ANTI-CD79B ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND PHARMACEUTICAL USE THEREOF

Abstract

The present invention relates to an anti-CD79B antibody, an antigen-binding fragment thereof, and its pharmaceutical use. Furthermore, the present invention relates to a chimeric antibody and a humanized antibody comprising a CDR region of the anti-CD79B antibody, a pharmaceutical composition comprising the anti-CD79B antibody or its antigen-binding fragment, and its use as an anti-CD79B cancer drug. In particular, the present invention relates to a humanized anti-CD79B antibody and its use in the preparation of a drug for the treatment of lymphoma (such as DLBCL).

Description

ANTI-CD79B ANTIBODY, ANTIGEN-BINDING FRAGMENT THEREOF AND USE PHARMACIST OF THE SAME nQ / onn / Lznz / e / YiAi This application claims priority of the Chinese patent application Anti-CD79B Antibody, an antigen-binding fragment thereof and pharmaceutical use thereof (application number 201910083330.4) filed on January 28, 2019, which is incorporated herein by reference. Field of Invention The present invention relates to a human anti-CD79B antibody and an antigen-binding fragment, a chimeric antibody and a humanized antibody comprising the CDR region or regions of the anti-CD79B antibody, a pharmaceutical composition comprising the human anti-CD79B antibody or the antigen-binding fragment thereof, and its use as a cancer drug, in particular as a drug for the treatment of lymphoma (DLBCL). Background of the Invention Malignant tumors (cancer) are the second leading cause of death worldwide, after heart disease. Lymphoma is a malignant tumor that originates in the lymphoid hematopoietic system and is the most common hematological tumor globally. The incidence of lymphoma in China has increased in recent years, and the current incidence is approximately 6.68 cases per 100,000 people. Lymphoma is divided into two types: non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL). Non-Hodgkin lymphoma is a general term for a group of diseases characterized by the abnormal proliferation of lymphocytes, exhibiting significant heterogeneity. Its incidence is much higher than that of Hodgkin lymphoma, accounting for more than 80% of all lymphomas. Among these, diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma in adults, representing approximately 32.5% of all non-Hodgkin lymphomas; in the Asian population, this proportion is even higher, approaching 40%. It is more common in older patients, with a median age of onset of 60 to 64 years. There are slightly more male patients than female patients. Currently, the standard first-line regimen for diffuse large B-cell lymphoma (DLBCL) is rituximab combined with chemotherapy (R-CHOP). Before rituximab became available, the anthracycline-based CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) was the standard first-line treatment for DLBCL. The R-CHOP treatment regimen has significantly improved the long-term survival rate for patients with DLBCL. Clinical trial results show that, compared to the traditional CHOP regimen, the R-CHOP regimen can significantly prolong the median overall survival time for patients with DLBCL by 4.9 years, the median disease-free survival time by more than 6.6 years, and the 5-year disease-free survival rate has increased from 30% to 54%.However, 10% to 15% of refractory patients still do not respond, and 20% to 30% relapse. Furthermore, not all patients with DLBCL are suitable for the R-CHOP regimen, such as elderly patients over 80 years of age whose physical condition does not allow for standard R-CHOP treatment. Another example is that the R-CHOP regimen may not be appropriate for more aggressive types of lymphoma and relapsed lymphoma. Therefore, it is extremely important to develop a new generation of immunotherapies with fewer side effects for the treatment of DLBCL. According to the classification of lymphocytes by origin, diffuse large B-cell lymphoma (DLBCL) belongs to the B-cell lymphoma group. The B-cell receptor complex (BCR) is the most important molecule on the surface of B cells. The BCR complex consists of membrane immunoglobulin (IgI), which recognizes and binds to antigen, and the IgA (CD79a) and IgP (CD79b) heterodimers, which transmit antigenic stimulation signals. IgA and IgP are glycoproteins of 47 kDa and 37 kDa, respectively, and belong to the immunoglobulin superfamily. The genes encoding IgA and IgP are designated mb-1 and B29, respectively. Both IgA and IgP have an Ig-like domain at the amino terminus of their extracellular region. Both IgA and IgP can be used as substrates for protein tyrosine kinases and participate in BCR signal transduction. The BCR is widely expressed in B-cell lymphomas and normal B cells.Given the clinical success and reliable safety of rituximab targeting CD20, the development of therapeutic methods targeting BCR should also have a good curative effect and safety. In response to unmet medical needs related to CD79B, many international pharmaceutical companies, including Roche Pharmaceuticals, are actively developing nQ / onn / Lznz / e / YiAi antibodies against CD79B and related products. Related patents include US9085630, W02009012256, WO2009012268, WO2009099728, WO2014011519, WO2014011521, WO2016090210, WO2016205176, W02016040856, W02016021621, WO2017009474, WO2014177615, and others. Based on CD79B expression, generating therapeutic antibodies against the CD79B antigen is beneficial. There is still an unmet need in the technique for developing effective human anti-CD79B antibodies to treat hematopoietic tumors or slow their progression. nQ / onn / Lznz / e / YiAi Summary of the Invention The present invention provides an anti-CD79B antibody or an antigen-binding fragment thereof, a nucleic acid encoding it, a vector, a host cell, an antibody-drug conjugate and a pharmaceutical composition thereof, and a method using it to treat or delay cancer, especially hematopoietic tumors. In the first aspect, the present invention provides a human anti-CD79B antibody or an antigen-binding fragment thereof, comprising an antibody heavy chain variable region and an antibody light chain variable region, wherein: The variable region of the antibody heavy chain comprises at least one complementarity-determining region (HCDR) as shown in the sequences selected from the following: SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25; and / or the variable region of an antibody light chain comprises at least one complementarity-determining region (LCDR) as shown in the sequences selected from the following: SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 16 and SEQ ID NO: 26. In some forms, a human anti-CD79B antibody or an antigen-binding fragment thereof is provided, where: The variable region of the heavy chain comprises: (I) HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively; or (II) HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15, respectively; or (III) HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25, respectively; and / or the variable region of the light chain comprises: (I) LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; or (II) LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 16, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; or (III) LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 26, SEQ ID NO: 11 and SEQ ID NO: 12, respectively. In some specific modalities, a human anti-CD79B antibody or an antigen-binding fragment thereof is provided, comprising any selected from the following (I) to (III): (I) a heavy chain variable region, comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively; and a light chain variable region, comprising LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; (II) a heavy chain variable region, comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15, respectively; and a light chain variable region, comprising LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 16, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; (III) a heavy chain variable region, comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25, respectively; and a light chain variable region, comprising LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 26, SEQ ID NO: 11 and SEQ ID NO: 12, respectively. In some specific modalities, a human anti-CD79B antibody or an antigen-binding fragment thereof is provided, wherein: the variable region of the heavy chain comprises: (I) the sequence as shown in SEQ ID NO: 3 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 3; or (II) the sequence as shown in SEQ ID NO: 5 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 5; or nQ / onn / Lznz / e / YiAi (III) the sequence as shown in SEQ ID NO: 17 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 17; and / or the variable region of the light chain comprises: (I) the sequence as shown in SEQ ID NO: 4 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 4; or (II) the sequence as shown in SEQ ID NO: 6 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 6; or (III) the sequence as shown in SEQ ID NO: 18 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 18. In some specific modalities, the heavy chain variable region of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 3, and the light chain variable region is as shown in SEQ ID NO: 4. In some other specific modalities, the heavy chain variable region of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 5, and the light chain variable region is as shown in SEQ ID NO: 6. In some other specific modalities, the heavy chain variable region of the anti-human CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 17, and the light chain variable region is as shown in SEQ ID NO: 18. In some specific modalities, the human anti-CD79B antibody or its antigen-binding fragment, where: The heavy chain comprises: (I) the sequence as shown in SEQ ID NO: 19 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 19; or (II) the sequence as shown in SEQ ID NO: 21 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 21; and / or the light chain comprises: (I) the sequence as shown in SEQ ID NO: 20 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 20; or nQ / onn / Lznz / e / YiAi (II) the sequence as shown in SEQ ID NO: 22 or the sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 22; In some specific modalities, the heavy chain of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 19, and the light chain is as shown in SEQ ID NO: 20. In some other specific modalities, the heavy chain of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 21, and the light chain is as shown in SEQ ID NO: 22. In some modalities, the human anti-CD79B antibody or its antigen-binding fragment, as described above, is provided, which is a murine antibody or a fragment thereof. In some specific modalities, the variable light chain region of the murine anti-CD79B antibody or its antigen-binding fragment comprises the FR light chain region and / or the constant light chain region of the murine κ, λ chain or a variant thereof. In some specific modalities, the murine anti-CD79B antibody or its antigen-binding fragment comprises the FR heavy chain region and / or the constant heavy chain region of murine IgG1, IgG2, IgG3, IgG4 or a variant thereof. In some embodiments, the human anti-CD79B antibody or an antigen-binding fragment thereof, as described above, is provided, which is a chimeric antibody or a fragment thereof. In some specific embodiments, the chimeric anti-CD79B antibody or its antigen-binding fragment comprises the FR light chain region and / or the constant light chain region of the human κ, λ chain or a variant thereof, and / or the FR heavy chain region and / or the constant heavy chain region of human IgG1, IgG2, IgG3, IgG4 or a variant thereof. In some modalities, the human anti-CD79B antibody or its antigen-binding fragment is provided as described above, which is a humanized antibody, a human antibody, or a fragment thereof. In some embodiments, the humanized anti-human CD7 9B antibody or an antigen-binding fragment thereof is provided as described above, wherein the light chain sequence is shown in SEQ ID NO: 20 or a variant sequence thereof; the variant sequence comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid changes in the light chain, or has at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 20. The heavy chain sequence is shown in SEQ ID NO: 19 or a variant sequence thereof; The variant sequence comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid changes in the heavy chain, or has at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 19. In some embodiments, the humanized anti-human CD79B antibody or antigen-binding fragment thereof is provided as described above, wherein the light chain sequence is shown in SEQ ID NO: 22 or a variant sequence thereof, or has at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% identity with SEQ ID NO: 22; the variant sequence comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acid changes in the light chain. The heavy chain sequence is shown in SEQ ID NO: 21 or a variant sequence thereof; The variant sequence comprises 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 amino acid changes in the heavy chain, or has at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 21. In some formulations, the human anti-CD79B antibody or a fragment thereof, as described above, further comprises the constant region of human IgG1, IgG2, IgG3, or IgG4, or a variant thereof. In some specific formulations, the human anti-CD79B antibody or a fragment thereof comprises the constant region of human IgG1 or IgG2. In some embodiments, the humanized anti-CD79B antibody or fragment thereof as described above, further comprising the human IgG1, IgG2, IgG3 or IgG4 heavy chain constant region or a variant thereof, preferably comprising the human IqG1, IgG2 or IgG4 heavy chain FR region, more preferably comprising the human IgG1 or IgG2 heavy chain FR region. In some modalities, the human anti-CD79B antibody or its antigen-binding fragment as described above, wherein the antigen-binding fragment is selected from the group consisting of Fab, Fv, sFv, F(ab')2, linear antibody, single-chain antibody, scFv, sdAb, sdFv, nanobody, peptibody, domain antibody, and multispecific antibody (bispecific antibody, dibody, tribody, tetrabody, tandem di-scFv, and tandem tri-scFv). nQ / onn / Lznz / e / YiAi In some modalities, an isolated monoclonal antibody or an antigen-binding fragment thereof is provided, which can compete with the aforementioned monoclonal antibody or an antigen-binding fragment thereof for binding to human CD79B or its epitope. The amino acid residues of the CDR VH / VL of the human anti-CD79B antibody in the present invention are determined and annotated using the Chothia numbering system. In the second aspect, the present invention provides a polynucleotide encoding the human anti-CD79B antibody or its antigen-binding fragment as described above, which may be DNA or RNA. In the third aspect, the present invention provides an expression vector comprising the polynucleotide as described above, which may be a eukaryotic expression vector, a prokaryotic expression vector, or a viral vector. In a fourth aspect, the present invention provides a host cell transformed with the expression vector as described above, which can be a eukaryotic cell or a prokaryotic cell. In some forms, the host cell is a bacterium, yeast, or mammalian cell. In some specific forms, the host cell is Escherichia solium, Pichia pastoria, a Chinese hamster ovary cell (CHO), or a human embryonic kidney cell (HEK). In a fifth aspect, the present invention provides an antibody-drug conjugate. The antibody-drug conjugate according to the present invention comprises or consists of the following: antibody, linker, and drug. In one specific embodiment, the antibody-drug conjugate according to the present invention is an antibody covalently coupled to a drug through a linker. In some formulations, the antibody-drug conjugate contains a cytotoxic agent. In some specific formulations, the cytotoxic agent is selected from the group consisting of a toxin, chemotherapeutic agent, antibiotic, radioisotope, and nucleolytic enzyme. In the sixth aspect, the present invention provides a method for preparing the human anti-CD79B antibody or antigen-binding fragment thereof, comprising: expressing the antibody or antigen-binding fragment thereof in the host cell as described above, and isolating the antibody or antigen-binding fragment thereof from the host cell. In the seventh aspect, the present invention provides a composition, for example a pharmaceutical composition, containing a therapeutically effective amount of the aforementioned human anti-CD79B antibody or antigen-binding fragment thereof and a pharmaceutically acceptable excipient, diluent or vehicle. In some specific embodiments, the unit dose of the pharmaceutical composition comprises from 0.01% to 99% by weight of the human anti-CD79B antibody or antigen-binding fragment thereof, or the amount of the anti-CD79B antibody or antigen-binding fragment thereof in the unit dose of the pharmaceutical composition is from 0.1 mg to 2000 mg and, in some specific embodiments, from 1 mg to 1000 mg. In the eighth aspect, the present invention further provides for the use of any or a selected combination of the following in the preparation of a medicament: the human anti-CD79B antibody or antigen-binding fragment thereof according to the present invention, the pharmaceutical composition according to the present invention, and the antibody-drug conjugate according to the present invention; wherein the medicament or the pharmaceutical composition is used to treat a proliferative disease or to delay the progression of a proliferative disease; said proliferative disease may be cancer or a tumor. In some instances, the cancer or tumor is lymphoma or leukemia. In one specific instance, the lymphoma is selected from the group consisting of diffuse large B-cell lymphoma, non-Hodgkin lymphoma, small lymphocytic lymphoma, and mantle cell lymphoma.In one specific modality, non-Hodgkin lymphoma is selected from the group consisting of aggressive NHL, relapsed aggressive NHL, relapsed painless NHL, refractory NHL, and refractory painless NHL. In one specific modality, leukemia is selected from the group consisting of chronic lymphocytic leukemia, hairy cell leukemia, and acute lymphocytic leukemia. In the ninth aspect, the present invention further provides a method for treating or preventing a proliferative disease or for delaying the progression of a proliferative disease, comprising administering to a subject a therapeutically effective or disease-delaying amount of the anti-human CD79B antibody or antigen-binding fragment thereof according to the present invention, or the pharmaceutical composition according to the present invention, or the antibody-drug conjugate according to the present invention; wherein the proliferative disease may be cancer or a tumor. In some embodiments, the cancer or tumor is lymphoma or leukemia. In one specific embodiment, the lymphoma is selected from the group consisting of diffuse large B-cell lymphoma, non-Hodgkin lymphoma, small lymphocytic lymphoma, and mantle cell lymphoma.In one specific modality, non-Hodgkin lymphoma is selected from the group consisting of aggressive NHL, relapsed aggressive NHL, relapsed painless NHL, refractory NHL, and refractory painless NHL. In one specific modality, leukemia is selected from the group consisting of chronic lymphocytic leukemia, hairy cell leukemia, and acute lymphocytic leukemia. nQ / onn / Lznz / e / YiAi Brief Description of the Figures Figure 1: ELISA detection results of the serum titer in Balb / c mice immunized with human CD79B ECD-hFc protein. Figure 2: FACS detection results of serum titer in Balb / c mice immunized with human CD79B ECD-hFc protein. Figure 3: ELISA detection results of the serum titer in SJL mice immunized with human CD79B ECD-hFc protein. Figure 4: FACS detection results of serum titer in SJL mice immunized with human CD79B ECD-hFc protein. Figure 5: ELISA detection results of the serum titer in SJL mice immunized with human CD79B ECD-his protein. Figure 6: FACS detection results of serum titer in SJL mice immunized with human CD79B ECD-his protein. Figure 7: ELISA detection results of murine anti-human CD79B monoclonal antibodies, in which hlgGl is a negative control antibody and SN8 is a positive control antibody. Figure 8: FACS detection results of murine anti-human CD79B monoclonal antibodies, in which hlgGl is a negative control antibody and SN8 is a positive control antibody. Figure 9: FACS detection results for cross-reactivity of murine anti-human CD79B monoclonal antibodies, wherein mlgG is a negative control antibody; anti-cyno HR008, a murine anti-cyno CD79B monoclonal antibody, whose antibody sequence is derived from the murine anti-cyno CD79B monoclonal antibody (clone number 10D10) in patent WO2009012268A1, is a positive control antibody. nQ / onn / Lznz / e / YiAi Detailed Description of the Invention Conditions To facilitate understanding of the present invention, certain technical and scientific terms are specifically defined below. Unless clearly defined elsewhere in this document, all other technical and scientific terms used herein have the meanings commonly understood by those skilled in the art to which the present invention pertains. The three-letter codes and the one-letter codes of amino acids used in the present invention are as described in J. Biol. Chem, 243, p. 3558 (1968). CD79B refers to any CD79B from any vertebrate source, including mammals such as primates (e.g., humans and macaque monkeys) and rodents (e.g., mice and rats). The term CD79B encompasses full-length, unprocessed CD79B and any form of CD79B processed from cells. The term also encompasses naturally occurring CD79B variants, such as spliced ​​variants, allelic variants, and isoforms. The CD79B polypeptides described herein can be isolated from a variety of sources, such as human tissue types or other sources, or prepared by recombinant or synthetic methods. The term antibody described in the present invention refers to an immunoglobulin, which is a tetrapeptide chain structure composed of two identical heavy chains and two identical light chains linked by interchain disulfide bonds. The amino acid composition and the sequence of the constant region of the immunoglobulin heavy chain differ, resulting in different antigenicity. Accordingly, immunoglobulins can be divided into five types or isotypes: IgM, IgD, IgG, IgA, and IgE. Their corresponding heavy chains are the μ chain, δ chain, γ chain, α chain, and ε chain, respectively. The same type of Ig can be further divided into different subclasses based on differences in the amino acid composition of the hinge region and the number and position of the heavy chain disulfide bonds. For example, IgG can be divided into IgG1, IgG2, IgG3, and IgG4.The light chain is divided into a κ chain or a λ chain based on the difference in the constant region. Each of the five Ig types can have either a κ chain or a λ chain. The sequence of approximately 110 amino acids near the N-terminus of the antibody's heavy and light chains varies considerably and is called the variable region (V region); the remaining amino acid sequence near the C-terminus is relatively stable and is called the constant region (C region). The variable region includes three hypervariable regions (HVRs) and four frame regions (FRs) with relatively conservative sequences. The three hypervariable regions determine the antibody's specificity and are also known as complementarity-determining regions (CDRs). Each light chain variable region (VL) and heavy chain variable region (VH) consists of three CDRs and four FRs. The sequence from the amino-terminus to the carboxy-terminus is FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4.The three CDR regions of the light chain are referred to as LCDR1, LCDR2, and LCDR3; the three CDR regions of the heavy chain are referred to as HCDR1, HCDR2, and HCDR3. The number and position of the CDR amino acid residues in the VL and VH regions of the antibody or antigen-binding fragment follow the known Chothia numbering rules (ABM). The term human antibody or recombinant human antibody includes human antibodies prepared, expressed, created, or isolated by recombinant methods, and the techniques and methods involved are well known in the art, such as: (1) antibodies isolated from transgenic and transchromosomal animals (e.g., mice) of human immunoglobulin genes, or from hybridomas prepared from them; (2) antibodies isolated from host cells (such as transfectionomas) transformed to express the antibodies; (3) antibodies isolated from the recombinant combinatorial human antibody library; and (4) antibodies prepared, expressed, created or isolated by other techniques that are used to splice human immunoglobulin gene sequences into other DNA sequences. These recombinant human antibodies contain variable regions and constant regions, which utilize specific human germline immunoglobulin sequences encoded by germline genes, but also include rearrangements and subsequent nQ / onn / Lznz / e / YiAi mutations such as those that occur during antibody maturation. The term "murine antibody" in the present invention refers to a monoclonal antibody against human CD79B or its epitope, prepared according to current knowledge and skill. During preparation, the test subject is injected with the CD79B antigen or its epitope, and hybridomas expressing antibodies with the desired sequence or functional properties are then isolated. In a specific embodiment of the present invention, the murine anti-CD79B antibody or its antigen-binding fragment may further comprise the constant region of the light chain of the murine κ, λ chain or a variant thereof, or further comprise the constant region of the heavy chain of murine IgG1, IgG2, IgG3, or IgG4 or a variant thereof. The term human antibody includes antibodies having variable and constant regions of human germline immunoglobulin sequences. The human antibodies of the present invention may include amino acid residues that are not encoded by human germline immunoglobulin sequences (such as mutations introduced by random or site-specific mutagenesis in vitro or by somatic mutations in vivo). However, the term human antibody does not include antibodies in which CDR sequences derived from the germline of another mammalian species (such as a mouse) have been grafted onto human scaffold sequences (namely, humanized antibodies). The term humanized antibody, also known as a CDR-grafted antibody, refers to an antibody produced by transplanting CDR sequences from non-human species into the variable regions of human antibodies. It can overcome the strong immune responses induced by chimeric antibodies because it carries a large number of protein components from non-human species. To prevent the decline in activity caused by decreased immunogenicity, the variable region of the human antibody can undergo minimal reverse mutations to maintain activity. The term chimeric antibody refers to an antibody formed by fusing the variable region of an antibody from one species with the constant region of an antibody from a second species. This fusion can mitigate the immune response induced by the antibody of the first species. Establishing a chimeric antibody requires creating a hybridoma that secretes monoclonal antibodies specific to the first species, then cloning the variable region gene from hybridoma cells of the first species (such as a mouse), and then cloning the constant region gene from the antibody of the second species (such as a human). The variable region gene from the first species is then joined with the constant region gene from the second species to form a chimeric gene, which is inserted into an expression vector. Finally, the chimeric antibody molecule is expressed in a eukaryotic or prokaryotic industrial system.The antibody constant region of the second species (e.g., human) can be selected from the group consisting of: the human IgG1, IgG2, IgG3 or IgG4 heavy chain constant region or a variant thereof, preferably comprising the human IgG2 or IgG4 heavy chain constant region or using IgG1 without ADCC (antibody-dependent cell-mediated cytotoxicity) after amino acid mutations. An antigen-binding fragment refers to any fragment that retains the antigen-binding activity of the intact antibody. Specifically, but not limited to, Fab fragments, Fab' fragments, F(ab')2 fragments, and Fv fragments or sFv fragments that bind to human CD79B. The Fv fragment contains the variable region of the antibody's heavy chain and the variable region of its light chain, but lacks the constant region and is the smallest antibody fragment with all antigen-binding sites. Generally, the Fv antibody also contains a linker polypeptide between the VH and VL domains and can form the structure required for antigen binding. Different linkers can also be used to link the two variable regions of the antibody into a single polypeptide chain, which is called a single-stranded antibody or single-stranded Fv (sFv). The term "CD79B binding" in the present invention refers to the ability to interact with CD79B or its epitope. CD79B or its epitope may be of human origin. The term "antigen binding site" in the present invention refers to a linear site or a discontinuous three-dimensional site on the antigen, recognized by the antibody or antigen-binding fragment of the present invention. nQ / onn / Lznz / e / YiAi The term epitope refers to a site on an antigen that specifically binds to an immunoglobulin or antibody. Epitopes can be formed by adjacent amino acids or non-adjacent amino acids brought into close proximity by tertiary folding of the protein. Epitopes formed by adjacent amino acids are generally retained after exposure to a denaturing solvent, while epitopes formed by tertiary folding are generally lost after treatment with a denaturing solvent. Epitopes typically include at least 3–15 amino acids in a unique spatial conformation. Methods for determining which epitope is bound by a given antibody are well-established in the field, including immunoblotting, immunoprecipitation detection assays, and others.Methods for determining the spatial conformation of an epitope include the techniques in the technique and the techniques described in this document, e.g., X-ray crystal analysis, two-dimensional nuclear magnetic resonance, etc. Specific binding and selective binding refer to the binding of an antibody to an epitope on a predetermined antigen. Generally, when recombinant human CD79B or its epitope is used as the analyte and an antibody is used as the ligand, when measured by surface plasmon resonance (SPR) technology in an instrument, the antibody binds to the predetermined antigen or its epitope with a dissociation constant (KD) of approximately below 10⁻⁷ M or even lower, and its binding affinity to the predetermined antigen or its epitope is at least twice the binding affinity to nonspecific antigens (such as BSA, etc.) other than the predetermined antigen (or its epitope) or closely related antigens. Cross-reactivity refers to the ability of the antibodies of the present invention to bind to CD79B from different species. For example, an antibody of the present invention that binds to human CD79B may also bind to CD79B from another species. Cross-reactivity is measured by detecting specific reactivity with purified antigen in binding assays (e.g., SPR and ELISA), or binding to or functional interaction with cells that physiologically express CD79B. Methods for determining cross-reactivity include standard binding assays as described herein, such as surface plasmon resonance analysis or flow cytometry. nQ / onn / Lznz / e / YiAi Inhibition and blockade are used interchangeably and encompass both partial and complete inhibition / blockade. Inhibition / blockade of CD79B preferably reduces or alters the normal level or type of activity that occurs when CD79B binds without inhibition or blockade. Inhibition and blockade are also intended to include any measurable reduction in the binding affinity of CD79B when it comes into contact with the anti-CD79B antibody, compared to CD79B that does not come into contact with the anti-CD79B antibody. Growth inhibition (for example, referring to cells) is intended to include any measurable decrease in cell growth. Methods for producing and purifying antibodies or antigen-binding fragments are well known and can be found in the prior art, such as in Antibody: Laboratory Manual, Coid Spring Harbor (chapters 5-8 and 15). For example, human CD7 9B or a fragment thereof can be used to immunize mice, and the resulting antibodies can be renaturated, purified, and their amino acid sequenced using conventional methods. Antigen-binding fragments can also be prepared using conventional methods. The antibody or antigen-binding fragment of the invention is genetically engineered to introduce one or more human FR regions into non-human CDR regions. Human FR germline sequences can be obtained from the ImmunoGeneTics (IMGT) website http: / / imgt.cines.fr or from The Immunoglobulin FactsBook, 2001 ISBN 012441351. The genetically modified antibodies or antigen-binding fragments of the present invention can be prepared and purified using conventional methods. For example, the cDNA sequences encoding the heavy chain (SEQ ID NO: 20) and the light chain (SEQ ID NO: 21) can be cloned and recombined into a GS expression vector. The recombinant immunoglobulin expression vector can be stably transfected into CHO cells. As a previously recommended technique, mammalian expression systems can lead to antibody glycosylation, particularly at the highly conserved N-terminus of the Fe region. Stable clones are obtained by expressing antibodies that bind specifically to human antigens. Positive clones are expanded in the serum-free medium of the bioreactor to produce antibodies. The culture medium in which the nQ / onn / Lznz / e / YiAi antibodies are secreted can be purified and collected using conventional techniques.Antibodies can be filtered and concentrated using conventional methods. Soluble mixtures and polymers can also be removed using conventional methods, such as molecular sieves and ion exchange. The resulting product should be frozen immediately, for example, at -70°C, or lyophilized. The antibody of the present invention refers to a monoclonal antibody. The monoclonal antibody (mAb) described in the present invention refers to an antibody obtained from a single-clone cell line, which cell line is not limited to a eukaryotic cell line, prokaryotic cell line, or phage clone. Monoclonal antibodies or antigen-binding fragments can be obtained by recombination using, for example, hybridoma technology, recombination technology, phage presentation technology, synthesis technology (such as CDR grafting), or other existing technologies. Conventional techniques known to those skilled in the art can be used to screen antibodies for competitive binding to the same epitope. For example, competition and cross-competition studies can be performed to obtain antibodies that compete with each other for binding to an antigen. A high-throughput method for obtaining antibodies that bind to the same epitope based on their cross-competition is described in International Patent Publication WO03 / 48731. Therefore, conventional techniques known to those skilled in the art can be used to obtain antibodies and antigen-binding fragments thereof that compete with the antibody molecules of the present invention for binding to the same epitope on CD79B. Giving, administering, and treating, when applied to animals, humans, experimental subjects, cells, tissues, organs, or biological fluids, refer to the contact of the exogenous drug, therapeutic agent, diagnostic agent, or composition with the animals, humans, subjects, cells, tissues, organs, or biological fluids. Giving, administering, and treating may refer, for example, to treatment, pharmacokinetics, diagnosis, research, and experimental methods. Cell treatment includes the contact of reagents with cells and the contact of reagents with the fluid that is in contact with the cells. Giving, administering, and treating also refer to treating, for example, cells with reagents, diagnostic reagents, binding compositions, or with another cell in vitro and ex vivo.When applied to human, veterinary, or research subjects, "Treatment" refers to therapeutic treatment, prophylactic treatment or prophylactic measures, research, and diagnostic applications. Treatment refers to administering an internal or external therapeutic agent, such as a composition comprising any of the antibodies or antigen-binding fragments thereof of the present invention, to a subject who already has, is suspected of having, or is susceptible of having one or more diseases or symptoms thereof, and the therapeutic agent is known to have a therapeutic effect on such symptoms. Generally, the therapeutic agent is administered in an amount effective in relieving one or more disease symptoms in the treated subject or population, either to induce the regression of such symptoms or to inhibit the development of such symptoms to any clinically measured degree.The amount of a therapeutic agent that is effective in relieving any specific disease symptom (also called the therapeutically effective amount) can vary depending on a variety of factors, such as the individual's disease status, age, body weight, and the drug's ability to produce the desired therapeutic effect in that individual. Whether disease symptoms have been relieved can be assessed using any clinical testing method that physicians or other healthcare professionals use to evaluate the severity or progression of symptoms.Although the embodiments of the present invention (e.g., treatment methods or products) may be ineffective in relieving the symptom of the target disease in a given subject as determined by any statistical test method known in the art, such as Student's t-test, chi-square test, Mann-Whitney U test, Kruskal-Wallis test (H test), Jonckheere-Terpstra test, and Wilcoxon test, they should reduce the symptom of the target disease in a statistically significant number of subjects. The effective amount includes a quantity sufficient to improve or prevent the symptoms or effects of the medical condition. The effective amount also refers to a quantity sufficient to permit or facilitate diagnosis. The effective amount for a particular individual or veterinary subject may vary depending on the following factors: such as the condition being treated, the subject's general health, the method, route, and dosage of administration, and the severity of side effects. The effective amount may be the maximum dose or dosage schedule that avoids significant side effects or toxicity. Identity refers to the sequence similarity between two polynucleotide sequences or two polypeptides. When positions in the two compared sequences are occupied by the same amino acid monomer subunit or base—for example, if every position in two DNA molecules is occupied by adenine—then the molecules are homologous at that position. The percentage of identity between two sequences is a function of the number of matching or homologous positions shared by the two sequences divided by the total number of positions to be compared (χ 100%). For example, in the case of optimal sequence alignment, if there are 6 matches or homology at 10 positions in the two sequences, then the two sequences are 60% homologous. Generally, comparison is performed when aligning two sequences to obtain the maximum percentage of identity. The terms cell, cell line, and cell culture, as used herein, may be used interchangeably, and all these terms encompass their progeny. Therefore, the terms transformant and transformed cell include primary test cells and cultures derived from them, regardless of the number of passages. It should also be understood that, due to intentional or unintentional mutations, all progeny may not be exactly the same in terms of DNA content. Mutant progeny tested with the same biological function or activity as the original transformed cells are included within the scope of the term. When a term refers to different indications, this would be obvious from the context. Optionally means that the described event or environment following the term optional may occur (but is not necessarily so), and the description includes instances where the event or environment does or does not occur. For example, optionally comprising 1 to 3 antibody heavy chain variable regions means that antibody heavy chain variable regions of specific sequences may be present (but are not necessarily so). nQ / onn / Lznz / e / YiAi Pharmaceutical composition means a mixture comprising one or more of the antibodies or antigen-binding fragments, or conjugates described herein, or a physiologically / pharmaceutically acceptable salt or prodrug thereof, and other chemical component(s), as well as other components such as carriers and physiologically / pharmaceutically acceptable excipients. The purpose of the pharmaceutical composition is to promote delivery to the body, thereby facilitating the absorption of the active ingredient and thus exerting biological activity. nQ / onn / Lznz / e / YiAi Examples The following examples are incorporated to describe the invention in more detail, but these examples do not limit its scope. Experimental methods that do not specify specific conditions in the Examples or Test Examples of the present invention normally follow conventional conditions, or the conditions recommended by the manufacturer of the raw material or product. See Sambrook et al., Molecular Cloning: A Laboratory Manual, Coid, Spring Harbor; Current Protocols in Molecular Biology, Ausubel et al., Greene Publishing Associates, Wiley InterScience, NY. Reagents without specific sources are conventional reagents purchased commercially. Example 1. Cloning and expression of protein antigens The antibodies (comprising light and heavy chains) and antigens were constructed using known overlap extension PCR methods, and the DNA fragments obtained by overlap extension PCR were inserted into the pEE6.4 expression vector (Lonza Biologics) using HindIII / BstBI two-site enzyme cleavage. The antibodies and antigens were then expressed in 293F cells (Invitrogen, Cat # R790-07). The resulting recombinant protein was used for immunization or screening. The human CD79B gene sequence is derived from NCBI (NP 000617.1), and its extracellular region (ECD) contains 159 amino acids (Met1-Aspl59). The amino acid sequence of the human CD79B extracellular domain (ECD) fusion protein and the human FC region (human CD79B ECD-hFc): ARSEDRYRNPKGSACSRIWQSPRFIARKRGFTVKMHCYMNSASGNVSWLWKQEMDENPQQLKLE KGRMEESQNESLATLTIQGIRFEDNGIYFCQQKCNNTSEVYQGCGTELRVMGFSTLAQLKQRNTLKDGII MIQTLLIILFIIVPIFLLLDKDDSKAGMEEDHTYEGLDIDQTATYEDIVTLRTGEVKWSVGEHPGQEEPK SCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAK TKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVM HEALHNHYTQKSLSLSPGK (SEQ ID NO: 1). The amino acid sequence of the extracellular domain (ECD) fusion protein of human CD79B and His tag (ECD-His of human CD79B): ARSEDRYRNPKGSACSRIWQSPRFIARKRGFTVKMHCYMNSASGNVSWLWKQEMDENPQQLKLE KGRMEESQNESLATLTIQGIRFEDNGIYFCQQKCNNTSEVYQGCGTELRVMGFSTLAQLKQRNTLKDGII CONTROL SYSTEMS (SEQ ID NO: 2 ) . nQ / onn / Lznz / e / YiAi Example 2. Preparation of murine monoclonal antibodies 1. Immunization of mice and detection of titer in serum The human CD79B extracellular domain (ECD) fusion protein and the human Fe region (human CD79B ECD-hFc), and the human CD79B extracellular region (ECD) fusion protein and the His tag (human CD79B ECD-His) were used as immunogens to immunize Balb / cy SJL mice by intraperitoneal injection, respectively, to stimulate the mice to produce antibodies against the human CD79B extracellular domain (ECD) in vivo. The experimental steps were as follows: 1) Immunization by intraperitoneal injection. The amount of antigen required for this immunization was calculated according to the immunization procedure. The protein antigen was diluted with PBS to the required antigen concentration, and then emulsified. The emulsified mixture of antigen and adjuvant was transferred to a sterile 2.0 ml syringe, taking care to vent any air bubbles. The mouse's tail was grasped with the right hand, and the skin of the mouse's head and neck was gently grasped with the thumb and forefinger of the left hand. With the abdominal cavity facing upward, the injection site on the right side of the mouse's abdomen was cleaned with a cotton ball soaked in 75% alcohol. The antigen was pre-loaded into the syringe, with the bevel of the needle tip facing upward and the mouse's head facing downward.The needle tip was inserted horizontally into the skin, the syringe was inserted into the mouse's abdominal cavity at a 45-degree angle to the abdominal cavity, and the antigen-adjuvant mixture was slowly injected. Once immunization was complete, the mouse was observed for at least 2 hours. 2) Mouse serum collection. The serum tube number corresponding to each mouse was labeled, and the mouse's pendant number was checked. The mouse was held by hand, and approximately 100 µL of whole blood was collected via the submandibular vein. The collected whole blood sample was allowed to stand at room temperature for approximately 2 h; the serum was then collected from the top of the centrifuge tube by centrifugation. The serum could be stored in a refrigerator at 4°C for up to one week for antibody titer detection and other related experiments. For long-term storage, the serum could be stored in a refrigerator at -80°C to avoid repeated freezing and thawing. 3) Detection of serum titers by ELISA from immunized mice. Before the start of the experiment, a 96-well plate was labeled accordingly and coated with antigen at a concentration of 1 pg / mL, 50 µA per well, overnight in a refrigerator at 4°C. The following day, the coated plate was removed and washed with a plate washer (wash solution: 1 x PBST). After washing, the plate was blocked with a 1% BSA blocking solution prepared in 1 x PBST at 37°C for 1 h. After washing the plate with 1 x PBST wash solution three times, different dilutions of the serum to be tested were added and incubated in an incubator at 37°C for 1 h. After washing the plate with 1 x PBST wash solution 3 times, 100 μA of goat mouse secondary antibody diluted 1:5000 was added and incubated in an incubator at 37°C for 0.5 h.After washing the plate, the chromogenic solutions TMB A and B were mixed in a 1:1 ratio, and then the color development was carried out. The development reaction was stopped with 1 N hydrochloric acid after 15 min. Fluorescence values ​​at 450 nm were detected using a Spectra Max M5 multifunction plate reader. 4) Detection of FACS serum titer from immunized mice. Suspensions of DoHH2 cells or monkey peripheral blood mononuclear cells were centrifuged, and the cells were resuspended in PBS containing 0.1% BSA and counted. Serum to be tested from each group of immunized mice was added. After 60 min of incubation at room temperature, the cells were washed three times, and then an anti-mouse Fc-FITC IgG secondary antibody was added. After 30 min of incubation at room temperature in the dark, the cells were washed three times and gently resuspended in PBS containing 0.1% BSA for detection by the instrument. The results of serum titer detection ELISA and FACS for each group of mice are shown in Figure 1 to Figure 7. Five Balb / c mice, numbered 5491, 5492, 5493, 5494, and 5495, were immunized with human CD79b ECD-hFc protein. The results of the serum ELISA titer detection are shown in Figure 1. The results showed that the serum titer in immunized mice reached over 1:100,000. The results of the FACS detection in mouse serum are shown in Figure 2. It can be seen that the antibodies produced in the mouse serum could specifically recognize the CD79B protein on the surface of DoHH2 cells. Five SJL mice, numbered 5496, 5497, 5498, 5499, and 5500, were immunized with human CD79b ECD-hFc protein. The results of the serum ELISA titer detection are shown in Figure 3. The results showed that the serum titer in immunized mice reached over 1:100K. The results of the FACS detection in mouse serum are shown in Figure 4. It can be seen that the antibodies produced in mouse serum could specifically recognize the CD79B protein on the surface of DoHH2 cells. Five SJL mice, numbered 5726, 5727, 5728, 5729, and 5730, were immunized with human CD79b ECD-his protein. The results of the serum ELISA titer detection are shown in Figure 5. The results showed that the serum titer in immunized mice reached over 1:10K. The results of the FACS detection in mouse serum are shown in Figure 6. It can be seen that the antibodies produced in mouse serum could specifically recognize the CD79B protein on the surface of DoHH2 cells. Based on the above results, it can be determined that the immunized mice produced specific antibodies against CD79B, and the aforementioned mice could be used for cell fusion to generate hybridoma cell lines capable of secreting specific antibodies against CD79B. nQ / onn / Lznz / e / YiAi 2. Preparation of hybridomas and detection of antibodies Cell fusion is spontaneous or artificially induced to promote the fusion of mouse lymphocytes and SP2 / 0 myeloma cells (ATCC, CCL-121TM) into hybridoma cells, which have the function of secreting antibodies and can proliferate indefinitely. Lymphocytes from the immunized mouse group and myeloma cells were fused using the electrofusion method, and the hybridoma cells were used for subsequent antibody selection. 1) Electrofusion experiment. One week prior to fusion, SP2 / 0 cells were expanded in 10% DMEM medium. The spleen and lymph nodes were removed from sacrificed mice in a biological safety cabinet, washed, and ground into Petri dishes, and the lymphocytes were collected. SP2 / 0 cells and lymphocytes were mixed in the correct ratio, fusion was performed using the electrofusion instrument, and the program was run. After fusion, the cells were seeded in a 96-well plate and cultured in a 5% CO2 incubator at 37°C. Cell status was observed daily, and the cell fusion rate was recorded 5 days post-fusion. Fused hybridoma cells were selected 9–14 days post-fusion, and cells from positive wells were selected for expansion in a 24-well plate. 2) Subcloning by limited dilution method. The cell lines to be subcloned were resuspended from 24-well culture plates and counted. Each cell line was diluted to a cell concentration of 5–10 cells / ml. The diluted cell suspension was added to 15 cm disposable culture plates, and 0.2 ml was added to each well of a 96-well culture plate, with each well containing 1–2 cells. The 96-well plate inoculated with the cells was placed in a 5% CO2 incubator at 37°C for culture. After 7–10 days, the subcloning plate was inspected and examined according to the cell growth status. Positive clones were selected and transferred to 24-well plates for further positive confirmation. 3) ELISA Screening. Before the start of the experiment, a 96-well plate was labeled accordingly and coated with an antigen at a concentration of 1 pg / mL, 50 µA per well, overnight in a refrigerator at 4°C. The following day, the coated plate was removed and washed with a plate washer (wash solution nQ / onn / Lznz / e / YiAi: 1 x PBST). After washing, the plate was blocked with a 1% BSA blocking solution prepared in 1 x PBST at 37°C for 1 h. After washing the plate three times with 1 x PBST wash solution, 50 µA of the cell supernatant to be tested was added, and the plate was incubated at 37°C for 1 h. After washing the plate with 1 x PBST wash solution 3 times, 100 μA of goat mouse secondary antibody diluted 1:5000 was added and incubated in an incubator at 37°C for 0.5 h.After washing the plate, the chromogenic solutions TMB A and B were mixed in a 1:1 ratio, and then the color development was carried out. The development reaction was stopped with 1 N hydrochloric acid after 15 min. Fluorescence values ​​at 450 nm were detected using a Spectra Max M5 multifunction plate reader. 4) FACS Screening. DoHH2 cell suspensions were centrifuged, and the cells were resuspended in PBS containing 0.1% BSA and counted. The cell supernatant was added to the assay. After 60 min of incubation at room temperature, the cells were washed three times, and then an anti-mouse Fc-FITC IgG secondary antibody was added. After 30 min of incubation at room temperature in the dark, the cells were washed three times and gently resuspended in PBS containing 0.1% BSA for detection on the instrument. 5) Identification of positive hybridoma clones. After fusion and subclone selection of mouse spleen cells, we obtained a series of antibodies specific against the human CD79B antigen. Among these, 17 hybridomas with the best ELISA and FACS binding capacity were used for antibody production and purification. The ELISA detection results of the cell culture supernatant from anti-human CD79B hybridoma clone-positive cells are shown in Table 1. The FACS detection results of the cell culture supernatant from anti-human CD79B hybridoma clone-positive cells are shown in Table 2. mlgG was used as a negative control in the ELISA and FACS tests. FACS. Table 1. ELISA detection results of human anti-CD79B hybridoma positive clones nQ / onn / Lznz / e / YiAi Antibody Number Cloning Number Detection Results (OD450) Negative Control mlgG 0.05 mAbOOl 12A11-1G1 3.26 mAb002 19F10-1D7 3.69 mAb003 51E5G6 3.02 mAbOO4 67B10C1 3.41 mAb005 78A9F4 3.73 mAbOO 6 48F11D6 3.34 mAb007 61A11F1 3.40 mAbOO8 63G2A2 3.56 mAbOO 9 75F1E2 3.57 mAbOlO 66G3E7 3.83 mAbOll 66E12H3 3.41 mAb012 73A8F3 3.45 mAbO13 74C4F3 3.31 mAb014 70B8B3 3.10 mAb015 83B2G2 3.41 mAbOl6 83C2D4 3.46 mAb017 86F11F6 3.80 Table 2. FACS detection results of anti-CD79B positive human hybridoma clones nQ / onn / Lznz / e / YiAi Antibody number Cloning number Mean fluorescence values ​​Negative control mlgG 58 mAbOOl 12A11-1G1 13032 mAb002 19F10-1D7 5943 mAb003 51E5G6 33918 mAbOO4 67B10C1 26000 mAb005 78A9F4 24454 mAbOO 6 48F11D6 20120 mAb007 61A11F1 18039 mAbOO8 63G2A2 16453 mAbOO 9 75F1E2 16001 mAbOlO 6 6G3E7 15897 mAbOll 66E12H3 14688 mAbO12 73A8F3 14073 mAbO13 74C4F3 12894 mAb014 70B8B3 8776 mAbO15 83B2G2 10036 mAbOl6 83C2D4 9 9 9 0 mAbO17 86F11F6 8132 3. Production, purification and identification of murine monoclonal antibodies 1) Production and purification of murine monoclonal antibodies. Hybridoma cells used for antibody production were observed under a microscope. Cells were harvested when they reached 10 to over 70% cell density and were in good cell condition. They were counted using a Countstar IC1000 cell counter. The cell concentration was adjusted to 1 x 10⁵ to 5 x 10⁵ cells / ml using well-prepared medium, and the cells were transferred to tumblers. The tumblers containing the transferred cells were placed in a tumbler incubator for incubation at 37°C for 10–15 days. The cell growth status was observed daily. The culture was removed for purification after the medium turned orange and clear. The antibodies were purified without passing through the cell supernatant using Protein A columns, following conventional methods. 2) ELISA detection of murine anti-human CD79B monoclonal antibodies. Before the start of the experiment, a 96-well plate was labeled accordingly and coated with an antigen at a concentration of 1 pq / mL, 50 μA per well, overnight in a refrigerator at 4°C. The following day, the previously coated antigen plate was removed and washed once with a plate washer (wash solution: 1 x PBST). After washing, the plate was blocked with a 1% BSA blocking solution prepared in 1 x PBST at 37°C for 1 h. After washing the plate with 1 x PBST wash solution 3 times, 50 μA of antibody, diluted to 100 nM (1:10), were added and incubated in an incubator at 37°C for 1 h. After washing the plate with χ PBST wash solution 3 times, 100 μA of goat mouse secondary antibody diluted 1:5000 was added and incubated in an incubator at 37°C for 0.5 h.After washing the plate, the chromogenic solutions TMB A and B were mixed in a 1:1 ratio, and the color development was carried out. The development reaction was terminated with 1 N hydrochloric acid after 15 min. Fluorescence values ​​at 450 nm were detected using a Spectra Max M5 multifunction plate reader. Among them, three murine anti-human CD79B monoclonal antibodies had the strongest ELISA binding capacity, including mAbO15, mAbO16, and mAbO17 (see Figure 7 for specific data). hlgGl was used as the negative control antibody, and SN8 as the positive control antibody. SN8 is the antibody used in the antibody-conjugated drug polatuzumab vedotin developed by Roche Pharmaceuticals (for the sequence, see sequence source: US20170362318A). Currently, the FDA has approved the marketing of polatuzumab vedotin.It can be seen from the results that in the ELISA experiment, the binding capacity of the three murine anti-human CD79B monoclonal antibodies mAbO15, mAbO16 and mAbO17 preferably selected by the present invention was similar to that of SN8. 3) FACS detection of murine anti-human CD79B monoclonal antibodies. After centrifugation of the DOHH2 cell suspension, the cells were resuspended in PBS containing 0.1% BSA and counted. 100 µA of antibody diluted to 100 nM (1:10) was added, and the cells were incubated for 1 h at room temperature. After washing the cells three times, an anti-mouse Fc-FITC IgG secondary antibody was added. After 30 min of incubation at room temperature in the dark, the cells were washed three times and gently resuspended in PBS containing 0.1% BSA for analysis using an instrument. Among them, three murine anti-human CD79B monoclonal antibodies had the strongest FACS binding capacity, including mAbO15, mAbO16, and mAbO17 (see Figure 8 for specific data). Among these, hlgGl was the negative control antibody and SN8 was the positive control antibody.It can be determined from the results that in the FACS experiment, the binding capacity of the three murine anti-human CD79B monoclonal antibodies mAbO15, mAbO16 and mAbO17 preferably selected by the present invention was better than that of SN8. 4) FACS detection of cross-activity of murine anti-human CD79B monoclonal antibodies. 293F-cynoCD79B cells were obtained by transient transfection. After centrifugation of the cell suspension, the cells were resuspended in PBS containing 0.1% BSA and counted. 100 µA of antibody were added at concentrations of 10 pg / mL and 1 pg / mL, respectively. The cells were incubated for 1 h at room temperature. After washing the cells three times, an anti-mouse Fc-FITC IgG secondary antibody was added. After 30 min of incubation at room temperature in the dark, the cells were washed three times and gently resuspended in PBS containing 0.1% BSA for detection using an instrument.The results of FACS detection showing the cross-activity of murine anti-human CD79B monoclonal antibodies are shown in Figure 9, where mlgGl is a negative control antibody, anti-cyno HR008 is a murine anti-cyno CD79B monoclonal antibody, the antibody sequence from which it is derived from the murine anti-cyno CD7 9B monoclonal antibody (clone number 10D10) in patent WO2 00 9012 2 68 Al. It can be seen from the results that all the murine anti-human CD79B monoclonal antibodies selected in this description did not recognize the cyno CD79B. 5) SPR detection of murine anti-human CD79B monoclonal antibodies. The affinity between the human anti-CD79B antibody and its human CD79B-HIS antigen was detected by surface plasmon resonance (SPR). The human CD79B-HIS antigen protein was immobilized on the nQ / onn / Lznz / e / YiAi chip CMS. The docking level was set at 100 RU. The run buffer was HBS-EP+ (HEPES 10 mM, NaCl 150 mM, EDTA 3 mM, P20 surfactant 0.05%). The diluted antibody was flown through the experimental and control channels at a flow rate of 30 μA / min for 3 min, and dissociation was performed for 5 min. Then, the regenerated buffer (glycine buffer 10 mM, pH 1.5) was run at a flow rate of 30 μA / min for 30 seconds. Data were analyzed using Biacore 8K evaluation software. nQ / onn / Lznz / e / YiAi Example 3. Determination of the amino acid sequence of the variable region of the murine monoclonal antibody The high-affinity hybridoma monoclonal cell lines obtained in Example 2 underwent variable region amino acid sequencing. Human-mouse chimeric antibodies (cAbs) were then recombinantly expressed, and further antibody identification was performed. The heavy and light chain variable regions of the antibody gene were amplified by reverse transcription PCR, attached to a vector, and sequenced to obtain the monoclonal antibody's light and heavy chain sequences. First, total cellular RNA was extracted from the single-cell lines with good activity in Example 2 using an RNA purification kit (Qiagen, item number 74134; see step specification).Next, single-stranded cDNA was prepared using a cDNA synthesis kit (Invitrogen, item number 18080-051), i.e., reverse transcription of the Oligo-dT primer cDNA. This was used as a template to synthesize the variable region sequences of the antibody's light and heavy chains using PCR. The PCR product was cloned into the pMD-18T TA vector and then submitted for sequencing. The resulting antibody light and heavy chain sequences were cloned into an expression vector (see Example 1 for the method), the recombinant monoclonal antibody was expressed, and its activity was verified (see Example 2 for the method). Humanization work was then carried out. The amino acid residues of the CDR VH / VL of the human anti-CD79B antibody in the present invention are determined and annotated using the Chothia numbering system. The heavy chain variable region of the murine hybridoma monoclonal antibody mAbO15: QVQLQQSGAELARPGASVKLSCKASGSSFTSYGINWVKQRTGQGLEWTGETFPRSGNTYYNEKF EGKATLTADKSSSTAYMELRSLTSEDSAVYFCAKGDLGDFDYWGQGTTLTVSS (SEQ ID NO: 3). The light chain variable region of the murine hybridoma monoclonal antibody mAbO15: DFLMTQTPLSLPVRLGDQASISCRSSQSIVHSDGNTYFEWYLQKPGQSPKLLIYKVSNRFSGVP DRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTKLEIK (SEQ ID NO.4) The heavy chain variable region of the murine hybridoma monoclonal antibody mAbO17: QVQLQQSGAELARPGASVKLSCKASGYTFTTYGINWVKQRTGQGLEWIGEIYPRSGNIYYNEKF KGKATLTADKSSSTAYMELRSLTSEDSAVYFCARGSDYDGDFAYWGQGTLVTVSA (SEQ ID NO: 5). The light chain variable region of the murine hybridoma monoclonal antibody mAbO17: DVLMTQTPLSLPVSLGDQASISCRSSQSIVHHDGNTYLEWYLQKPGQSPKLLIYKVSNRFSGVP DRFSGSGSGTDFTLKISRVEAEDLGVYYCFQGSHVPWTFGGGTQLEIK: (SEQ. ID. NO: 6 The heavy chain variable region of the murine hybridoma monoclonal antibody mAbO16: QVQLQQSGAELARPGASVKLSCKASGYIFTNYGIIWVKQRTGQGLEWIGDIFPGSGNTYYNENF KGKATLTADKSSSTAYMELRSLTSEDSAVYFCSRGELGDFDYWGQGTTLTVSS (SEQ ID NO: 17). The light chain variable region of the murine hybridoma monoclonal antibody mAbO16: VVLMTQTPLSLPVSLGDQASISCRSSQNIVHSDGTTYLEWYLQKPGQSPKLLIYKVSNRFSGVP DRFSGSGSGTDFTLKISRVEAEDLGIYYCFQGSHVPWTFGGQTKLE NO: 18. Murine CDR sequences according to Chothia's numbering rules are shown in Table 3: nQ / onn / Lznz / e / YiAi Table 3. CDR sequences of murine anti-human CD79B antibodies CDR mAbO15 mAbO16 mAbO17 CDR1 heavy chain GSSFTSY (SEQ ID NO: 7) GYIFTNY (SEQ ID NO: 23) GYTFTTY (SEQ ID NO: 13) CDR2 heavy chain FPRSGN (SEQ ID NO: 8) FPGSGN (SEQ ID NO: 24) YPRSGN (SEQ ID NO: 14) CDR3 Heavy Chain GDLGDFDY (SEQ ID NO: 9) GELGDFDY (SEQ ID NO: 25) GSDYDGDFAY (SEQ ID NO: 15) Light Chain CDR1 RSSQSIVHSDGNTYFE (SEQ ID NO: 10) RSSQNIVHSDGTTYLE (SEQ ID NO: 26) RSSQSIVHHDGNTYLE (SEQ ID NO: 16) Light Chain CDR2 KVSNRFS (SEQ ID NO: 11) CDR3 of light chain FQGSHVPWT (SEQ ID NO: 12) nQ / onn / Lznz / e / YiAi Example 4. Humanization of human anti-CD79B antibodies After aligning the homology of the light and heavy chain sequences of the murine anti-CD79B monoclonal antibodies obtained in Example 3 with the antibody database, a humanized antibody model was established. Based on the model, optimal humanized anti-CD79B monoclonal antibodies were selected as preferred molecules by reverse mutation screening. This method began by searching the published murine Fab crystal structure model database (such as the PDB database) for crystal structures similar to or homologous with those of the obtained murine candidate molecules. High-resolution Fab crystal structures (such as <2.5 Å) were selected for establishing a mouse Fab model. The light and heavy chain sequences of the mouse antibody were then compared with the sequences in the model.Sequences consistent with the murine antibody sequences in the model were retained to obtain the murine antibody structure model; inconsistent amino acids were the potential sites of back mutation. The murine antibody structure model was run using the Swiss-pdb viewer software to optimize energy (minimization). Different amino acid positions in the model (except for the CDRs) were reverse mutated, and the resulting mutant (humanized) antibodies were compared to the pre-humanization antibodies for activity detection. Humanized antibodies with good activity were retained. Subsequently, the CDR regions were optimized, including the prevention of glycosylation, deamidation, and oxidation sites. The antibodies described above were cloned, expressed, and purified using gene cloning and recombinant expression methods. After detection by SPR, etc.Finally, the humanized antibodies hAbO15 and hAbO17, which retained the best activity, were selected. See Table 4 for specific data. The humanized antibodies hAbO15 and hAbO17 maintained similar affinity and related functions to murine monoclonal antibodies. nQ / onn / Lznz / e / YiAi Table 4. Results of identification of humanized anti-CD79B antibodies Detection Method Protein / Cell Line SN8 hAbO15 hAb017 SPR Detection (KcZ, nM) Human CD7 9B-HIS Protein 5.98 0.43 3.77 Cell Death Experiment (ICS0, ng / ml) DoHH2 Cells 4229.0 473.5 / Raji Cells >10000 >10000 / Cross-Species Reactivity Human CD7 9B-HIS Protein Yes Yes Yes Cyno CD7 9B-HIS Protein No No No Murine CD79B-His Protein No No No Thermal Stability Detection DSC (Tm, °C) 63 60 65 DLS (Labeling, °C) 61 62 67 (Note: / means that no detection was performed) The sequences of the humanized antibodies hAbO15 and hAbO17 are shown below. The heavy chain sequence of the humanized antibody hAbO15: EVQLVQSGAEVKKPGSSVKVSCKASGSSFSSYGINWVKQAPGQGLEWIGEIFPRSGNTYYNEKFEGRATL TADKSTSTAYMELRSLRSEDTAVYYCAKGDLGDFDYWGQGTTVTVSSASTKGPSVFPLAPSSKSTSGGTA ALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTK VDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVD GVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG NVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 19). The light chain sequence of the humanized antibody hAbO15: DFVMTQTPLSLPVTPGEPASISCRSSQSIVHSDGNTYFEWYLQKPGQSPKLLIYKVSNRFSGVPDRFSGS GSGTDFTLKISRVEAEDVGVYYCFQGSHVPWT FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (SEQ ID NO: 20). The heavy chain sequence of the humanized antibody hAbO17: EVQLVQSGAEVKKPGASVKVSCKASGYTFTTYGINWVKQAPGQGLEWIGEIYPRSGNIYYNEKFKGKATL TADKSTSTAYMELRSLRSDDTAVYYCARGSDYDGDFAYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGG TAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSN TKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWY VDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQ QGNVFSCSVMHEALHNHYTQKSLSLSPGK (SEQ ID NO: 21). The light chain sequence of the humanized antibody hAbO17: DVVMTQTPLSLPVTPGEPASISCRSSQSIVHHDGNTYLEWYLQKPGQSPQLLIYKVSNRFSGVPDRFSGS GSGTDFTLKISRVEAEDVGVYYCFQGSHVPWT FGGGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCL LNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (SEQ ID NO: 22). Example 5. Endocytosis of anti-CD79B antibodies To test whether the CD79B antibodies of the present invention could endocytose into cells along with human CD79B after binding to human CD79B, an endocytosis experiment was performed with DOHH-2 cells (DSMZ, ACC 47) with a high level of human CD79B protein expression to evaluate the endocytic capacity of the antibodies. DOHH-2 cells were cultured using the conventional method suitable for cells in suspension. The complete medium composition was: RPMI 1640 medium (GIBCO, Cat No.: 11835-030), plus 10% (v / v) of nQ / onn / Lznz / e / YiAi fetal bovine serum (FBS) (GIBCO, Cat No.: 10099-141) and penicillin / streptomycin (GIBCO, Cat No. 15070-063). In the experiment, cells were collected by centrifugation at 4°C, 1000 rpm for 5 min. The cells were resuspended in 10–15 ml of ice-cooled FACS buffer. The FACS buffer consisted of phosphate-buffered saline (PBS), pH 7.4, plus 2% fetal bovine serum (FBS). Throughout the experiment, the FACS buffer was pre-cooled on ice. After centrifugation and counting, the cells were added to a 96-well plate at 300,000 cells / well. After centrifugation and discarding the supernatant, 12.5 pg / ml of iron blocking solution (BD, cat. no.: 564220) was added at 100 µA / well. The cells were then blocked at room temperature for 10 min. Next, 20 pg / ml of the CD79B antibodies to be tested were added to the corresponding wells and incubated at 4°C in the dark for 1 h. The cells were washed twice with pre-cooled PBS buffer to remove unbound antibodies.Complete cell medium (RPMI 1640 medium with 10% fetal bovine serum) was added, and the cells were incubated at 37°C and 5% CO2 for 0, 1 h, 2 h, and 4 h. After centrifugation and discarding the supernatant, 100 µA / well of 2% PFA buffer was added. The cells were resuspended and allowed to stand for 10 min. The cells were then washed three times with FACS buffer, followed by 100 µA of secondary antibody solution (fluorescently labeled goat anti-human secondary antibody: 1:250 dilution with a concentration of 2 pg / ml, Biolegend, Cat # 409304) and incubated at 4°C in the dark for 0.5 h. Pre-cooled PBS buffer was added and the mixture was centrifuged at 4°C to discard the supernatant, repeating three times. The cells were resuspended in FACS buffer at 200 μA / well and detected by flow cytometry (BD FACS Calibur). The results showed that none of the three antibodies, SN8, hAbO15, and hAbO17, were endocytosed by DOHH-2 cells when incubated at 4°C. However, when incubated at 37°C, most of the antibodies were endocytosed by DOHH-2 cells after 1 h, with antibody endocytosis peaking after 4 h. All three antibodies were relatively well endocytosed.

Claims

1. A human anti-CD79B antibody or an antigen-binding fragment thereof, comprising any selected from the following (I) to (III): (I) a heavy chain variable region, comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 7, SEQ ID NO: 8 and SEQ ID NO: 9, respectively; and a light chain variable region, comprising LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; (II) a heavy chain variable region, comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 13, SEQ ID NO: 14 and SEQ ID NO: 15, respectively; and a light chain variable region, comprising LCDR1, LCDR2 and LCDR3 as shown in SEQ ID NO: 16, SEQ ID NO: 11 and SEQ ID NO: 12, respectively; (III) a heavy chain variable region, comprising HCDR1, HCDR2 and HCDR3 as shown in SEQ ID NO: 23, SEQ ID NO: 24 and SEQ ID NO: 25, respectively;and a variable light chain region, comprising LCDR1, LCDR2, and LCDR3 as shown in SEQ ID NO: 26, SEQ ID NO: 11, and SEQ ID NO: 12, respectively. nQ / onn / Lznz / e / YiAi; 2. Human anti-CD79B antibody or antigen-binding fragment thereof according to claim 1, wherein: the variable region of the heavy chain comprises: the sequence as shown in SEQ ID NO: 3 or the sequence having at least 90%, 95%, 98%, 99% identity with SEQ ID NO: 3; or the sequence as shown in SEQ ID NO: 5 or the sequence having at least 90%, 95%, 98%, 99% identity with SEQ ID NO: 5; the sequence as shown in SEQ ID NO: 17 or the sequence having at least 90%, 95%, 98%, 99% identity with SEQ ID NO: 17; and / or the variable region of the light chain comprises: the sequence as shown in SEQ ID NO: 4 or the sequence with at least 90%, 95%, 98%, 99% identity with SEQ ID NO: 4; or the sequence as shown in SEQ ID NO: 6 or the sequence with at least 90%, 95%, 98%, 99% identity with SEQ ID NO: 6; the sequence as shown in SEQ ID NO: 18 or the sequence with at least 90%, 95%, 98%, 99% identity with SEQ ID NO: 18;Preferably, the heavy chain variable region of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 3, and the light chain variable region is as shown in SEQ ID NO: 4; or preferably, the heavy chain variable region of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 5, and the light chain variable region is as shown in SEQ ID NO: 6; or preferably, the heavy chain variable region of the human anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 17, and the light chain variable region is as shown in SEQ ID NO:

18. nQ / onn / Lznz / e / YiAi; 3. Human anti-CD79B antibody or antigen-binding fragment thereof according to claim 1 or 2, which is a murine antibody, a chimeric antibody, a human antibody or a humanized antibody or fragment thereof.

4. Human anti-CD79B antibody or antigen-binding fragment thereof according to claim 3, which is a humanized antibody with its heavy chain comprising: the sequence as shown in SEQ ID NO: 19 or the sequence having at least 90%, 95%, 98% or 99% identity with SEQ ID NO: 19; or the sequence as shown in SEQ ID NO: 21 or the sequence having at least 90%, 95%, 98% or 99% identity with SEQ ID NO: 21; and / or the light chain comprising: the sequence as shown in SEQ ID NO: 20 or the sequence having at least 90%, 95%, 98% or 99% identity with SEQ ID NO: 20; or the sequence as shown in SEQ ID NO: 22 or the sequence with at least 90%, 95%, 98% or 99% identity with SEQ ID NO: 22; preferably, the heavy chain of the anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 19, and the light chain is as shown in SEQ ID NO: 20;or preferably, the heavy chain of the anti-CD79B antibody or antigen-binding fragment is as shown in SEQ ID NO: 21, and the light chain is as shown in SEQ ID NO: 22.; 5. Human anti-CD79B antibody or antigen-binding fragment thereof according to claim 3 or 4, wherein: the variable heavy chain region of the humanized antibody comprises the heavy chain frame region of human IgG1, IgG2, IgG3 or IgG4 or a variant thereof; the antigen-binding fragment is selected from the group consisting of Fab, Fab'-SH, Fv, scFv and / or (Fab')2 fragment; preferably, the variable heavy chain region of the humanized antibody comprises the heavy chain frame region of human IgG1, IgG2 or IgG4; more preferably, the variable heavy chain region of the humanized antibody comprises the heavy chain frame region of human IgG1 or IgG2.

6. An antibody-drug conjugate, wherein the antibody comprises the human anti-CD79B antibody or its antigen-binding fragment according to any one of claims 1 to 5; preferably, the antibody-drug conjugate comprises a cytotoxic agent; more preferably, the cytotoxic agent is selected from the group consisting of toxin, chemotherapeutic agent, antibiotic, radioisotope, and nucleolytic enzyme. nQ / onn / Lznz / e / YiAi 7. A polynucleotide encoding the human anti-CD79B antibody or its antigen-binding fragment according to any of claims 1 to 5.

8. A vector comprising the polynucleotide according to claim 7, which is a eukaryotic expression vector, a prokaryotic expression vector, or a viral vector.

9. A host cell comprising the vector according to claim 8, preferably the host cell being a bacterium, yeast or mammalian cell; more preferably the host cell being an Escherichia coli, Pichia pastoris, a Chinese hamster ovary cell or human embryonic kidney cells.

10. A method for preparing the human anti-CD79B antibody or its antigen-binding fragment, comprising: expressing the human anti-CD79B antibody or its antigen-binding fragment in the host cell according to claim 9, and isolating the human anti-CD79B antibody or its antigen-binding fragment from the culture.

11. A pharmaceutical composition comprising: any one or any combination thereof selected from the following: the anti-CD79B antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, the antibody-drug conjugate according to claim 6, the polynucleotide according to claim 7, the vector according to claim 8; and, optionally, a pharmaceutically acceptable excipient, diluent or vehicle.

12. Use of any selected from the following in the preparation of a drug or pharmaceutical composition: the human anti-CD79B antibody or its antigen-binding fragment according to any one of claims 1 to 5, the antibody-drug conjugate according to claim 6, the polynucleotide according to claim 7, the vector according to claim 8, wherein: the drug or pharmaceutical composition is used to treat a proliferative disease or to delay the progression of a proliferative disease, preferably, the proliferative disease is cancer or a tumor; more preferably, the cancer or tumor is lymphoma or leukemia; the lymphoma is selected from the group consisting of diffuse large B-cell lymphoma, non-Hodgkin lymphoma, small lymphocytic lymphoma, and mantle cell lymphoma; the non-Hodgkin lymphoma is selected from the group consisting of aggressive NHL, relapsed aggressive NHL, relapsed painless NHL, refractory NHL, refractory painless NHL;Leukemia is selected from the group consisting of chronic lymphocytic leukemia, hairy cell leukemia, and acute lymphocytic leukemia. nQ / onn / Lznz / e / YiAi; 13. A method for treating or preventing a proliferative disease or delaying the progression of a proliferative disease, the method comprising: administering to a subject a therapeutically effective or disease-delaying effective amount of the human anti-CD79B antibody or antigen-binding fragment thereof according to any one of claims 1 to 5, the antibody-drug conjugate according to claim 6, the polynucleotide according to claim 7, the vector according to claim 8, the pharmaceutical composition according to claim 11, or any combination thereof, preferably, the proliferative disease being cancer or tumor; more preferably, the cancer or tumor being lymphoma or leukemia; the lymphoma being selected from the group consisting of diffuse large B-cell lymphoma, non-Hodgkin lymphoma, small lymphocytic lymphoma, and mantle cell lymphoma;Non-Hodgkin lymphoma is selected from the group consisting of aggressive NHL, recurrent aggressive NHL, recurrent painless NHL, refractory NHL, and refractory painless NHL; leukemia is selected from the group consisting of chronic lymphocytic leukemia, hairy cell leukemia, and acute lymphocytic leukemia.