 were further studied for binding characteristics using standard Octet binding. Antibody binding studies were performed at 25 degrees Celsius in 1 x PBS supplemented with 0.1 % w/v bovine serum albumin with a Pall ForteBio Octet Red96 using biolayer interferometry (BLI). The indicated purified human antibody was immobilized onto anti- human Fc biosensors (AHC; Pall ForteBio 18-5063) and incubated with 33.3 nM (top traces) and 1 1 nM (bottom traces) CD1 17 ectodomain (R&D Systems #332-SR).The resulting binding intervals, which represented the association and dissociation curves were depicted in Figs. 4A (i.e., HC-85/LC-85) and 4B (i.e., HC-1 /LC-1 ). The apparent monovalent affinity (K_D), apparent association rate (kon), and apparent dissociation rate (kdis) of the indicated purified IgG (i.e., HC- 85/LC-85) to purified human CD1 17 ectodomain (R&D Systems #332-SR) compared to a control (i.e., HC-1/LC-1 ) were depicted in Table 6. The results demonstrate a purified IgG (i.e., the HC- 85/LC-85 IgG) binds with high affinity to the purified human CD1 17 ectodomain and is

characterized by a slow kdis (1/s) relative to the parent Ab1 antibody. Thus, despite the modification in the HCDR3, binding affinity was improved, i.e., with a slower dissociation rate, and the deamidation site was removed.

Table 6

A comparison of the amino acid sequences of the heavy and light chain variable regions and CDRs of Ab85 and Ab1 is described in Figs. 5A and 5B. Example 6. Identification of Novel Anti-CD117 Antibodies

Having identified a number of improved anti-CD1 17 antibodies derived from anti-CD1 17 antibody CK6, combinations of antigen binding regions (variable regions) from antibodies identified in Examples 2-5 were then tested for binding.

To identify further anti-CD1 17 antibodies with advantageous therapeutic properties, heavy chain and light chain sequences disclosed here were mixed and matched to create novel anti- CD1 17 antibodies. The following antibodies were identified from this process as preferred anti- CD1 17 antibodies: HC-245/LC-245 (i.e., Ab245), HC-246/LC-246 (i.e., Ab246), HC-247/LC-247 (i.e., Ab247), HC-248/LC-248 (i.e., Ab248), and HC-249/LC-249 (i.e., Ab249).

Table 7

Antibody BackAmino acid sequence

name bone

EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGWV RQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADK SISTAYLQWSSLKASDTAMYYCARHGLGYNGYEGAFDI

HC-245 hlgG1 WGQGTLVTVSS (SEQ ID NO: 98)

DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQ KPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFTLTISS LQPEDFATYYCQQFNGYPLTFGQGTRLEIK (SEQ ID

LC-245 h Kappa NO: 99)

QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIGWV RQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISAGK SISTAYLQWSSLKASDTAMYYCARHGRGYNGYEGAFDI

HC-246 hlgG1 WGQGTMVTVSS (SEQ ID NO: 7)

LC-246 h Kappa NO: 99)

HC-247 hlgG1 WGQGTMVTVSS (SEQ ID NO: 7)

DIQMTQSPSSLSASVGDRVTITCRASRGISDYLAWYQQ KPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFTLTISS LQPEDFATYYCQQANSFPITFGQGTRLEIK (SEQ ID

LC-247 h Kappa NO: 100)

HC-248 hlgG1 WGQGTLVTVSS (SEQ ID NO: 98)

DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQ KPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFTLTISS LQPEDFATYYCQQLNGYPLTFGQGTRLEIK (SEQ ID

LC-248 h Kappa NO: 101 )

HC-249 hlgG1 WGQGTLVTVSS (SEQ ID NO: 98)

LC-249 h Kappa DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWYQQ

Figs. 5C and 5D provide an alignment of the heavy and light chain variable regions of CK6 and Ab249.

Example 7: Kinetic Analysis of Affinity-Improved anti-CD117 Antibodies

To differentiate amongst the affinity matured anti-CD1 17 antibodies, the monovalent binding kinetics were determined by biolayer interferometry in comparison to the CK6 derivative Ab1 (HC-1 , LC-1 ). HC-77/LC-77 (i.e. Ab77), HC-79/LC-79 (i.e. Ab79), HC-81 /LC-81 (i.e. Ab81 ), HC-85/LC-85 (i.e. Ab85), HC-245/LC-245 (i.e. Ab245), HC-246/LC-246 (i.e. Ab246), HC-247/LC- 247 (i.e. Ab247), HC-248/LC-248 (i.e. Ab248), and HC-249/LC-249 (i.e. Ab249) and HC-1/LC-1 (i.e. Ab1 ) were immobilized onto anti-human Fc biosensors (AHC; Pall ForteBio 18-5063) and incubated with 33 nM and 1 1 nM CD1 17 purified ectodomain (R&D Systems #332-SR).

The apparent monovalent affinity (KD), apparent association rate (Kon) and apparent dissociation rate (kdis) are tabulated in Table 8. For each antibody the improvement in apparent dissociation rate compared to HC-1 /LC-1 (i.e. Ab1 ) was calculated. The HC-249/LC-249 antibody (i.e. Ab249) demonstrated the most improved off-rate and the highest apparent monovalent affinity. The HC-85/LC-85 antibody (i.e. Ab85) had the highest apparent association rate amongst the set of antibodies tested in comparison to Ab1 and also had the deamidation site within the heavy chain CDR3 removed. The resulting sensorgrams, which represent the association and dissociation curves, are shown for CK6 derivative (HC-1/LC-1 , i.e. Ab1 ), the HC-85/LC-85 antibody (i.e. Ab85), and the HC-249/LC-249 antibody (i.e. Ab249) (Figs. 6A, 6B and 6C).

Table 8

HC-246 / LC-246 7.08x10^"10 3.61 x10⁵ 2.55x10^"4 8.9

HC-247 / LC-247 1 .68x10^"9 3.74x10⁵ 6.30x10^"4 3.6

HC-248 / LC-248 9.22x10^"10 3.46x10^s 3.19x10^"4 7.1

HC-249 / LC-249 5.51 x10^"10 3.44x10⁵ 1 .89x10^"4 12

As described in Table 8, the off rate of Ab249 was significantly improved over the parent antibody, Ab1 , where the rate was about 12 fold slower than the parent.

Example 8: Characterization of Charge Variants of Anti-CD117 Antibodies

Capillary isoelectric focusing was performed on a subset of affinity-improved anti-CD1 17 antibodies to determine if sequence differentiation impacted the biophysical properties of the antibodies. Briefly, 10-40 micrograms of antibody were subjected to 7- and 15-days incubation at 25 or 50 degrees Celsius and analyzed through a capillary electrophoresis method using the Maurice instrument manufactured by Protein Simple according to standard manufacturer instruction. Antibody samples migrate to their electrically neutral pH. The fraction of acidic variants was calculated based on absorbance peaks detected below the isoelectric point relative to the total injected sample.

The CK6 derivative Ab1 (HC-1/LC-1 ) exhibited 26% acidic species at the start of the assay and this fraction increased to 57% and 54% of total injected antibody after 7 days of incubation at 25 and 50 degrees Celsius, respectively. With extended incubation for 15 days, the fraction of acidic variants for CK6 increased to 68% and 78% total injected antibody at 25 and 50 degrees Celsius, respectively.

In comparison, the HC-85/LC-85 antibody (i.e., Ab85) demonstrated significantly lower starting fractions of acidic variants (6.9% at TO) and reduced accumulation of acidic variants at 25 degrees Celsius (16% at day 7; 18% at day 15) and at 50 degrees Celsius (36% at day 7; 50% at day 15).

The HC-249/LC-249 antibody (i.e., Ab249) exhibited higher fractions of acidic variants at the start of the experiment than Ab85 (31 %), however, these fractions did not significantly increase following incubation at 25 degrees Celsius (35% at day 7; 23% at day 15). After stress at 50 degrees Celsius, the acidic species increased for Ab249 at both day 7 and day 15 (52% and 65%; respectively).

The antibodies tested in this example were tested as lgG1 antibodies with the same heavy and light constant regions described in SEQ ID NOs: 169 and 183, respectively. Thus, the observed variation in stability reflected in the percentage of acidic variant as tested was due to the variable regions. Of all the antibodies analyzed, Ab85 had the lowest fraction of acidic variants and the least accumulation of these species following stress conditions as described in Figs. 7 A and 7B.

Example 9: Characterization of Hydrophobicity of Anti-CD117 Antibodies

A subset of the affinity improved anti-CD1 17 antibodies was evaluated after incubation at 25 or 50 degrees Celsius for 15 days by hydrophobic interaction chromatography (HIC). Briefly, 50 micrograms of the indicated antibody were injected onto a Tosoh TSKgel Phenyl-5PW 7.5 mm ID x 7.5 cm 10-micron column (Catalog # 07573) on a Waters ARC HPLC/UPLC system. For the CK6 variant (Ab1 ; HC-1 /LC-1 ), peak broadening was observed after 15 days of incubation at 25 and 50 degrees Celsius. For affinity improved antibodies HC-77/LC-77 (i.e., Ab 77), HC-79/LC-79 (i.e., Ab79), and HC-81/LC-81 (i.e., Ab 81 ), significant peak broadening was evident in the

chromatograms for both mild (25 degrees Celsius) and severe (50 degrees Celsius) conditions. Ab85 demonstrated minimal peak broadening after incubation at 25 or 50 degrees Celsius after 15 days, exhibiting the lowest change in hydrophobicity of the affinity improved anti-CD1 17 antibodies tested and compared to the CK6 variant Ab1 (HC-1/LC-1 ) as described in Figs. 8A - 8E. As described in Example 8, the antibodies contained the same constant region sequences.

Thus, the anti-CD1 17 antibodies Ab85 and Ab249 exhibited marked improvements in monovalent affinity (Figs. 6B and 6C), and superior biophysical behavior as measured by acidic variants and hydrophobicity under thermal stress (Figs. 7A and 7B and Figs. 8A - 8E). Further, Ab85 had an improved HC CDR3 domain as a potential deamidation site was removed without negatively impacting the characteristics of the antibody.

Example 10. Identification of Novel Anti-CD117 Antibodies by Rat Immunization

As a third strategy, to identify novel anti-CD1 17 antibodies, 5 rats were immunized with synthetic DNA coding for human CD1 17 ectodomain (aa26-524; P010721 ) and hybridoma fusions were prepared according to standard methods known in the art. Hybridomas were screened for binding to cell lines expressing human CD1 17 ectodomain (aa26-524; PO10721 ) and

cynomologus monkey CD1 17 ectodomain (aa26-521 ; F6V858) to identify antibodies which would proceed in screening. The following antibodies were identified as positive binders to both cell lines by flow cytometery: HC-17/LC-17 (i.e., Ab17), HC-18/LC-18 (i.e., Ab18), HC-19/LC-19 (i.e., Ab19), HC-20/LC-20 (i.e., Ab20), HC-21/LC-21 (i.e., Ab21 ), HC-22/LC-22 (i.e., Ab22), HC-23/LC-23 (i.e., Ab23), HC-24/LC-24 (i.e., Ab24), HC-25/LC-25 (i.e., Ab25), HC-27/LC-27 (i.e., Ab27), and HC- 28/LC-28 (i.e., Ab28).

To confirm binding to the desired target, purified antibodies were analyzed for binding to purified recombinant CD1 17 ectodomain by bio-layer interferometry. Binding analysis of the antibodies identified from the rat immunizations reveals a wide set of association and dissociation kinetics as demonstrated in Figs. 9 and 10. The apparent kinetic values are provided in Table 3 and Table 9. Table 9 provides a table listing the apparent monovalent affinity (K_D), apparent association rate (k_on), and apparent dissociation rate (k_dis) of the indicated purified IgG to purified rhesus CD1 17 ectodomain. As provided above, Table 3 provides a table listing the apparent monovalent affinity (K_D), apparent association rate (k_on), and apparent dissociation rate (k_dis) the indicated purified IgG (including the antibodies identified in this Example) to purified human CD1 17 ectodomain.

Table 9

To confirm the species cross-reactivity of the antibodies identified in the screening of the rat hybridomas, purified antibodies were analyzed for binding to purified rhesus CD1 17

ectodomain by bio-layer interferometry. Binding analysis of the antibodies demonstrates strong cross-reactivity for the set of antibodies. Analysis of the apparent kinetic values for binding to rhesus antigen (Table 9) demonstrates strong correlation with the apparent association and dissociation rates observed for binding to the human antigen (Table 3).

TABLE 10: AMINO ACID SEQUENCE SUMMARY

Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable AIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY N0:1 1 region of LC-4 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNSYPLTFGGGTKVDIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-5 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable NIQMTQSPSSLSASVGDRVTITCRASQAISDYLAWF N0:12 region of LC-5 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-6 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable AIRMTQSPSSLSASVGDRVIIACRASQGIGGALAWY N0:13 region of LC-6 QQKPGNAPKVLVYDASTLESGVPSRFSGGGSGTDF

TLTISSLQPEDFATYYCQQFNSYPLTFGGGTKLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-7 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIAMTQSPPSLSAFVGDRVTITCRASQGIISSLAWYQ N0:14 region of LC-7 QKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTL

TIRSLQPEDFATYYCQQFNSYPLTFGGGTKLEIK

Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI

SEQ ID N0:7

HC-8 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGISSALAWY N0:15 region of LC-8 QQKAGKAPKVLISDASSLESGVPSRFSGSGSGTDFT

LSISSLQPEDFATYYCQQFNGYPLTFGGGTKVDIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-9 amino acid SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG sequence YEGAFDIWGQGTMVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable AIRMTQSPSSLSASVGDRVTITCQASQGIRNDLGWY N0:16 region of LC-9 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

FTISSLQPEDIATYYCQQFNSYPLTFGGGTKLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-10 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable NIQMTQSPSSLSTSVGDRVTITCRASQGIGTSLAWY N0:17 region of LC-10 QQKPGKPPKLLIYDASSLESGVPSRLSGSGSGTDFT

LTISSLQPEDFATYYCQQSNSYPITFGQGTRLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-1 1 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable AIQLTQSPSSLSASVGDRVTITCRASQSIGDYLTWYQ N0:18 region of LC-1 1 QKPGKAPKVLIYGASSLQSGVPPRFSGSGSGTDFTL

TVSSLQPEDFATYYCQQLNSYPLTFGGGTKLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-12 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVRSTLAWY N0:19 region of LC-12 QQKPGKAPKLLIYDASILESGVPSRFSGSGSGTDFTL

TISSLQPEDFATYYCQQFNGYPLTFGQGTRLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-13 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIVMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:20 region of LC-13 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNSYPLTFGGGTKLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-14 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGISSFLAWYQ N0:21 region of LC-14 QKPGKAPKLLIYDASTLQSGVPSRFSGSASGTDFTL

TISSLQPEDFATYYCQQLNGYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-15 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable AIQLTQSPSSLSASVGDRVTITCRASQGIGSALAWYQ NO:22 region of LC-15 QKPGIGPKLLIYDASTLESGVPARFSGSGSRTDFTLTI

TSLQPEDFATYYCQQFNGYPLTFGGGTKLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-16 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable AIQLTQSPSSLSASVGDRVTITCRASQGITSALAWYQ NO:23 region of LC-16 EKPGKAPNLLIYDASSLESGVPSRFSGSGYGTDFTL

TISSLQPEDFATYYCQQLNSYPLTFGGGTKVDIK

SEQ ID Heavy chain QIQLVQSGPELRKPGESVKISCKASGYTFTDYAMYW NO:24 variable region of VKQAPGKGLKWMGWINTYTGKPTYADDFKGRFVFS

HC-17 LE AS ANTAN LQ ISN LKN E DTATYFCARARG LVDDYV

MDAWGQGTSVTVSS

SEQ ID Light chain variable SYELIQPPSASVTLGNTVSLTCVGDELSKRYAQWYQ NO:25 region of LC-17 QKPDKTIVSVIYKDSERPSGISDRFSGSSSGTTATLTI

HGTLAEDEADYYCLSTYSDDNLPVFGGGTKLTVL

SEQ ID Heavy chain EVQLQQYGAELGKPGTSVRLSCKVSGYNIRNTYIHW NO:26 variable region of VNQRPGEGLEWIGRIDPTNGNTISAEKFKTKATLTAD

HC-18 TSSHTAYLQFSQLKSDDTAIYFCALNYEGYADYWGQ

GVMVTGSS

SEQ ID Light chain variable DIQMTQSPSFLSASVGDRVTINCKASQNINKYLNWY NO:27 region of LC-18 QQKVGEAPKRLIFKTNSLQTGIPSRFSGSGSGTDYT

LTISSLQTEDVATYFCFQYNIGYTFGAGTKVELK

SEQ ID Heavy chain EVQLQESGPGLVKPSQSLSLTCSVTGYSISSNYRWN NO:28 variable region of WIRKFPGNKVEWMGYINSAGSTNYNPSLKSRISMTR

HC-19 DTSKNQFFLQVNSVTTEDTATYYCARSLRGYITDYS

GFFDYWGQGVMVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable D I RMTQS P AS LS AS LG ET VN I EC L AS E D I FS D LAW YQ NO:29 region of LC-19 QKPGKSPQLLIYNANSLQNGVPSRFSGSGSGTRYSL

KINSLQSEDVATYFCQQYKNYPLTFGSGTKLEIK

SEQ ID Heavy chain EVQLQQYGAELGKPGTSVRLSCKLSGYKIRNTYIHW NO:30 variable region of VNQRPGKGLEWIGRIDPANGNTIYAEKFKSKVTLTAD

HC-20 TSSNTAYMQLSQLKSDDTALYFCAMNYEGYEDYWG

QGVMVTVSS

SEQ ID Light chain variable DIQMTQSPSFLSASVGDSVTINCKASQNINKYLNWY N0:31 region of LC-20 QQKLGEAPKRLIHKTDSLQTGIPSRFSGSGSGTDYT

LTISSLQPEDVATYFCFQYKSGFMFGAGTKLELK

SEQ ID Heavy chain QIQLVQSGPELKKPGESVKISCKASGYTFTDYAVYW NO:32 variable region of VIQAPGKGLKWMGWINTYTGKPTYADDFKGRFVFSL

HC-21 ETSASTANLQISNLKNEDTATYFCARGAGMTKDYVM

DAWGRGVLVTVS

SEQ ID Light chain variable SYELIQPPSASVTLGNTVSLTCVGDELSKRYAQWYQ NO:33 region of LC-21 QKPDKTIVSVIYKDSERPSDISDRFSGSSSGTTATLTI

HGTLAEDEADYYCLSTYSDDNLPVFGGGTKLTVL

SEQ ID Heavy chain QVQLKESGPGLVQPSQTLSLTCTVSGFSLTSYLVHW NO:34 variable region of VRQPPGKTLEWVGLMWNDGDTSYNSALKSRLSISR

HC-22 DTSKSQVFLKMHSLQAEDTATYYCARESNLGFTYW

GHGTLVTVSS

SEQ ID Light chain variable DIQMTQSPASLSASLEEIVTITCKASQGIDDDLSWYQ NO:35 region of LC-22 QKPGKSPQLLIYDVTRLADGVPSRFSGSRSGTQYSL

KISRPQVADSGIYYCLQSYSTPYTFGAGTKLELK

SEQ ID Heavy chain EVQLQQYGAELGKPGTSVRLSCKVSGYNIRNTYIHW NO:36 variable region of VHQRPGEGLEWIGRIDPTNGNTISAEKFKSKATLTAD

HC-23 TSSNTAYMQFSQLKSDDTAIYFCAMNYEGYADYWG

QGVMVTVSS

SEQ ID Light chain variable DIQMTQSPSFLSASVGDRLTINCKASQNINKYLNWY NO:37 region of LC-23 QQKLGEAPKRLIFKTNSLQTGIPSRFSGSGSGTDYTL

T I SS LQ P E D V AT YFC FQYN I G FT FG AGT KL E L K

SEQ ID Heavy chain EVQLVESGGGLVQSGRSLKLSCAASGFTVSDYYMA NO:38 variable region of WVRQAPTKGLEWVATINYDGSTTYHRDSVKGRFTIS

HC-24 RDNAKSTLYLQMDSLRSEDTATYYCARHGDYGYHY

GAYYFDYWGQGVMVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIVLTQSPALAVSLGQRATISCRASQTVSLSGYNLIH NO:39 region of LC-24 WYQQRTGQQPKLLIYRASNLAPGIPARFSGSGSGTD

FTLTISPVQSDDIATYYCQQSRESWTFGGGTNLEMK

SEQ ID Heavy chain QIQLVQSGPELKKPGESVKISCKASGYTFTDYAIHWV NO:40 variable region of KQAPGQGLRWMAWINTETGKPTYADDFKGRFVFSL

HC-25 EASASTAHLQISNLKNEDTATFFCAGGSHWFAYWG

QGTLVTVSS

SEQ ID Light chain variable SYELIQPPSASVTLENTVSITCSGDELSNKYAHWYQ N0:41 region of LC-25 QKPDKTILEVIYNDSERPSGISDRFSGSSSGTTAILTI

RDAQAEDEADYYCLSTFSDDDLPIFGGGTKLTVL

HC-26 ETSASTANLQISNLKNEDTATYFCARGAGMTKDYVM

DAWGRGVLVTVS

SEQ ID Light chain variable SYELIQPPSTSVTLGNTVSLTCVGNELPKRYAYWFQ NO:42 region of LC-26 QKPDQSIVRLIYDDDRRPSGISDRFSGSSSGTTATLT

IRDAQAEDEAYYYCHSTYTDDKVPIFGGGTKLTVL

SEQ ID Heavy chain EVQLVESGGGLVQPGRSMKLSCKASGFTFSNYDMA NO:43 variable region of WVRQAPTRGLEWVASISYDGITAYYRDSVKGRFTIS

HC-27 RENAKSTLYLQLVSLRSEDTATYYCTTEGGYVYSGP

HYFDYWGQGVMVTVSS

SEQ ID Light chain variable DIQMTQSPSSMSVSLGDTVTITCRASQDVGIFVNWF NO:44 region of LC-27 QQKPGRSPRRMIYRATNLADGVPSRFSGSRSGSDY

SLTISSLESEDVADYHCLQYDEFPRTFGGGTKLELK

SEQ ID Heavy chain EVQLQQYGAELGKPGTSVRLSCKVSGYKIRNTYIHW NO:45 variable region of VNQRPGKGLEWIGRIDPANGNTIYAEKFKSKVTLTAD

HC-28 TSSNTAYMQLSQLKSDDTALYFCAMNYEGYEDYWG

QGVMVTVSS

SEQ ID Light chain variable DIQMTQSPSFLSASVGDSVTINCKASQNINKYLNWY NO:46 region of LC-28 QQKLGEAPKRLIHKTNSLQPGFPSRFSGSGSGTDYT

LTISSLQPEDVAAYFCFQYNSGFTFGAGTKLELK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTDYYIH NO:47 variable region of WVRQAPGQGLEWMGWMNPHSGDTGYAQKFQGR

HC-29 VTMTRDTSTSTVYMELSSLRSE DT A V Y YC A R H G RG

YNGYEGAFDIWGQGTLVTVSSAS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGNELGWY NO:48 region of LC-29 QQKPGKAPKLLIYAASNLQSGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQYDNLPLTFGQGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLH NO:49 variable region of WVRQAPGQGLEWMGWINPNSGDTNYAQNFQGRV

HC-30 TMTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGY

NGYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:50 region of LC-30 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPLTFGGGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYLH N0:51 variable region of WVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRV

HC-31 TMTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGY

EGYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:52 region of LC-31 QQKPGKAPKLLIYDASELETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIH NO:53 variable region of WVRQAPGQGLEWMGWLNPSGGGTSYAQKFQGRV

HC-32 TMTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGY

DGYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:54 region of LC-32 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPLTFGGGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFSTYYMH NO:55 variable region of WVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVT

HC-33 MTRDTSTSTVYMKLSSLRSEDTAVYYCARHGRGYE

GYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRDDLGWY NO:56 region of LC-33 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYIH NO:57 variable region of WVRQAPGQGLEWMGIINPSGGNTNYAQNFQGRVT

HC-34 MTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGYN

AYEGAFDIWGQGTLVTVSSAS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:58 region of LC-34 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQVNGYPLTFGGGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGGTFSSYAIS NO:59 variable region of WVRQAPGQGLEWMGVINPTVGGANYAQKFQGRVT

HC-35 MTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGYN

EYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCQASQDISDYLNWY NO:60 region of LC-35 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQGNSFPLTFGGGTKLEIK

SEQ ID Heavy chain QVQLVQSGAEVKKLGASVKVSCKASGYTFSSYYMH N0:61 variable region of WVRQAPGQGLEWMGVINPNGAGTNFAQKFQGRVT

HC-36 MTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGYE

GYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:50 region of LC-36 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPLTFGGGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTTYYMH NO:62 variable region of WVRQAPGQGLEWMGWINPTGGGTNYAQNFQGRV

HC-37 TMTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGY

EGYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDVSWY NO:63 region of LC-37 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLSGYPITFGQGTKLEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYIH NO:64 variable region of WVRQAPGQGLEWMGMINPSGGSTNYAQKFQGRVT

HC-38 MTRDTSTSTVYMELSSLRSEDTAVYYCARHGRGYN

DYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQSISDWLAWY NO:65 region of LC-38 QQKPGKAPKLLIYEASNLEGGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPYTFGQGTKVEIK

SEQ ID Heavy chain QVQLVQSGAEVKKPGASVKVSCKASGYIFSAYYIHW NO:66 variable region of VRQAPGQGLEWMGIINPSGGSTRYAQKFQGRVTMT

HC-39 RDTSTSTVYMELSSLRSEDTAVYYCARHGRGYGGY

EGAFDIWDQGTLVTVSSAS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGDYVAWY NO:67 region of LC-39 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPITFGQGTRLEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYRFTSYWIG NO:68 variable region of WVRQMPGKGLEWMGIIYPDDSDTRYSPSFQGQVTI

HC-40 SVDKSNSTAYLQWSSLKASDTAMYYCARHGRGYN

GYEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGISSYLAWY NO:69 region of LC-40 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTYFT

LTISSLQPEDFATYYCQQGASFPITFGQGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGSSFPNSWIAW NO:70 variable region of VRQMPGKGLEWMGIIYPSDSDTRYSPSFQGQVTISA

HC-41 DKSISTAYLQWSSLEASDTAMYYCARHGRGYNGYE

GAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNYLAWY N0:71 region of LC-41 QQKPGKAPKLLIYDASSLQSGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFDSYWIG NO:72 variable region of WVRQMPGKGLEWMGIMYPGDSDTRYSPSFQGQVT

HC-42 ISADKSISTAYLQWSSLKASDTAMYYCARHGRGYNA

YEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQSINNWLAWY NO:73 region of LC-42 QQKPGKAPKLLIYDAFILQSGVPSRFSGSGSGTDFTL

T I SS LQ P E D FATYYC LQ LNS YP LT FG PGT KV D I K

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTNWIAWV NO:74 variable region of RQMPGKGLEWMGIIYPGDSETRYSPSFQGQVTISAD

HC-43 KSISTAYLQWSSLKASDTAMYYCARHGRGYYGYEG

AFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGISDNLNWY NO:75 region of LC-43 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQAISFPLTFGQGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYNFTSYWIG NO:76 variable region of WVRQMPGKGLEWMGVIYPDDSETRYSPSFQGQVTI

HC-44 SADKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTLVTVSSAS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASRDIRDDLGWY NO:77 region of LC-44 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYTFNTYIGWV NO:78 variable region of RQMPGKGLEWMGIIYPGDSGTRYSPSFQGQVTISA

HC-45 DKAISTAYLQWSSLKASDTAMYYCARHSRGYNGYE

GAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGISNYLAWY NO:79 region of LC-45 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPVTFGQGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYNFTTYWIGW NO:80 variable region of VRQMPGKGLEWMGIIHPADSDTRYNPSFQGQVTISA

HC-46 DKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYE

GAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRVSQGISSYLAWY N0:81 region of LC-46 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYRFSNYWIA NO:82 variable region of WVRQMPGKGLEWMGIIYPDNSDTRYSPSFQGQVTI

HC-47 SADKSISTAYLQWSSLKASDTAMYYCARHGRGYDG

YEGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRSDLAWY NO:83 region of LC-47 QQKPGKAPKLLIYGASSLQSGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPLSFGQGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYRFASYWIG NO:84 variable region of WVRQMPGKGLEWMGITYPGDSETRYNPSQGQVTIS

HC-48 ADKSISTAYLQWSSLKASDTAMYYCARHGRGYGGY

EGAFDIWGQGTLVTVSSAS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:85 region of LC-48 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPLTFGGGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGW NO:86 variable region of VRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISA

HC-49 DKSISTAYLQWSSLKASDTAMYYCARHGRGYNGYE

GAFDIWGQGTLVTVSSAS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQSISNWLAWY NO:87 region of LC-49 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQTNSFPLTFGQGTRLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-74 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQ NO:88 region of LC-74 QKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTL

TISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-75 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGIRSALAWYQ NO:89 region of LC-75 QKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTL

TISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-76 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWY NO:90 region of LC-76 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-77 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQ N0:91 region of LC-77 QKPGKAPKLLIYDASILESGVPSRFSGSGSGTDFTLTI

SSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-78 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGIRSALAWYQ NO:92 region of LC-78 QKPGKAPKLLIYDASILESGVPSRFSGSGSGTDFTLTI

SSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-79 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWY NO:93 region of LC-79 QQKPGKAPKLLIYDASILESGVPSRFSGSGSGTDFTL

TISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-80 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQ NO:94 region of LC-80 QKPGKAPKLLIYDASILESGVPSRFSGSGSGTDFTLTI

SSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-81 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVISALAWYQ NO:95 region of LC-81 QKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFTL

TISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-82 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGIRSALAWYQ NO:96 region of LC-82 QKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFTL

TISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-83 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWY NO:97 region of LC-83 QQKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-84 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQLTQSPSSLSASVGDRVTITCRASQGVGSALAWY NO:97 region of LC-84 QQKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGW NO:98 variable region of VRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISA

HC-245 DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE

GAFDIWGQGTLVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWY NO:99 region of LC-245 QQKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNGYPLTFGQGTRLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-246 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWY NO:99 region of LC-246 QQKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQFNGYPLTFGQGTRLEIK

SEQ ID N0:7 Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTTYWIG variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI HC-247 SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTMVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASRGISDYLAWY NO:100 region of LC-247 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANSFPITFGQGTRLEIK

HC-248 DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE

GAFDIWGQGTLVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWY NO:101 region of LC-248 QQKPGKAPKLLIYDASTLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPLTFGQGTRLEIK

HC-249 DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE

GAFDIWGQGTLVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWY NO:102 region of LC-249 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPLTFGQGTRLEIK

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:143 variable region of WVRQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTI

Ab 85 SADKSISTAYLQWSSLKASDTAMYYCARHGRGYEG

YEGAFDIWGQGTLVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRSSQGIRSDLGWY NO:144 region of Ab 85 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIK

SEQ ID Ab85 CDR-H1 NYWIG

NO:145

SEQ ID Ab85 CDR-H2 IINPRDSDTRYRPSFQG

NO:146

SEQ ID Ab85 CDR-H3 HGRGYEGYEGAFDI

NO:147

SEQ ID Ab85 CDR-L1 RSSQGIRSDLG

NO:148

SEQ ID Ab85 CDR-L2 DASNLET

NO:149

SEQ ID Ab85 CDR-L3 QQANGFPLT

NO:150

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG N0:151 variable region of WVRQMPGKGLEWMGIIYPGDSDIRYSPSLQGQVTIS

Ab 86 VDTSTSTAYLQWNSLKPSDTAMYYCARHGRGYNGY

EGAFDIWGQGTLVTVSS Sequence Description Amino Acid Sequence

Identifier

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGDSLAWY NO:152 region of Ab 86 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK

SEQ ID Ab86 CDR-H1 NYWIG

NO:145

SEQ ID Ab86 CDR-H2 IIYPGDSDIRYSPSLQG

NO:153

SEQ ID N0:3 Ab86 CDR-H3 HGRGYNGYEGAFDI

SEQ ID Ab86 CDR-L1 RASQGIGDSLA

NO:154

SEQ ID Ab86 CDR-L2 DASNLET

NO:149

SEQ ID Ab86 CDR-L3 QQLNGYPIT

NO:155

Ab 87 SADKSISTAYLQWSSLKASDTAMYYCARHGRGYEG

YEGAFDIWGQGTLVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:156 region of Ab 87 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK

SEQ ID Ab87 CDR-H1 NYWIG

NO:145

SEQ ID Ab87 CDR-H2 IINPRDSDTRYRPSFQG

NO:146

SEQ ID Ab87 CDR-H3 HGRGYEGYEGAFDI

NO:147

SEQ ID Ab87 CDR-L1 RASQGIRNDLG

NO:157

SEQ ID N0:5 Ab87 CDR-L2 DASSLES

SEQ ID Ab87 CDR-L3 QQLNGYPIT

NO:155 Sequence Description Amino Acid Sequence

Identifier

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:158 variable region of WVRQMPGKGLEWMGIIYPGDSLTRYSPSFQGQVTI

Ab 88 SADKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTLVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWY NO:156 region of Ab 88 QQKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK

SEQ ID Ab88 CDR-H1 NYWIG

NO:145

SEQ ID Ab88 CDR-H2 IIYPGDSLTRYSPSFQG

NO:159

SEQ ID N0:3 Ab88 CDR-H3 HGRGYNGYEGAFDI

SEQ ID Ab88 CDR-L1 RASQGIRNDLG

NO:157

SEQ ID N0:5 Ab88 CDR-L2 DASSLES

SEQ ID Ab88 CDR-L3 QQLNGYPIT

NO:155

SEQ ID Heavy chain EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:160 variable region of WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI

Ab89 SADKSISTAYLQWSSLKASDTAMYYCARHGRGYNG

YEGAFDIWGQGTLVTVSS

SEQ ID Light chain variable DIQMTQSPSSLSASVGDRVTITCRASQGIGDSLAWY NO:152 region of Ab89 QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT

LTISSLQPEDFATYYCQQLNGYPITFGQGTKVEIK

SEQ ID Ab89 CDR-H1 NYWIG

NO:145

SEQ ID N0:2 Ab89 CDR-H2 IIYPGDSDTRYSPSFQG

SEQ ID N0:3 Ab89 CDR-H3 HGRGYNGYEGAFDI

SEQ ID Ab89 CDR-L1 RASQGIGDSLA

NO:154

SEQ ID Ab89 CDR-L2 DASNLET

NO:149

SEQ ID Ab89 CDR-L3 QQLNGYPIT

NO:155 Sequence Description Amino Acid Sequence

Identifier

SEQ ID NO: Heavy chain QVQLVQSGAAVKKPGESLKISCKGSGYRFTSYWIG 161 variable region WVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTI amino acid SAGKSISTAYLQWSSLKASDTAMYYCARHGRGYNG sequence of CK6 YEGAFDIWGQGTMVTVSS

SEQ ID NO: Light chain variable AIQLTQSPSSLSASVGDRVTITCRASQGISSALAWYQ 162 region amino acid QKPGKAPKLLIYDASSLESGVPSRFSGSGSGTDFTL sequence of CK6 TISSLQPEDFATYYCQQFNSYPLTFGGGTKVEIK

SEQ ID Ab77 CDR-H1 TYWIG

NO:163

SEQ ID NO:2 Ab77 CDR-H2 IIYPGDSDTRYSPSFQG

SEQ ID NO:3 Ab77 CDR-H3 HGRGYNGYEGAFDI

SEQ ID Ab77 CDR-L1 RASQGVISALA

NO:164

SEQ ID Ab77 CDR-L2 DASILES

NO:165

SEQ ID Ab77 CDR-L3 QQFNSYPLT

NO:166

SEQ ID Ab79 CDR-H1 TYWIG

NO:163

SEQ ID NO:2 Ab79 CDR-H2 IIYPGDSDTRYSPSFQG

SEQ ID NO:3 Ab79 CDR-H3 HGRGYNGYEGAFDI

SEQ ID Ab79 CDR-L1 RASQGVGSALA

NO:167

SEQ ID Ab79 CDR-L2 DASILES

NO:165

SEQ ID Ab79 CDR-L3 QQFNSYPLT

NO:166

SEQ ID Ab81 CDR-H1 TYWIG

NO:163

SEQ ID NO:2 Ab81 CDR-H2 IIYPGDSDTRYSPSFQG

SEQ ID NO:3 Ab81 CDR-H3 HGRGYNGYEGAFDI

SEQ ID Ab81 CDR-L1 RASQGVISALA

NO:164

SEQ ID Ab81 CDR-L2 DASTLES

NO:168 Sequence Description Amino Acid Sequence

Identifier

SEQ ID Ab81 CDR-L3 QQFNSYPLT

NO:166

SEQ ID Heavy chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP NO:169 constant region VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP

(Wild type (WT)) SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT

CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTC

VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

SEQ ID Heavy chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP NO:170 constant region VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP with L234A, L235A SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT (LALA) mutations CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC (mutations in bold)^* VVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY

NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KSLSLSPGK

SEQ ID Heavy chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP N0:171 constant region VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP with D265C SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT mutation CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

(mutation in bold)^* VVCVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV

KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKS

LSLSPGK Sequence Description Amino Acid Sequence

Identifier

SEQ ID Heavy chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP NO:172 constant region VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP with H435A SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT mutation CPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCV

(mutation in bold)^* VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN

STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE

KTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLV

KGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF

LYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQKS

LSLSPGK

SEQ ID Heavy chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP NO:173 constant region: VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP modified Fc region SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT with L234A, L235A, CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC D265C mutations VVVCVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY (mutations in bold)^* NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ

KS LSLSPGK

SEQ ID Heavy chain ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEP NO:174 constant region: VTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVP modified Fc region SSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHT with L234A, L235A, CPPCPAPEAAGGPSVFLFPPKPKDTLMISRTPEVTC D265C, H435A VVVCVSHEDPEVKFNWYVDGVEVHNAKTKPREEQY mutations NSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI

(mutations in bold)^* EKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCL

VKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGS

FFLYSKLTVDKSRWQQGNVFSCSVMHEALHNAYTQ

KS LSLSPGK Sequence Description Amino Acid Sequence

Identifier

SEQ ID Ab85 full length EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:175 heavy chain WVRQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTI sequence; constant SADKSISTAYLQWSSLKASDTAMYYCARHGRGYEG region underlined YEGAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKST

SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF

PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFL

FPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY

VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDW

LNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQ

PENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN

VFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID Ab85 full length EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:176 heavy chain WVRQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTI sequence; constant SADKSISTAYLQWSSLKASDTAMYYCARHGRGYEG region underlined; YEGAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKST modified Fc region SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF with L234A, L235A PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP mutations SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF

(mutations in bold)^* LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNW

YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD

WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN

GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGK

Sequence Description Amino Acid Sequence

Identifier

SEQ ID Ab85 full length EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:177 heavy chain WVRQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTI sequence: constant SADKSISTAYLQWSSLKASDTAMYYCARHGRGYEG region underlined; YEGAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKST modified Fc region SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF with L234A, L235A, PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP D265C mutations SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF (mutations in bold)^* LFPPKPKDTLMISRTPEVTCVVVCVSHEDPEVKFNW

YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD

WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN

GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNHYTQKSLSLSPGK

SEQ ID Ab85 full length EVQLVQSGAEVKKPGESLKISCKGSGYSFTNYWIG NO:178 heavy chain WVRQMPGKGLEWMAIINPRDSDTRYRPSFQGQVTI sequence (LALA - SADKSISTAYLQWSSLKASDTAMYYCARHGRGYEG D265C - H435A YEGAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKST mutant); constant SGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTF region underlined PAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKP

SNTKVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVF

LFPPKPKDTLMISRTPEVTCVVVCVSHEDPEVKFNW

YVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQD

WLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV

YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESN

GQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQ

GNVFSCSVMHEALHNAYTQKSLSLSPGK

Sequence Description Amino Acid Sequence

Identifier

SEQ ID Ab249 full length EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGW NO:179 heavy chain VRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISA sequence; constant DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE region underlined GAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG

GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT

KVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPP

KPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDG

VEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNG

KEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPP

SRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPEN

NYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFS

CSVMHEALHNHYTQKSLSLSPGK

SEQ ID Ab249 full length EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGW NO:180 heavy chain VRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISA sequence; constant DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE region underlined GAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG (LALA mutations)^* GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV

LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT

KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP

PKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD

GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

Sequence Description Amino Acid Sequence

Identifier

SEQ ID Ab249 full length EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGW N0:181 heavy chain VRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISA sequence; constant DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE region underlined GAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG (LALA - D265C GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV mutations)^* LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT

KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP

PKPKDTLMISRTPEVTCVVVCVSHEDPEVKFNWYVD

GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNHYTQKSLSLSPGK

SEQ ID Ab249 full length EVQLVQSGAEVKKPGESLKISCKGSGYRFTTSWIGW NO:182 heavy chain VRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISA sequence; constant DKSISTAYLQWSSLKASDTAMYYCARHGLGYNGYE region underlined; GAFDIWGQGTLVTVSSASTKGPSVFPLAPSSKSTSG (LALA - D265C - GTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV H435A mutations)^* LQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNT

KVDKKVEPKSCDKTHTCPPCPAPEAAGGPSVFLFP

PKPKDTLMISRTPEVTCVVVCVSHEDPEVKFNWYVD

GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN

GKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLP

PSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPE

NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVF

SCSVMHEALHNAYTQKSLSLSPGK

SEQ ID Light chain RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREA NO:183 constant region KVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTL

TLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

SEQ ID Ab85 full length DIQMTQSPSSLSASVGDRVTITCRSSQGIRSDLGWY NO:184 light chain; QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT constant region LTISSLQPEDFATYYCQQANGFPLTFGGGTKVEIKRT underlined VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV

QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL

SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC Sequence Description Amino Acid Sequence

Identifier

SEQ ID Ab249 light chain; DIQMTQSPSSLSASVGDRVTITCRASQGIGSALAWY NO:185 constant region QQKPGKAPKLLIYDASNLETGVPSRFSGSGSGTDFT underlined LTISSLQPEDFATYYCQQLNGYPLTFGQGTRLEIKRT

VAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV

QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTL

SKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

SEQ ID Ab249 HC-CDR1 TSWIG

NO:186

SEQ ID N0:2 Ab249 HC-CDR2 IIYPGDSDTRYSPSFQG

SEQ ID Ab249 HC-CDR3 HGLGYNGYEGAFDI

NO:187

SEQ ID Ab249 LC-CDR1 RASQGIGSALA

NO:188

SEQ ID Ab249 LC-CDR2 DASNLET

NO:149

SEQ ID Ab249 LC-CDR3 CQQLNGYPLT

NO:189

Other Embodiments

All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the same extent as if each independent publication or patent application was specifically and individually indicated to be incorporated by reference.

While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the invention that come within known or customary practice within the art to which the invention pertains and may be applied to the essential features hereinbefore set forth, and follows in the scope of the claims.

Other embodiments are within the claims.

Claims

CLAIMS What is claimed is:

1 . An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 145, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:146, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 147; and comprising a light chain variable region comprising a CDR1 comprising the amino acid sequence as set forth in SEQ ID NO: 148, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO:149, and a CDR3 comprising the amino acid sequence as set forth in SEQ ID NO: 150.

2. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 143, and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 144.

3. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:153, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 154, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

4. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 151 , and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 152.

5. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:146, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 147; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 157, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

6. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 143, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 156.

7. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:159, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 157, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:5, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

8. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 158, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 156.

9. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 145, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 154, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 155.

10. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 160, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 152.

1 1 . An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 99.

12. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 99.

13. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 100.

14. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 101 .

15. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 186, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 187; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 188, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:149, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 189.

16. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 98, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 102.

17. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 99.

18. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 163, a CDR2 domain comprising the amino acid sequence as set forth in

SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 164, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:168, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 166.

19. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 95.

20. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 163, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 167, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:165, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 166.

21 . An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 93.

22. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 163, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:2, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 3; and comprising a light chain variable region comprising a CDR1 domain comprising the amino acid sequence as set forth in SEQ ID NO: 164, a CDR2 domain comprising the amino acid sequence as set forth in SEQ ID NO:165, and a CDR3 domain comprising the amino acid sequence as set forth in SEQ ID NO: 166.

23. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 7, and a light chain variable region comprising the amino acid sequence as set forth in SEQ ID NO: 91 .

24. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain comprising the heavy chain CDR sets (CDR1 , CDR2, and CDR3) forth in the heavy chain amino acid sequences described in Table 1 , Table 5 or Table 7, and a light chain comprising the heavy chain CDR sets (CDR1 , CDR2, and CDR3) forth in the light chain amino acid sequences described in Table 1 , Table 5 or Table 7.

25. An isolated anti-CD1 17 antibody, or antigen-binding fragment thereof, comprising a heavy chain variable region as forth in Table 1 , Table 5 or Table 7, and a light chain comprising the light chain variable region as forth in Table 1 , Table 5 or Table 7.

26. The anti-CD1 17 antibody, or antigen binding fragment thereof, of any one of claims 1 - 25, wherein the antibody, or antigen binding fragment, has a dissociation rate (k_dis) of 1 x 10^"2 to 1 x 10^"3, 1 x 10^"3 to 1 x 10^"4, 1 x 10^"5 to 1 x 10^"6, 1 x 10^"6 to 1 x 10^"7 or 1 x 10^"7 to 1 x 10^"8as measured by bio-layer interferometry (BLI).

27. The anti-CD1 17 antibody, or antigen binding fragment thereof, of any one of claims 1 - 25, wherein the antibody, or antigen binding fragment, binds CD1 17 with a K_D of about 100 nM or less, about 90nM or less, about 80 nM or less, about 70 nM or less, about 60 nM or less, about 50 nM or less, about 40 nM or less, about 30 nM or less, about 20 nM or less, about 10 nM or less, about 8 nM or less, about 6 nM or less, about 4 nM or less, about 2 nM or less, about 1 nM or less as determined by a Bio-Layer Interferometry (BLI) assay.

28. The anti-CD1 17 antibody, or antigen binding fragment thereof, of any one of claims 1 -

27, wherein the antibody, or antigen-binding fragment thereof, is human.

29. The anti-CD1 17 antibody, or antigen binding fragment thereof, of any one of claims 1 -

28, wherein the antibody is an intact antibody.

30. The anti-CD1 17 antibody or antigen-binding fragment thereof of any one of claims 1 -

29, wherein the antibody is an IgG.

31 . The anti-CD1 17 antibody or antigen-binding fragment thereof, of claim 30, wherein the IgG is an lgG1 or an lgG4.

32. The anti-CD1 17 antibody or antigen-binding fragment thereof, of any one of claims 1 - 31 , wherein the antibody or antigen-binding fragment thereof is a monoclonal antibody.

33. The anti-CD1 17 antibody or antigen-binding fragment thereof, of any one of claims 1 - 31 , comprising a heavy chain constant region having an amino acid sequence as set forth as SEQ ID NO: 169 and/or a light chain constant region comprising an amino acid sequence as set forth in SEQ ID NO: 183.

34. The anti-CD1 17 antibody or antigen-binding fragment thereof, of any one of claims 1 - 33, comprising an Fc region comprising at least one amino acid substitution selected from the group consisting of D265C, H435A, L234AA, and L235A (numbering according to the EU index).

35. The anti-CD1 17 antibody or antigen-binding fragment thereof, of claim 34, wherein the Fc region comprises amino acid substitutions D265C, L234A, and L235A (numbering according to the EU index).

36. An intact anti-CD1 17 human antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 184, and a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 175, SEQ ID NO: 176, SEQ ID NO: 177, and SEQ ID NO: 178.

37. An intact anti-CD1 17 human antibody comprising a light chain comprising an amino acid sequence as set forth in SEQ ID NO: 185, and a heavy chain comprising an amino acid sequence selected from the group consisting of SEQ ID NO 179, SEQ ID NO: 180, SEQ ID NO: 181 , and SEQ ID NO: 182.

38. A method of depleting a population of CD1 17+ cells in a human patient comprising administering the antibody of any one of claims 1 -37 to the human patient.

39. The method of claim 38, wherein the human patient is in need of a hematopoietic stem cell transplant.

40. A method of treating a human subject having a hematological cancer comprising administering the anti-CD1 17, or antigen binding fragment thereof, of any one of claims 1 -37 to the human subject having the hematological cancer.

41 . The method of claim 40, wherein the hematological cancer is leukemia.

42. A pharmaceutical composition comprising the antibody, or antigen-binding portion thereof, of any one of claims 1 -37, and a pharmaceutically acceptable carrier.