Anti-CD123 antibodies and conjugates and derivatives thereof

Abstract

2022291603 23 Dec

Description

ANTI-CD123 ANTIBODIES AND CONJUGATES AND DERIVATIVES THEREOF REFERENCE TO RELATED APPLICATIONS This application is a divisional of Australian Patent Application No. 2016285552, the entire content of which is incorporated herein by reference. FIELD OF THE INVENTION The present invention generally relates to antibodies, antigen-binding fragments thereof, polypeptides, and immunoconjugates that bind to CD123 antigen (the « chain of the interleukin-3 receptor, or IL-3Ra). The present invention also relates to methods of using such CD123-binding molecules for diagnosing and treating diseases, such as B-cell malignancies. BACKGROUND OF THE INVENTION CD123 (interleukin 3 receptor alpha, IL-3Ra) is a 40 kDa molecule that is part of the interleukin 3 receptor (IL-3R) complex. The cytokine Interleukin 3 (IL-3) drives early differentiation of multipotent stem cells into cells of the erythroid, myeloid and lymphoid progenitors. CD123 is expressed on CD34"-committed progenitors, but not by CD347 / CD38" normal hematopoietic stem cells (HSCs). CD123 is expressed by basophils, mast cells, plasmacytoid dendritic cells, some expression by monocytes, macrophages and eosinophils, and low or no expression by neutrophils and megakaryocytes. Some non-hematopoietic tissues, such as placenta, Leydig cells of the testis, certain brain cell elements and some endothelial cells, also express CD123. However, expression there is mostly cytoplasmic. CD123 is reported to be expressed by leukemic blast cells (“leukemia blasts”) and leukemia stem cells (LSC) (Jordan er al., Leukemia 14:1777-1784, 2000; Jin et al., Blood 113:6603-6610, 2009). In human normal precursor populations, CD123 is expressed by a subset of hematopoietic progenitor cells (HPC), but not by normal HSCs. CD123 is also reportedly expressed by plasmacytoid dendritic cells (pDC) and basophils, and, to a lesser extent, monocytes and eosinophils. CD123 has been reported to be overexpressed on malignant cells in a wide range of hematologic malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (Muiioz et al., Haematologica 86(12):1261-1269, 2001). Overexpression of CD123 is associated with poorer prognosis in AML (Tettamanti et al., Br. J. Haematol. 161:389-401, 2013). AML and MDS are thought to arise in and be perpetuated by a small population of leukemic stem cells (LSCs), which are generally dormant (i.e., not rapidly dividing cells) and therefore resist cell death (apoptosis) and conventional chemotherapeutic agents. LSCs are characterized by over-expression of CD123, while CD123 is not present in the corresponding normal hematopoietic stem cell population in normal human bone marrow (Jin et al., Blood 113:6603-6610, 2009; Jordan et al., Leukemia 14:1777-1784, 2000). CD123 expression is also associated with multiple other malignancies / pre-malignancies: chronic myeloid leukemia (CML) progenitor cells (including blast crisis CML); Hodgkin's Reed Sternberg (RS) cells; transformed non-Hodgkin's lymphoma (NHL); some chronic lymphocytic leukemia (CLL) (CD11c"); a subset of acute T lymphoblastic leukemia (T-ALL) (16%, most immature, mostly adult), plasmacytoid dendritic cell (pDC) (DC2) malignancies and CD34 / CD38" myelodysplastic syndrome (MDS) marrow cell malignancies. AML is a clonal disease characterized by the proliferation and accumulation of transformed myeloid progenitor cells in the bone marrow, which ultimately leads to hematopoietic failure. The incidence of AML increases with age, and older patients typically have worse treatment outcomes than do younger patients (Robak et al., Clin. Ther. 2:2349- 2370, 2009). Unfortunately, at present, most adults with AML die from their disease. Treatment for AML initially focuses in the induction of remission (induction therapy). Once remission is achieved, treatment shifts to focus on securing such remission (post- remission or consolidation therapy) and, in some instances, maintenance therapy. The standard remission induction paradigm for AML is chemotherapy with an anthracycline / cytarabine combination, followed by either consolidation chemotherapy, usually with higher doses of the same drugs as were used during the induction period, or human stem cell transplantation, depending on the patient's ability to tolerate intensive treatment and the likelihood of cure with chemotherapy alone (see Roboz, Curr. Opin. Oncol. 24:711-719, 2012). Agents frequently used in induction therapy include cytarabine and the anthracyclines. Cytarabine, also known as AraC, kills cancer cells and other rapidly dividing normal cells by interfering with DNA synthesis. Side effects associated with AraC treatment include decreased resistance to infection, a result of decreased white blood cell production; bleeding, as a result of decreased platelet production; and anemia, due to a potential reduction in red blood cells. Other side effects include nausea and vomiting. Anthracyclines (e.g., daunorubicin, doxorubicin, and idarubicin) have several modes of action including inhibition of DNA and RNA synthesis, disruption of higher order structures of DNA, and production of cell damaging free oxygen radicals. The most consequential adverse effect of anthracyclines is cardiotoxicity, which considerably limits administered life-time dose and to some extent their usefulness. Thus, unfortunately, despite substantial progress in the treatment of newly diagnosed AML, 20% to 40% of patients do not achieve remission with the standard induction chemotherapy, and 50% to 70% of patients entering a first complete remission are expected to relapse within 3 years. The optimum strategy at the time of relapse, or for patients with the resistant disease, remains uncertain. Stem cell transplantation has been established as the most effective form of antileukemic therapy in patients with AML in first or subsequent remission (Roboz, 2012). Antibody-drug conjugates (ADC) and other cell binding agent-drug conjugates are emerging as a powerful class of anti-tumor agents with efficacy across a range of cancers. Cell binding agent-drug conjugates (such as ADCs) are commonly composed of three distinct elements: a cell-binding agent (e.g., an antibody); a linker; and a cytotoxic moiety. Conventionally, the cytotoxic drug moiety is covalently attached to lysine residues on the antibody, or to cysteine residues, obtained through reduction of interchain disulfide bonds, resulting in ADCs that are heterogeneous mixtures bearing varying numbers of drugs attached at different positions on the antibody molecule. SUMMARY OF THE INVENTION The present invention is based on the surprising findings that the conjugates of the present invention are highly potent against various CD123-expressing cancer cells, particularly leukemia with at least one negative prognostic factors. One aspect of the invention provides an antibody or antigen-binding fragment thereof that: (a) binds an epitope within amino acids 101 to 346 of human CD123 / IL3-Ra antigen, and (b) inhibits IL3-dependent proliferation in antigen-positive TF-1 cells. In certain embodiments, the antibody or antigen-binding fragment thereof binds an epitope within amino acids 101 to 204 of human CD123 antigen. In another embodiment, the antibody or antigen-binding fragment thereof binds an epitope within amino acids 205 to 346 of human CD123 antigen. A related aspect of the invention provides an antibody or antigen-binding fragment thereof that: (a) binds an epitope within amino acids 1 to 100 of human CD123 antigen, and (b) inhibits IL3-dependent proliferation in antigen-positive TF-1 cells, with an ICsp value of 0.1 nM or less (e.g., 0.08 nM, 0.05 nM, 0.03 nM). In certain embodiments, the antibody or antigen-binding fragment thereof inhibits the proliferation of leukemic stem cells or leukemic blast cells but not hematopoietic stem cells. In certain embodiments, the antibody or antigen-binding fragment thereof binds to human CD123 antigen-positive cells with a dissociation constant (Ka) of 0.3 nM or lower, such as between 0.01 nM and 0.3 nM, between 0.01 nM and 0.2 nM, between 0.01 nM and 0.19 nM, between 0.01 nM and 0.18 nM, between 0.01 nM and 0.15 nM, or between 0.01 nM and 0.1 nM. In certain embodiments, the antibody or antigen-binding fragment thereof binds to cynomolgus monkey CD123. For example, the antibody or antigen-binding fragment thereof may bind to cynomolgus monkey CD123 with a Kq of between 0.05 and 0.3 nM, between 0.05 and 0.2 nM, between 0.05 nM and 0.19 nM, between 0.05 nM and 0.18 nM, between 0.05 nM and 0.15 nM, or between 0.05 and 0.1 nM. In certain embodiments, the antibody or antigen-binding fragment thereof binds both human and cynomolgus monkey CD123 with a substantially similar binding affinity. For example, the antibody or antigen-binding fragment thereof may bind to human and cynomolgus monkey CD123 with a Kg of between 0.05 and 0.3 nM, between 0.05 and 0.2 nM, or between 0.05 and 0.1 nM. The Kq may be measured by flow cytometry, surface plasmon resonance, or radioimmunoassay. In certain embodiments, the antibody or antigen-binding fragment thereof inhibits at least 50% of IL3-dependent proliferation in antigen-positive TF-1 cells at a concentration of 0.5 nM or lower. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) at least one heavy chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR is selected from the group consisting of: SEQ ID NOs: 1, 5, and 12, CDR2 is selected from the group consisting of: SEQ ID NOs: 2, 3, 6-10, 13, and 14, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 4, 11, 15 and 70; and b) at least one light chain variable region or fragment thereof comprising three sequential complementarity- determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDRI is selected from the group consisting of: SEQ ID NOs: 16, 19, 20, 23 and 72, CDR2 is selected from the group consisting of: SEQ ID NOs: 17, 21, 24 and 71, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 18, 22, and 25. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) at least one heavy chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR is selected from the group consisting of: SEQ ID NOs: 1, 5, and 12, CDR2 is selected from the group consisting of: SEQ ID NOs: 2, 3, 6-10, 13, and 14, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 4, 11 and 15; and b) at least one light chain variable region or fragment thereof comprising three sequential complementarity- determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR1 is selected from the group consisting of: SEQ ID NOs: 16, 19, 20 and 23, CDR2 is selected from the group consisting of: SEQ ID NOs: 17, 21, and 24, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 18, 22, and 25. In certain embodiments, the conservative amino acid substitutions comprise a substitution of at least one Lys in a CDR by an Arg. In certain embodiments, the antibody is a CDR-grafted humanized antibody comprising mouse CDR regions, and wherein one or more (e.g., 1, 2, 3,4, 5, 6, 7, or 8) heavy chain and / or light chain framework region vernier zone residues of said antibody is of mouse origin. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 34; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa, the second residue from the N-terminus of SEQ ID NO: 34, is Phe. In other embodiments, Xaa is Val. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40, except that the N-terminal residue is Ser; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41, except that the N-terminal residue is Ser. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the N-terminal residue is Ser, and except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys (i.e., Cys at EU / OU numbering position 442); and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41, except that the N-terminal residue is Ser. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 38; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 34; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 56; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, Xaa, the second residue from the N-terminus of SEQ ID NOS: 38, 34, 56, and 54, is Phe. In other embodiments, Xaa is Val. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa, the second residue from the N-terminus of SEQ ID NO: 54 or 56, is Phe. In other embodiments, Xaa is Val. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 1, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 2 or 3, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 4; and b) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 16, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 17, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 18. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 5, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 6, 7, 8, 9, or 10, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 11; and, b) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 19 or 20, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 21, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 22. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) an immunoglobulin heavy chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 12, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 13 or 14, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 15; and b) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 23, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 24, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 25. In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) a Vu sequence at least 95% identical to a reference Vu sequence selected from the group consisting of: SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably 26, 28, 30, 32, 34, and 38); and / or, b) a V1. sequence at least 95% identical to a reference VL sequence selected from the group consisting of: SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (preferably 27, 29, 31, 35, and 37). In certain embodiments, the Vu sequence is at least 99% identical to one of SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably 26, 28, 30, 32, 34, and 38), and / or wherein the V1 sequence is at least 99% identical to one of SEQ ID NOs: 27,29, 31, 33, 35, 37, and 41 (preferably 27, 29, 31, 35, and 37). In certain embodiments, the antibody or antigen-binding fragment thereof may comprise: a) a Vu sequence selected from the group consisting of SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably 26, 28, 30, 32, 34, and 38); and / or, b) a Vi sequence selected from the group consisting of SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (preferably 27, 29, 31, 35, and 37). In certain embodiments, the antibody or antigen-binding fragment thereof may comprise a Vu sequence of SEQ ID NO: 26 and a V1 sequence of SEQ ID NO: 27, or a Vu sequence of SEQ ID NO: 28 and a V1 sequence of SEQ ID NO: 29, or a Vu sequence of SEQ ID NO: 30 and a Vi. sequence of SEQ ID NO: 31, or a Vu sequence of SEQ ID NO: 34 and a V1. sequence of SEQ ID NO: 35. In certain embodiments, the antibody is a murine, non-human mammal, chimeric, humanized, or human antibody. For example, the humanized antibody may be a CDR- grafted antibody or resurfaced antibody. In certain embodiments, the antibody is a full-length antibody. In certain embodiments, the antigen-binding fragment thereof is an Fab, Fab’, F(ab’),, Fy, single chain Fv or scFv, disulfide linked Fy, V-NAR domain, IgNar, intrabody, IgGACH2, minibody, F(ab’), tetrabody, triabody, diabody, single-domain antibody, DVD-Ig, Fcab, mAb;, (scFv), or scFv-Fc. Another aspect of the invention provides a polypeptide comprising the Vi and Vi sequences of any of the subject antibody or antigen-binding fragment thereof. The polypeptide may be a fusion with a protein that is not a pseudomonas toxin. Another aspect of the invention provides a cell producing the antibody or antigen- binding fragment thereof of the invention, or the polypeptide of the invention. Another aspect of the invention provides a method of producing the antibody or antigen-binding fragment thereof of the invention, or the polypeptide of the invention, comprising: (a) culturing the cell of the invention; and, (b) isolating the antibody, antigen- binding fragment thereof, or polypeptide from the cultured cell. In certain embodiments, the cell is eukaryotic cell. Another aspect of the invention provides an immunoconjugate having the following formula: ceat-cy), wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, that is covalently linked through a lysine residue to Cyl; Woy is an integer from 1 to 20; and Cyl! is represented by the following formula:, Lm YX N, 0. o. HN—¢ 0 L Zn, YX Xx ~~ Nel Yod, on CN os o 0 RG Ne] wh e—4 6 YF =N, 0. 0. HN—, Cool, 0 0 @ 0 = 0 o ~ or RS Tl we— 8 0 YX X. y 7 N_ / =N o. o Net, o or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1- Cay)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SO:M; W’ is -NR¢, R® is -(CH,-CH-0)s-R¥; nis an integer from 2 to 6; Rk is -H or -Me; R® is a (C)-Ce)alkyl; L’ is represented by the following formula: -NR;s-P-C(=0)-(CRaRb)m-C(=0)- (BI); or -NR;s-P-C(=0)-(CR:Rb)m-S-Z°!- (B37); Rs is -H or a (C1-Ca)alkyl; P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues; Ra and Ry, for each occurrence, are each independently -H, (Ci- Cs)alkyl, or a charged substituent or an ionizable group Q; m is an integer from 1 to 6; and Z*! is selected from any one of the following formulas: a A 3 yo 0 o A crag Ls ~ Dy Ag oO (hy) 0 (bl); Oo (b2); 0 (b3); SoM 5, A ath AAA (bd): (b4); o (b5), Q g q Sep herhe 0 [ (b6), Ty 0 No 0 ~ A A To (b7); o (b8); oO (b9); and 2 0 A b a SOM SOM Fn AAA (b10), wherein: q is an integer from 1 to 5; and Mis H® or a cation. In certain embodiments, R, and Ry, are both H; and Rs is H or Me. In certain embodiments, P is a peptide containing 2 to 5 amino acid residues. For example, P may be selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N’- nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala- Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe- Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In certain embodiments, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In certain embodiments, Q is -SOsM. In certain embodiments, the immunoconjugate is represented by the following formula: Tt JHE HN bl Pes oo Dao | a IA, : i Jw o H o H o | AA pees fn mnt < ee poe > | N ‘OMe MeO’ 3 o o Jw Arete X a <r Ke Wg l Tole WIA p- xX FE. x 2 Sow ~~ I a Yo reo GH Lh ’ 5 8 Ju dwn ~~ NS 2 4wY? H I vo Hy 0 nA a Neg > Looe Li 5 & Fo Ks ° MN AN Ae <A OL. Wooo | GH ENON > bo J 2 on XR ican AAS I ° N, o. o. Neg > Con WC | o 0 Hw o o H |g tthcan N TH 0° u y N 0. 0. Nf > N OMe MeO’ | J Zw 0 0° H IE Kidosa N HN NNSA TH ° Zz x Yoo Ly A a Nef > Cm MeO N © Aw Loti SAK font N YN NjCBA o x Oo < 8 NesY 0. 0, =f N: ‘OMe MeO N, o o 3 Su, sot SAE, - x z 2 Lr © Fee NF » a a o SOM i. : Non CBA NISSEN ANA Lo Tx o < 8 o o Nf > » C “on or 20 b d | ) > = A Oo Oo OM Ho, My wisi AS Xx : 0 Yl X ° dno Don N OMe MeO’ N, | o 0 Sh | = Hop, 1 Ro 1 ican 2 s. retry H PY > N 0. 0. Nef ( Com nee | b d 5" ow BN A con |W De Cor | yo | Sad ~~ J wi. JH 3 Refcan HNN Be, CY RNY < falo o nf > (on SoG J J. | x Sa 0 Ho 0 it : Non CBA WY THK AA cl x Xx o MN NeW Ned > Com XS | 5 d ) Jw ou 0 SOM f- N= s New CBA Woy ply NAY bs $C pce De Jd > (e * on or GC (A b J | 7 xX Q a > | ~~ x L Jw a fo) SOM fe NA s Netw CBA AAA AA x : TH s 0 ] Xo > YSN o. o. Nef ® o oe wt CL b J of Ju, eA A oi 8 Sioa < ; . ALT 7 Ng 0 5 Gr AA J: | > ~ Jw, 2H ~ An oo i HN N SS PO fos BLISS TT =N, 0. 0. Nef > N OMe TS 5 J Jw > ns Aw bi 3 Rebmcon HN ‘ N A N’ S\ < f o o Nef > (Con 4 o o yo | fd Hu, 2H 2 fice HN SNS SY SS " AN 0. 0. Ref > om oe 0 ° Ju <8 Cl. > LF = J IR 1 ficen NA s. Y N, < fl 0. 0. hey > ( Cnn nee | 0 o ofa Jw 0. ° ) | Lon oth, oT go | NF x \ Jy, 9 o SoM H +H NA S. Nev CBA AAI A 4. H =e Xv ° 4 A a Lad > N OMe Se d J. | x Sw o 0 SOM a ON AS pen : H § v ¥ °C oxy 2 -N o 0. Nef > Com XS | b J ) Jw 0 4 ~~" 0 SOM fid-con NA s. adh dn se ASE A TH © 0 ZN x \ ~~ A ~ < 8 C1. Ly > i a! A A < Rao oN! ( Con A b d H NX x ry." > > ~ Jw 2 AE Ena ANT mK vw X © xy 2 N o o. Ne / ” Doe OMe A 0 0 L ffir Aw, < No 1 oo oy h > doh 5 i ne < LK ALT 2 Is is ow 2 uy Y { Ee FoI ’ | { le MeO’ 7 3 Jw < HN CO 1 Fa x > 25 Jones PON HN N’ el < f ool 7 : > GH AA J +» no fh oO Toy xy ° de om el a ae fad > il ka { Jw IH Yo i NJ s. Netw CBA Y wy YK ~~ LO roy > = 0. 0. Nef om oe o 0 Ju Jw <8 Cl. > S WY9 SOM i No A s. Nef CBA Woy YK NAY X $< Aa = r Pe a | o o ) Jw H xX rr OC oor 0 CYL tx ° iN. ae Br cae a ow N= ou ~ o SOM in Hg s Non CBA WY YX Na vf Ce Tay © =N, 0. 0. Ne / . > Con wl | ° 0° ) ow H 0. 0. Nommrmsnnooefoon GBA ANOS Xx o NA N 0. 0. > N OMe MeO N, | o o Woo sor X | i CBA Sinusitis po Nel wy = OMe MeO’ Y Ly) ct . or a pharmaceutically acceptable salt thereof, wherein Wr is an integer from 1 to 10; the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when itis a single bond, X is -H, and Y is -OH or -SOsM. A related aspect provides an immunoconjugate having the formula: CBA +o), wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, that is covalently linked to Cy? through a lysine residue; W. is an integer from 1 to 20; and Cy"? is represented by the following formula: RL Srp N YF N 0. 0. HN—¢ Cocoon, 3 I . Xx 7 os ~ RR 24 x 7 1 Nr Some MeO’ N I) J . ws zy yy, X -N, ° ° HN—, N. 0 o . = 9 oO Tor RZ we s-z5-} Y. X X, =H, 2. nr LOTT Cn 0 o . or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (Ci- Cas)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SO:M; R*! and R® are independently (C;-Ce)alkyl; R¢ is -H or a (C;-Cs)alkyl; W’ is -NR¢, R* is -(CH-CH;-0):-R¥; n is an integer from 2 to 6; Ris -H or -Me; Z%! is selected from any one of the following formulas: mcr Ae . 0 bl); rr (bl); o (b2); 0 (b3); o gong 3 OM As An YY (bd): ~Y 5), Ford hrp he 0 [ (b6), 0 (Saas £ ML Ts Tn > (b7); o (b8); o ° (b9); and “J 7 0 A 0 ( SOM AAA 0 ¢ (b10), wherein: q is an integer from 1 to 5; and Mis -H™ or a cation. In certain embodiments, R® is H or Me; R*! and R*? are independently -(CHa)p- (CR'RY)-, wherein Rf and R# are each independently -H or a (C1-Ca)alkyl; and pis 0, 1, 2 or 3: In certain embodiments, Rf and RE are the same or different, and are selected from -H and -Me. In certain embodiments, the immunoconjugate is represented by the following formula: - gS on R OL Lo > J. X ). args fess % A Oa Lo > bs ee “TQ tooo Or SH 20h, | > { at ™ TO J LN Oa J Rt ° FS Gh, : NS { cys ™ “TO J I oh L ae TIO J. BN A Ce WJ ° > > L as “TIO J. wisn te ion Cah > J. > wg YJ Ly A Loo Ae > | So AA J J. Angry Ssgr yf fcon X 0 th nonin ZX ‘OMe A & w H LONGO Sig itcsa ¥ 2 XS MeN o. NY > om wl ° ° w SoM |, ws Xx o has oni Fb en CL Q woo. sor SOM fhecsn S., ON ~T . AY J ) AN) MeO : a em ] (J ® FZ or a pharmaceutically acceptable salt thereof, wherein Wr is an integer from 1 to 10; the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when itis a single bond, X is -H and Y is -OH or -SO3M. In certain embodiments, the double line == between N and C represents a double bond, X is absent and Y is -H. In certain embodiments, the double line == between N and C represents a single bond, X is -H, and Y is -SOsM. In certain embodiments, M is H*, Na* or KK. Another related aspect of the invention provides an immunoconjugate having the formula: CBA Hor), wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide of the invention, which is covalently linked to Cy" through a Lys residue; ‘Wi is an integer from 1 to 20; CyL3 is represented by the following formula: 0 a m iy 9 vx ° R® MeO OY SEAN 1 Med’ nd N © Co m’is1or2; Ri and Ry, are each independently H or a (Ci-Cs)alkyl; and 27! is selected from any one of the following formulas: ~~ Ae . 0 (bl); o (b2); 0 (b3); oO Arend, = SoM AAP n AAP n oer (b6), o ~ 0 ~ AN A 10a Fem OB 8): and © © boy, ? 0 TA o} It wherein: q is an integer from 1 to 5; and M is H™ or a cation. In certain embodiments, m’ is 1, and R; and R are both H. In certain other embodiments, m’ is 2, and R; and R» are both Me. In certain embodiments, the immunoconjugate is represented by the following formula: Q No S: § NeenCBA oo o SOM 1A 1 9 eo, N . a 0 = PY) wo Med HO J WL of Wy Lor Ly LR ved HO N © Zw Lor 3 BA pn HR on N N ptr rp nh o a2 RX ° < veo, N © > Ny Lo Med HO H Za . COWL Q \ S / N H Q NN S00 CBA 2X © ° cl J Fe) ° 3 MeN > 0 = ed yo / , we »vrracantieal acrantahila cali therenft whearsin Wr te ah intaaar 4 or a pharmaceutically acceptable salt thereof, wherein Wi is an integer from 1 to 10. In certain embodiments, M is H", Na“ or K*. Another aspect of the invention provides an immunoconjugate having the following formula: 1 '—Cy® ) ceadr Jeg ” wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to the Jes’ group; Wsis 1,2, 3, ord; Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety (wherein the 2-hydroxyethylamine moiety can be part of a serine, threonine, hydroxylysine, 4-hydroxyomithie or 2,4-diamino-5-hydroxy valeric acid residue) on an N-terminal of said antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, and an aldehyde reactive group on Cy*!, and is represented by the following formula: Hy H H H O Ce Ha H HEN 2 0 ERE va 2 s1 ic N Ne 82, EN st} ¢ Ho H s13-C AE . H ; sie sls H Ne=N Ne-Neg_i C=N~0— ©) ei 2. Hp {eo wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy*!; Cy*! is represented by the following formula: Foy Poy ORR Zar (CR o YX =N, o. o HN—, 0 0 Fog Pp ORR Zar (CRBS —] o x v YX Sid =, fo} 0. LL SLO MeO TY oO fo} xX RS woe — 0 YF =N, 0. 0. N=, 0 + Or RQ ww e—L 0 YX Xx y 7 A -N ° ° N=, o o . or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SOsM, and M is H* or a cation; Rs is -H or a (C;-Cs)alkyl; P is an amino acid residue or a peptide containing 2 to 20 amino acid residues; Zs is absent, -C(=0)-NRy-, or -NRy-C(=0)-; Ry is -H or a (C;-Cs)alkyl; Ra and Re, for each occurrence, are independently -H, (Ci-Cs)alkyl, or a charged substituent or an ionizable group Q; rand r’ are independently an integer from 1 to 6; W’ is -NR¢, R* is -(CH-CH;-0):-R¥; n is an integer from 2 to 6; Rk is -H or -Me; R* is a (C1-Ce)alkyl; L is -NRg-(CRaRbp): or absent; and 1 is an integer from 0 to 6. For simplicity, in each instance below reciting Ser as the N-terminal residue, it should be understood that other 2-hydroxyethylamine moiety, as part of a serine, threonine, hydroxylysine, 4-hydroxyornithie or 2,4-diamino-5-hydroxy valeric acid residue, is contemplated where applicable, especially with respect to Thr. In certain embodiments, Ra, and Ry, are both H, and Rs and Ry are both H or Me. In certain embodiments, P is a peptide containing 2 to 5 amino acid residues. For example, P may be selected from the group consisting of: Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala- Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D- Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In certain embodiments, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala- Ala, or D-Ala-D-Ala. In certain embodiments, Q is -SOsM. In certain embodiments, the immunoconjugate is represented by the following formula: n bh o , 2 H H H N N N. =, Ny ory blll = ” pyr % fd ge Ney” > SoH I | o ag » J 7 we x AN / ) xX > o 2 H H AM An AGA Nod N=C anne CBA ol Tu 0 04 H x X 1 v Y Yen Lo) Nef > Cm wn | © a < Tir os 0-4 0 H Ho: i i N. —— NSN CBA oN Tu I ~ a X i DL hf’ > IX OMe A | 0 ° J y X x 2 [ae NA tu, H 2 H 8 : 5 ~~ ao ~N N Fle x x en gel he’ 1s Son neg 0 ° \_ J > (7 ~N Js Fan Spe fi he’ > G8 20%, |g : xX X | > Ld ~ I ag re x p= a As > : 9! ‘OMe 0 © aq » ali ws A 9 H H = XH 0. af NA fe X N LL. Ny’ > 9! OMe wl 0° o Ao J 8 NS Je 2 wd RO N N— I 2 ry y fo ¥ A Xo IS i RO N NN— I SASSY tigfosa o o 2 ¥ Xx wf ond” > Cn edo 0 ° J Z NN mo A - : RT | \ G CBA GETTER an ae NN Je o © H Ho N. N “N= . Ny TY N: rp x on Ll. Newg¥ > Cm ee © J ae NS Je pry rf Cpe eke : J vs 2 H BL Ay N —CmrCBA o " o HA A x x X Yo uf B o % i > ° © J A ~ J ve i { Brgy ~~ “gen oad Cm XA SH iis } | TOs Je 8 f AoE il.” 3 Poin do a od > Cm ne l 0 o I | Tr Se omortmyAy CBA o i a Gf wpa) o l oo oo Ton Je, i i ANNONA — gfe X X "at 2 nef ” CTI o o Fw Hi H ANNONA Pega o x tooo b AL noe 1 0 o 2 ur > = Cs Ju { on EY id est do oad’ le l o o Jw \~F - Tr Av H _o. ATS, NO i danneCBA ~~ YT 1g] tooo lose 3 (X ‘OMe nee o Oo 1S <2 |G ER V4 J Ws. 0. 0. foo AO jo “YY Ng cea YON, 0. 0. Nes” i Ge AAP ° o J a. ~~ TN Hi R AON ONIN =n fo CBA ox $ Poap lind (Cm Meo N | 0 0 Ws xX ONO SNH mecBA o X x Y\ J J Y =N. a Nes / > ” - con wt C or o 0 wg H Ogg Pie CBA Ar J pa Ty fl Nef o o L > N. OMe MeO" N, o ° ws. sor X 1 H PONG Nef xr ° x YSN, 0. 0. Ney > SH m—— j o ws or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or - SOM. Another aspect of the invention provides an immunoconjugate having the following formula: 82 ceadr Jog —Cy ),. wherein: CBA is the antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to the Jcs’ group, Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of the invention, or the polypeptide thereof of the invention, 2 HM | HEN 2 s14—C BE! 2, and an aldehyde reactive group on Cy*2, and is represented by the following formula: o Hp 4 © Ha H s18—C=N< s1§—C —N~ ST3—C=N<, s1§—C —N., Hg N Ve, t Ve, Fg N jez, f N52. si H Heo Keto wo H 2, oi H, wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy®%; Cy is represented by the following formula: [o} -S. Re SR Su N HN—, A o 0 “ Np Some MeO’ N 0 o . Q, -S RR N Yo x X.Y { — =, OL. N= oO 0 . RZ wo s-Li—} % Xx -N, o. B HN—, N. oO oO . sor RZ ww” s-Li—} YX Xx } NY =N LL ot N o 0 . or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1- Cas)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SO3M; Mis H" or a cation; R*! is a (C1-Co)alkyl; Reis -H or a (C1-Cs)alkyl; W’ is -NR€, R® is -(CH,-CH-0)s-R¥; nis an integer from 2 to 6; Ris -H or -Me; R*? is a (C1-Ce)alkyl; L, is represented by the following formula: Bilis at it saat en, se a Ras Ry, s3 Za fa as qt 1 Ref Raz Q wherein: s3 is the site covalently linked to the group Jes’; s4 is the site covalently linked to the -S- group on Cy*2; Za» is absent, -C(=0)-NRg-, or -NRy-C(=0)-; Ry is -H or a (C;-Cs)alkyl; Q is H, a charged substituent or an ionizable group; Ral, Raz, Raz, Rag, for each occurrence, are independently H or (C1-Ca)alkyl; and ql and rl are each independently an integer from 0 to 10, provided that q1 and rl are not both 0. In certain embodiments, -L;- is represented by the following formula: $3 . DN CoM ss Ans ot wd u A Ns] a. gy R wR Ane # FAA AA st 0 a nn 0 sor 0 or a pharmaceutically acceptable salt thereof, wherein R is H or -SO:M. In certain embodiments, R¢ is H or Me; and R*! is -(CHz)p-(CR'R®)-, and R*? is - (CH2)p-(CR'RE)-, wherein Rf and RE are each independently -H or a (C1-Cs)alkyl; and p is 0, 1, 2 or 3. In certain embodiments, Rf and R are the same or different, and are selected from -H and -Me. In certain embodiments, the immunoconjugate is represented by the following formula: o 0 Hi N=C YIN Ny - X £ Ls Nf r o ws ss VM ¥ MF Ws. 0 0 vf a ~~ =Cicaa YX X -~ Loe N= > WC 0 0 ws. % A Y Y ~7 Ws. 3 9 H N-CAnCBA WYN Ay | x H 3 N Cs N=, 0 o J we. NE © 2 2 Megohosa YN NY [4 YF Cox =N 0, 0. Nef a re 0 o J ws. NS o Tn A: I oc Wo o hb ED AA —H ) : Y N=C CB 0. Af i SocSocky, 1 OMe MeO D 0 “ H s NS ts ade Ne NC ech x x Y, Y 4 Ja Nef 0 0 _ x # LL AF Ws s. Not HN 2 ~Y N—C [CBA H ’ xy ' WM ; Ln ° ° we a» oo Ws ; fem HN SY syEhcen y, Tox © -N. N=, > {Ce WC ° o Sir > oo Ws SOM No — HN SY can % ° x { en n=’ r io wT o 0 , LS ¥ LA. 7 ws foM y adr NAY emt fecnn C: ° YX Xa =N. 0. 0. N= > o o 2 oO - B Ws. 0 gop NSN NY SN—cmpmecaa % H Hy ° H X x x o o. Nf > ° ° | Wg o o oO LW X v =N. OAL: Nf {TC o o . Lx Sy KN ws I ‘OMe lS SE Soll Be BM rT J ws 2 8 { s. N= de CBA yr ~~ yw wr x v R ly -N 0. o. N= > {WC LOY I 5 er MW ME J ws ; 9 ret SN SN CBA HN 5 TY fal Ng H Xx —N 0. 0 > L ° 8 } NOAA OA r 4 oc J H H Ws Q OsMH H we Ay eden ” x ” )-4 i 0, N=, > oe] L ° . 7 we b 9 SOsMY 8 MOYEN NAN NYY Agee 5 4 HB % Xx x Y -N 0 0. Nef > {OG Tem ) RM > ? we Fyariatice R — =N. 0. Z 0. N=, SAT, LR 0. N==£ Sr Cs ’ } | N AAO AN ST (OF I a SE N N: I OMe MeO’ I 0) oo NS © ° 7 Jw 0 i < f 0 o. i” > N OMe MeO $5 . 0 0 | N. OAL Nef > SETI Xx 7 > s fi ~y— worse Ne NY NAP y = v K Xx ° N 0 o. Nef > { Xm lo o o Ir... 5 Nt 8 ° J ows SOM, yy An vemghrom Cox o 5 OMe MeO 9) 0 Oo T NS © °c 7 J ows 0 §osMy MENS o=g CBA YJ Ctx c -N. o. Nf > N OMe wl o 0 | 5 if 0 0 NJ © °c 7 Jw o SOsMy S. N. ~ ~e RS EA HH Y Spel . > 5: OMe lo o 0 5 ws + SOM N. ~, wy NA ges * ° TY LO o o wy N ell con EN NN rx SoM © i Cos Nt > N. SRT o oo Jus wpe A AA Fon { en a r STL 0 ws > 0 i H ast ten wf © x goMo =N. o. o Nef > IL ° ° Tue Jue 5 0 s. i H_H2 ade ~~ NSE Joe N OAD Ne, > Sh I L ° ° le Jus H AON S—_, SN _ h > 5 = “odo ont ° > SCT © ° 5 Ws Ong s i Pp AON ~~. “N= 0 NOX NN N goo x x ° wed “ Ne” > Cn wT o o Ws 0. 0. s. Ho AOA ~~ i NN gd from 0 o he OL i, > CC oe o o < ENASNASA AN > ws J o AOA, s. _ Oo VO STN N pe x Xx ° MeN, o Nef! > Cn OG ° ° Ws SOM H Omg OS AAS _ 5 NTC ywwearCBA p x Y G ot f i ~ = r N OMe MeO’ N, ° 0 ? uy OM i HONG LW Sv=¢ CBA w I x © ! =N, ©. 0. Ney CC ° 0 7 we SOM fi s. Ae ~S “if CBA “en a A, N Me MeO N. 0 o J ws SOM i Argus a, Peng Na. on XT Y OWTE < A oN Deo: MeO’ : rN 0 / Ws ONO HIN ANN a i X ho Dab ’ N. N—, 0. 0. 3 N OMe MeO N, | 0 0 Ws > ee NTN i ie % x bs 2. New r Co MeO N. § 7 * Ws 0. 0 s. fc CBA Og INC Ne NTN T Xx Yet Sel iy N Ne, o o 5 N OMe MeO’ N, | ° 0° * Wg 0. 0. s Rc CBA INN —! Pa ~NC NTE x X iQ Xx =N. Oy oN Y X i N- OMe now | 0 o o wg N—C: CBA A Be “ No —H x om © eh Os A ” 3 N ‘OMe MeO N, L 0 o We " oo Ws f fom N— CBA Gl ila NN =G X X com © Yen Ls Neer? r Fe od | ° ° Wi Wg R H PONISI NY Sy oe ona = N. 0. 0. N—, % { $ J We ~ he Ws o R { i p NENT NN fl sts xX x, com © Yen. La Nett > oon ee 6 we oo oo Ws. AON Oy Se A AN=G CBA ; x z Yon o o. ie, CCC | o ° Cw 5 >= Nx ws 0 AON NAO S\ ASO _N=—C CBA - x ¥ . N H | LY Wen o o. Ney TI, ° o , | Ws > x Ws Lk ONO SS AN AN Goren CBA 5 2 : 2. N oN o o i Com wo sor o H POA IN NN A x x B | LH pe oa Neg Ken a 0 0 | 2 Ws TN 0 i = oe td a or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when it is a single bond, X is -H; and Y is -OH or - SOsM. In certain embodiments, the double line == between N and C represents a double bond, X is absent and Y is -H. In certain embodiments, the double line == between N and C represents a single bond, X is -Hand Y is -SO:M. In certain embodiments, M is H*, Na* or K*. Another aspect of the invention provides an immunoconjugate having the following formula: 3 —cv) cea Js lL. wherein: CBA is the antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to the Jes’ group; Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of the invention, or the polypeptide thereof of the invention, and an aldehyde reactive group on Cy*3, and is represented by the following formula: HH f°. H EN 2 baaiaiianiadaias Bid dt fl shinai aiiaibe’ aiiatingd’ SIRE Shiite bur lietl data atta dail "Rl cpt AR Sh 0 HH O Ho H —C=N< —C —N«, 81§—C=N. s13—C —N- = §=N Ne. stf-5%- NV f H nN $2 t Nfs2. Hy H B “Ao, r Hz si? A Ne=N c=N~o H i 2, or wherein s1 is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy*3; Cy* is represented by the following formula: wherein: m’is1or2; R; and Ry, are each independently H or a (C;-Cs)alkyl; L, is represented by the following formula: Ras. Rye 3 sd Zg, s r s3 2 s Rez Rat wherein: s3 is the site covalently linked to the group Jes’; s4 is the site covalently linked to the -S- group on Cy; Za» is absent, -C(=0)-NRg-, or -NRy-C(=0)-; Ry is -H or a (C;-Cs)alkyl; Q is H, a charged substituent or an ionizable group; Rai, Raz, Ras, Rag, for each occurrence, are independently H or a (C1-Ca)alkyl; and ql and rl are each independently an integer from 0 to 10, provided that q1 and rl are not both 0. In certain embodiments, m’ is 1 and R; and Ry are both H. In certain embodiments, nr is 2 and R; and R» are both Me. In certain embodiments, -L,- is represented by the following formula: H 2? com sw AL 4. 5 Ans 4. s3 Lo s u NN 4. MOS nH R 3 vo RB Aen 4 ° SM Ane nN oe mn 0 sor o or a pharmaceutically acceptable salt thereof, wherein R is H or -SO3M and M is H™ or a cation. In certain embodiments, the immunoconjugate is represented by the following formula: anti, Sse s Hn | ws. 3 canton RN Arig Hn | H Jus, op A | OM Jo J wg. 2 DM | f LL ; coA-on,- y ~ dws. > o of A I NG CBA. G o H oBad-g—N., PN AS ou J W 1 ws, x on EE | pion oa I O,H J ws, or a pharmaceutically acceptable salt thereof; wherein DM is represented by the following formula: Me, \ SN 0 Nt 0 A Cl \ V MeO, AARL, ’ CN Y Ao SESE ny ved Hd N o Another aspect of the invention provides an immunoconjugate having the following formula: oases —or*) 'S wherein: CBA is the antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to the Jes’ group, Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of the invention, or the polypeptide thereof of the invention, and an aldehyde reactive group on Cy and is represented by the following formula: 0 Hy, H 2B gy 2 st3—C a's 2, 0 FN Ve, stig N HH O s13—C ve, : sie sis H Ne=N<, Se-Neg_ C=’ — Oo ¢=No } 2.0 5% } $2 wherein s1 is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy; Cy* is represented by the following formula: NN o Nt oO 0 8 TA - Aa, rN Y A 0 SEAN A om oN? 0 L,’ is represented by the following formula: 83 $—2, Zz s4 § "Se wh Rei Ry © . sor SR—12,. Ei _—F2 Zy, 2 s4 nt P m1 J Ry3 Rug Res Res © wherein: s3 is the site covalently linked to the group Jes’ group; s4 is the site covalently linked to -NMe- group on Cy; Zp) and Zp; are both absent, or one of Zs; and Zs; is absent and the other is - CH,-0- or -O-CH;-; Zp)’ and Zp’ are each independently absent, -CH;-O-, -O-CHz-, -NRg-C(=0)- CH;-, or -CH;-C(=0)-NRg-; Ry is H or (C;-Ca)alkyl; nl and m1 are each independently an integer from 1 to 6; one of E; and E; is -C(=0)-, and the other is -NRy-; or one of E; and E is - C(=0)- or -NRy-, and the other is absent; P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues; and Ro1, Rb2, Ros, Ros, Ros and Rus, for each occurrence, are each independently H ora (C;-Cs)alkyl. In certain embodiments, Roi, Rb2, Rb3, Ros, Rus, and Reg are all H. In certain embodiments, Ro is H. In certain embodiments, Zp,’ and Zp,’ are both absent; or Zy;’ is -CH,-O-; and Zp,’ is absent; or Zp,’ is -CH2-C(=0)-NRo-; and Zs,’ is -O-CHa- or absent. In certain embodiments, P is a peptide containing 2 to 5 amino acid residues. For example, P may be selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°- nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala- Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe- Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In certain embodiments, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, and D-Ala-D-Ala. In certain embodiments, immunoconjugate is represented by the following formula: : oy mi A CB G N J OY go 0 coA-fon; Ney om H Jw. 0 caa—con ~, i Js to~ A, | | a candy An fom | Jug o H H H Cl Hy—I N BS DM sao i LA ~~ ~~ | H 0 H 0 oO J ws, sanction, Joo I HE rng, wo Jus, santo, So 2 HL ~ us, oBAg—G=N.,, Aimed AT A ~™ | ‘ws. CBA: a Nr, AN JA BN TH YOY YY d DM Jus, DM | ¥ N. Gg ro SS Btn Y My H oy H, sso Jus. ; i J 1X Sti i N HN om} oY WY SAE Ju, LJ, ont, A y Di ws. 3 cand, op | oO “us, H Ey | us, or a pharmaceutically acceptable salt thereof, wherein DM is represented by the following structural formula: Me Xo \ 0 Nt 0 MX Cl \ 1 MeO, IAAL : MN SEAN x aS ved HS N o Another aspect of the invention provides an immunoconjugate represented by the following formula: ca{—cy®! ),, wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to Cy*! through a cysteine residue; Wcislor2; Cy©! is represented by the following formula: Rs PN (CRaRo)m Lo} N YT YX =N, 0. o. IN, oO oO . Reap CPi te v % o o i X Y. N. o o N=, oO 0 1 R2 wo ¢—to} o 2 r HN—. -N, o. o. “ N. LT LAD ° o 3 oO — 1 oF RA wel o YX Xx x 7 \ =N, o. o. N= N: o oO or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SOsM, and M is H* or a cation; Rsis -H or a (C1-Cs)alkyl; P is an amino acid residue or a peptide containing 2 to 20 amino acid residues; Ra and Rs, for each occurrence, are independently -H, (C1-Cs)alkyl, or a charged substituent or an ionizable group Q; W’ is -NR¢, R® is -(CH2-CH2-O)s-R¥; n is an integer from 2 to 6; Ris -H or -Me; R* is a (C-Cs)alkyl; and, RM Q | ) \ A ¥ st JN Rote © Lc is represented by Rage = , sl is the site covalently linked to CBA, and s2 is the site covalently linked to the -C(=0)- group on CyC!; wherein: Rig and Rao, for each occurrence, are independently -H or a (C;-Cs)alkyl; m” is an integer between 1 and 10; and R" is -H or a (C,-Cs)alkyl. In certain embodiments, R, and Ry, are both H; and Rs is H or Me. In certain embodiments, P is a peptide containing 2 to 5 amino acid residues. For example, P may be selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N’- nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala- Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe- Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In certain embodiments, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In certain embodiments, Q is -SO3M. In certain embodiments, Rig and Ryo are both H; and m” is an integer from 1 to 6. In certain embodiments, -Lc- is represented by the following formula: 0 2 “A st d In certain embodiments, the immunoconjugate is represented by the following formula: < PNA NSE > o o o Ari SaMACBA GS nA Jw < PINSON OAS > AAAS an (phar Donde LT GF A > we ogo x ° o en el L-, > om ty 2 res ° J Swe sor 0, H ogy Ane x A 0 yy bh commer 1 ° x YN 0. 0. New” Ney : OMe MeO’ > So o o wg or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or - SOM. Another aspect of the invention provides an immunoconjugate represented by the following formula: ceA-{—cy2 \, wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to Cy“? through a cysteine residue; Wcislor2; Cy? is represented by the following formula: xX Q Ss Re SRE Sie N x = o. o HN—, o o x AN x o 8 re PR 1 N YX X 7 \ h, 4 = Nel ! N. ° ° RZ ws Y. Xx =N, 0. o. hs, on CAD oO oO To o ° oo ,or RZ ws} y X AN = =N. OL. N=, N Ne x I - WC 0 0 or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1- Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is - OH or -SO:M, and M is H" or a cation; R*! is a (C)-Cs)alkyl; Reis -H or a (C1-Cs)alkyl; W’ is -NR¢"; R® is -(CH-CH;-0)1-R%; nis an integer from 2 to 6; Rk is -H or -Me; R* is a (C1-Co)alkyl; Lc’ is represented by the following formula: N y. Rig Riz , r 828, Pr vill st : "a hoc 0 oO fi Q 0 A Apt, x RE 2 Roo Roy Ry Rie 2: wherein: s1 is the site covalently linked to the CBA and s2 is the site covalently linked to -S- group on CyC2; Z is -C(=0)-NRgy-,0r -NRg-C(=0)-; Q is -H, a charged substituent, or an ionizable group; Ry, Rio, Ri, Riz, Ris, Rig, Roo, R21 and Raa, for each occurrence, are independently -H or a (C1-C3)alkyl; q and r, for each occurrence, are independently an integer between 0 and 10; m and n are each independently an integer between 0 and 10; R" is -H or a (Ci-Cs)alkyl; and P’ is an amino acid residue or a peptide containing 2 to 20 amino acid residues. In certain embodiments, P’ is a peptide containing 2 to S amino acid residues. For example, P’ may be selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe- Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe- NP-nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val- Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly- Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D- Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg- D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In certain embodiments, P’ is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In certain embodiments, in the immunoconjugate -Lc’- is represented by the following formula: 0 0 st vos 0 "som Ya 0 o Jus Y x ~y Ye. 0 Ao So Jt JL 8 N. N. Yr rrr riae 0’ In certain embodiments, R® is H or Me; R*! is -(CHa)p-(CR'RE)-, and R*®? is -(CHa)p- (CR'RY)-, wherein Rf and R# are each independently -H or a (C;-Cs)alkyl; and pis 0, 1, 2 or 3. In certain embodiments, Rf and Re are the same or different, and are selected from -H and -Me. In certain embodiments, the immunoconjugate is represented by the following formula: > 0 2 2 SOMpy o Py N. WY perp OY sepecon H 7m x x d N 0, NO N==t, > {RC ° ° > oO J We 2 2 SOM 0 WY SOA eden % 0 x x x d YJ -N Loo N= 5 WC 0 0 H my X > oO J we o < i 0 WY STI secon o N Ln Sod! ¢ i on FAD ” o o 0 Awe 0 5 Hon Hy £8 TY N sf-con vy. X x x [of -N 0. Oo ANH “ l 0 0 we 0 H 0. 0, s. N ANNO ~. I~ A ; OXY en Yl H ~~ N, 0. 0. N— 0’ 3 Cn A 0 Jw, “ 9 AON Oy Bey LUNN A . ~~ TY N efron Y, J X oy I~ N. 0. o Nes ¢ “ fe C wt oe o o Su SOM yam Tn o o. o s N OA ~C Sey A socaa x 0 A H 7 =N o o. N, - » EG ot wr C * | 0 o Au, sor SoM > TT 0 o o s. { AON Oy ~~. AY ~ A ~~ 3 N sejcaa vy, ¥ x ° py NY =N. 0. 0. Nes 0 5 N—( : OMe MeO’ io” | o 0 we or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or - SOM. In certain embodiments, the double line == between N and C represents a double bond, X is absent and Y is -H. In certain embodiments, the double line == between N and C represents a single bond, X is -H and Y is -SOsM. In certain embodiments, M is H", Na* or K*. Another aspect of the invention provides an immunoconjugate having the following formula: ceAH{—cy® )., wherein: CBA is an antibody or antigen-binding fragment thereof of the invention, or the polypeptide thereof of the invention, covalently linked to Cy“? through a cysteine residue; Wcis1lor2; Cy©3 is represented by the following formula: nv I ICPIGOLIIICU DY LUG 10110W He 10111 Qo WN s > ~ ot rey Lg] a 9 3X ° KR MeO, MAR . © Ao SENN Med Ha N o wherein: m’is 1 or2; R; and Ry, are each independently -H or a (C1-Cs)alkyl; Lc’ is represented by the following formula: 0, Ris Riz Nam) 24 Bhp? Nd st Fehr Q 11R10 O _ Co o fn [e} 0 on Nt, 5 N p X 2 Ry, Ry Ry, Rie hb wherein: sl is the site covalently linked to the CBA and s2 is the site covalently linked to -S- group on Cy©<3; Z is -C(=0)-NRg-,or -NRg-C(=0)-; Q is H, a charged substituent, or an ionizable group; Ry, Rio, Ri, Riz, Ris, Rig, Roo, R21 and Raa, for each occurrence, are independently -H or a (C1-C3)alkyl; q and r, for each occurrence, are independently an integer between 0 and 10; m and n are each independently an integer between 0 and 10; R" is -H or a (Ci-Cs)alkyl; and P’ is an amino acid residue or a peptide containing 2 to 20 amino acid residues. In certain embodiments, P’ is a peptide containing 2 to 5S amino acid residues. For example, P’ is selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Lle-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°- nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala- Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe- Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In certain embodiments, P’ is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In certain embodiments, -L¢’- is represented by the following formula: 2 o purging, Ho Som : 0 o s1 rho dsy 0 H 2. or AAT 2 wherein M is H* or a cation. In certain embodiments, m’ is 1 and R; and R; are both H. In certain embodiments, m’ is 2 and R; and R» are both Me. In certain embodiments, the immunoconjugate is represented by the following formula: 5 om ~~ Ln CBAs 1 we. con fu pfu Je or 90, ou o elon J J Eo | ° o 0 ye. or a pharmaceutically acceptable salt thereof, wherein DM is a drug moiety represented by the following formula: Nt vr ~ MeO HO H Another aspect of the invention provides a pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of the invention, or the polypeptide of the invention, or the immunoconjugate of the invention, and a pharmaceutically acceptable carrier. Another aspect of the invention provides a method for inhibiting the growth of a cell expressing CD123, comprising contacting the cell with the antibody or antigen-binding fragment thereof of the invention, or the polypeptide of the invention, or the immunoconjugate of the invention, or the pharmaceutical composition of the invention. In certain embodiments, the cell is a tumor cell. In certain embodiments, the cell is a leukemia cell or a lymphoma cell. Another aspect of the invention provides a method for treating a subject having cancer, wherein cells of the cancer expresses CD123, the method comprising administering to said subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of the invention, or the polypeptide of the invention, or the immunoconjugate of the invention, or the pharmaceutical composition of the invention. In certain embodiments, the cancer or cell-proliferative disorder is leukemia or lymphoma. In certain embodiments, the cancer or cell-proliferative disorder is selected from the group consisting of: acute myeloid leukemia (AML); chronic myeloid leukemia (CML); acute lymphoblastic leukemia (ALL), including B-cell lineage acute lymphoblastic leukemia (B-ALL); chronic lymphocytic leukemia (CLL); hairy cell leukemia (HCL); myelodysplastic syndrome; basic plasmacytoid DC neoplasm (BPDCN) leukemia; non-Hodgkin lymphomas (NHL), including mantle cell lymphoma; and Hodgkin's leukemia (HL). In certain embodiments, the cancer is acute myeloid leukemia (AML). In certain embodiments, the cancer is B-cell acute lymphoblastic leukemia (B-ALL). Another aspect of the invention provides a method for treating a cell-proliferative disorder in a subject, wherein cells of the cell-proliferative disorder expresses CD123, the method comprising administering to said subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of the invention, or the polypeptide of the invention, or the immunoconjugate of the invention, or the pharmaceutical composition of the invention, in an amount sufficient to treat said cell-proliferative disorder. It is contemplated that any one embodiment described herein, including those described only in one aspect of the invention (but not in others or not repeated in others), and those described only in the Examples, can be combined with any one or more other embodiments of the invention, unless explicitly disclaimed or inapplicable. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows inhibition of IL-3-dependent proliferation of TF-1 cells by chimeric CD123-6 antibody (chCD123-6) and its CDR-grafted huCD123-6 antibodies (huCD123- 6Gv4.6 and huCD123-6Gv4.7). FIGs. 2A and 2B show that three murine anti-CD123 antibodies (muCD123-3, -6 and -14) inhibit IL-3 dependent proliferation of TF-1 cells at least as well as 7G3. FIG. 2A shows inhibition of TF-1 cells cultured in the presence of IL-3 (1 ng / mL) by the various anti-CD123 antibodies, including CD123-binding control antibodies 7G3, 6H6, and 9F5. FIG. 2B shows inhibition of TF-1 cells cultured in the presence of GM-CSF (2 ng / mL) by the same anti- CD123 antibodies. FIG. 3 shows that murine anti-CD123 antibodies muCD123-3, -6, and -14 inhibit IL-3 (1 ng / mL) dependent proliferation of TF-1 cells in a dose-dependent manner, and to a higher degree than the 7G3 antibody. muCD123-16 is a negative control anti-CD123 antibody that binds CD123 but does not inhibit IL-3-dependent proliferation of TF-1 cells. FIGs. 4A and 4B show that the murine muCD123-3, -6, and -14 antibodies have higher binding affinity to CD123-positive AML cells than that of the 7G3 antibody in CD123-expressing TF-1 (FIG. 4A) and HNT-34 (FIG. 4B) cells. FIGs. 5A and 5B show that chimeric anti-CD-123 antibodies chCD123-3, -6, and -14 retain high binding affinity of their murine counterparts, using either HNT-34 cells (FIG. 5A) or the CD123-positive acute myeloid leukemia (AML) cell line MOLM-13 (FIG. 5B). Chimeric antibody chKTI, which does not bind CD123, was included as negative control. FIG. 6 shows that the chimeric chCD123-3, -6, and -14 anti-CD-123 antibodies retain functional activity of their murine counterparts, as evidenced by their ability to inhibit IL-3 dependent proliferation of TF-1 cells. A non-functional chimeric anti-CD123 antibody (chCD123-18) that binds CD123 but does not inhibit IL-3-dependent proliferation of TF-1 cells was included as negative control. FIG. 7A shows that the murine (muCD123-6), chimeric (chCD123-6), and CDR- grafted huCD123-6 antibodies (huCD123-6Gv4.7S2 and huCD123-6Gv4.7S3) all have higher affinity than 7G3 to CD123-expressing HNT-34 cells. Chimeric antibody chKTI, which does not bind CD123, was included as negative control. FIGs. 7B and 7C show that conjugation of the huCD123-6Gv4.7S3 or the -Gv4.7 antibody to the D1 or D2 compounds through Lys-, Ser-, or Cys-linkage only moderately affected the binding affinities of these ADC conjugates, i.e., the Ser-linked huCD123-6Gv4.7S3-SeriMab-sD1 (see structure in FIG. 17) and huCD123-6Gv4.7S3-SeriMab-D8, and the Lys-linked huCD123-6Gv4.7S3-sSPDB- D1, and huCD123-6Gv4.7S3-D2 in FIG. 7B; and the Cys-linked huCD123-6Gv4.7-CysMab- D4 and huCD123-6Gv4.7-CysMab-D5 in FIG. 7C. In FIG. 7C, the unconjugated huCD123- 6Gv4.7 antibody has a heavy chain sequence of SEQ ID NO: 54, in which Xaa is Val. The conjugates with “S3-SeriMab” have cytotoxin (in this case, the indolinobenzodiazepine or “IGN” compounds herein after) linkage through oxidized N-terminal Ser on light chain. The conjugates with “CysMab” have cytotoxin (in this case, the IGN compounds) linkage through the engineered Cys in the heavy chain (i.e., the Cys corresponding to the 5% to the last Cys in SEQ ID NO: 54). FIG. 8A shows that the chimeric (chCD123-6) and CDR-grafted (huCD123- 6Gv4.7S2 and huCD123-6Gv4.7S3) huCD123-6 antibodies inhibit IL-3 dependent proliferation of TF-1 cells better than the 7G3 antibodies. The inhibition is IL-3 dependent, as these antibodies had no inhibitory effect when the cells were grown in the presence of GM-CSF (FIG. 8B). FIG. 9A shows expression constructs of IL-3Ra (CD123) extra-cellular domain and chimeric receptor proteins comprising IL-3Ra (gray) and GMRa domains (white). FIG. 9B shows that the CD123-6 antibody binds primarily to the CRM domain of IL-3Ra (residues 101-306). FIG. 9C shows that the CD123-3 antibody binds primarily to the CRM domain of IL-3Ra (residues 101-306). FIG. 9D shows that the CD123-14 antibody binds exclusively to the N-terminal domain of IL-3Ra (residues 1-100). FIG. 9E shows that the 7G3 antibody binds exclusively to the N-terminal domain of IL-3Ra (residues 1-100). FIG. 9F shows that the 6H6 antibody binds exclusively to the N-terminal domain of IL-3Ra (residues 1-100). FIG. 9G shows that the 9F5 antibody binds exclusively to the N-terminal domain of IL-3Ra (residues 1-100). FIG. 10 demonstrates that maytansinoid DM1 conjugate of the resurfaced huCD123- 6Rv1.1 antibody, huCD123-6Rv1.1-CX1-1-DM1, exhibits dose-dependent cytotoxicity on the growth factor-independent CD123-expressing AML cell line OCI-AML4. The cytotoxicity is CD123-dependent, as evidenced by the ability of excess unconjugated huCD123-6 antibody (500 nM) to block the cytotoxicity. FIG. 11A shows in vitro cytotoxicity of the various resurfaced lysine-linked huCD123-6Rv1.1-IGN conjugates on multiple CD123-positive malignant cell lines of different origin. FIG. 11B shows in vitro cytotoxicity of the various lysine- or cysteine-linked huCD123-6-IGN conjugates on multiple CD123-positive B-ALL cell lines. The non-binding KTI antibody based conjugates are included as negative controls. FIG. 11C shows that the various Lys- or Cys-linked IGN compounds are highly active on P-gp (P-glycoprotein) positive AML cell lines Kasumi-3 and MOLM-1. The control curves with open data points are produced in the presence of excess unconjugated matching huCD123 antibodies. FIG. 11D shows that nearly all of the various Lys- or Cys-linked CD123-IGN conjugates of the invention kill 90% of the AML progenitor cells from 9 AML patient samples at nM or sub-nM concentrations. FIG. 11E shows that the Cys-linked huCD123-6Gv4.7-CysMab-D35 conjugate kills normal blood cells at concentrations that are >100-fold higher than those needed to kill AML progenitors. In comparison, Mylotarg does not exhibit such preferential killing effect. FIGs. 12A and 12B show in vitro cytotoxicity of the various lysine-linked huCD123- 6Rv1.1-IGN conjugates on primary cells from AML patients. The result from a typical CFU assay for one primary patient sample is presented in FIG. 12A. FIG. 12B shows the ICs values for all AML patient samples treated with the conjugates. FIGs. 13A-13C show that the IGN conjugate of CysMab of huCD123-6 (huCD123- 6Gv4.6-CysMab-Ds5, filled black circle) is at least as active as the lysine-linked conjugate (huCD123-6Gv4.6-D2, filled black square) of the same antibody towards the AML cell line EOL-1 (FIG. 13A), the B-ALL cell line KOPN-8 (FIG. 13B), and the CML cell line MOLM- 1 (FIG. 13C). The dotted curves connecting open data points in each figure represent activity of the respective conjugates (i.e., open circle for huCD123-6Gv4.6-CysMab-D5, and open square for huCD123-6Gv4.6-D2) in the presence of blocking concentration (500 nM) of the unconjugated chCD123-6 antibody. FIGs. 14A-14C show that SeriMab of huCD123-6 (huCD123-6Rv1.1S2-SeriMab-D8, filled black circle) is at least as active as the lysine-linked conjugate (huCD123-6Rv1.1-D2, filled downward black triangle) of the same antibody in AML cell lines SHI-1 (FIG. 14A) and HNT-34 (FIG. 14B), as well as the CML cell line MOLM-1 (FIG. 14C). The dotted curves connecting open data points in each figure represent activity of the respective conjugates (i.e., open circle for huCD123-6Rv1.1S2-SeriMab-D8, and open downward triangle for huCD123-6Rv1.1-D2) in the presence of blocking concentration (500 nM) of the unconjugated huCD123-6 antibody. FIG. 15 shows a schematic drawing to show the general steps that can be used to synthesize a Ser-linkage conjugate of the invention. FIG. 16 shows a schematic drawing to show the general steps that can be used to synthesize a Ser-linkage conjugate of the invention. FIG. 17 shows a schematic drawing to show the general steps that can be used to synthesize a Ser-linkage conjugate of the invention. FIG. 18 shows that the Cys-linked huCD123-6Gv4.7-CysMab-D5 conjugate has higher activity than gemtuzumab ozogamicin (GO) (also known as Mylotarg) in unselected AML patient samples. FIG. 19 shows that the Cys-linked huCD123-6Gv4.7-CysMab-D5 conjugate kills normal progenitor cells at concentrations that are >100-fold higher than those needed to kill AML progenitors. In comparison, Mylotarg and huCD123-6G4.7-CysMab-D5’ (ADC of DNA cross-linker D5’) do not exhibit such preferential killing effect. FIG. 20 shows in vivo efficacy of CD123-IGN conjugates in the MV4-11 AML subcutaneous mice model. FIG. 21 shows that the Cys-linked huCD123-6Gv4.7-CysMab-D5 conjugate is highly active on various CD123-positive AML cell lines with poor prognostic factors. FIG. 22 shows in vivo bioluminescence imaging of mice treated with huCD123- 6Gv4.7-CysMab-D5 conjugate as compared to mice treated with vehicle and control on day 26. Treatment with the conjugate significantly reduces tumor burden in mice. FIG. 23 shows treatment with huCD123-6Gv4.7-CysMab-D5 conjugate extended survival in 6 / 6 mice as compared to mice treated with vehicle and control. FIG. 24 shows that the incubation of MV4-11 cells with huCD123-6Gv4.7-CysMab- D5 conjugate leads to DNA damage, arrest in S-phase of the cell cycle, and apoptosis- mediated cell death. FIG. 25 shows in vivo efficacy of CD123-IGN conjugates in the Molm-13 AML disseminated model. FIG. 26 shows in vivo efficacy of CD123-IGN conjugates in the EOL-1 subcutaneous model. FIG. 27 shows in vivo efficacy of huCD123-CysMab-D5 conjugate at various doses in the EOL-1 subcutaneous model. FIG. 28 shows in vivo efficacy of huCD123-CysMab-D5 conjugate compared to the corresponding free drug form of the payload (FGN849 or D5), naked antibody, control, cytarabine, and azacitidine in the EOL-1 subcutaenous model. FIG. 29 shows in vivo efficacy of CD123-IGN conjugates in the MV4-11 AML disseminated model. FIG. 30 shows in vivo efficacy of CD123-IGN conjugates in the MV4-11 AML subcutaneous model. FIG 31 shows treatment with huCD123-CysMab-D5 conjugate extended survival in mice as compared to mice treated with vehicle and control. FIG. 32 shows in vivo tolerability of huCD123-CysMab-D5 and huCD123-SeriMab- sD1 conjugates in mice. FIG. 33 shows in vivo tolerability of huCD123-lysine linked-D2 conjugate in mice. DETAILED DESCRIPTION OF THE INVENTION 1. Definitions To facilitate an understanding of the present invention, a number of terms and phrases are defined below. The terms “(human) IL-3Ra,” “Interleukine-3 Receptor alpha,” or “CD123,” as used interchangeably herein, refers to any native (human) IL-3Ra or CD123, unless otherwise indicated. The CD123 protein is an interleukin 3-specific subunit of a heterodimeric cytokine receptor (IL-3 Receptor, or IL-3R). The IL-3R is comprised of a ligand specific alpha subunit, and a signal transducing common beta subunit (also known as CD131) shared by the receptors for interleukin 3 (IL3), colony stimulating factor 2 (CSF2 / GM-CSF), and interleukin 5 (IL5). The binding of CD123 / IL-3Ra to IL3 depends on the beta subunit. The beta subunit is activated by the ligand binding, and is required for the biological activities of 113. All of these above terms for CD123 can refer to either a protein or nucleic acid sequence as indicated herein. The term “CD123 / IL-3Ra” encompasses “full-length,” unprocessed CD123 / IL-3Ra, as well as any form of CD123 / IL-3Ra that results from processing within the cell. The term also encompasses naturally occurring variants of CD123 / IL-3Ra protein or nucleic acid, e.g., splice variants, allelic variants and isoforms. The CD123 / IL-3Ra polypeptides and polynucleotides described herein can be isolated from a variety of sources, such as from human tissue types or from another source, or prepared by recombinant or synthetic methods. Examples of CD123 / IL-3Ra sequences include, but are not limited to NCBI reference numbers NP_002174 & NM_002183 (protein and nucleic acid sequences for human CD123 variant 1), and NP_001254642 & NM_001267713 (protein and nucleic acid sequences for human CD123 variant 2). The term “antibody” means an immunoglobulin molecule that recognizes and specifically binds to a target, such as a protein, polypeptide, peptide, carbohydrate, polynucleotide, lipid, or combinations of the foregoing through at least one antigen recognition site within the variable region of the immunoglobulin molecule. As used herein, the term “antibody” encompasses intact polyclonal antibodies, intact monoclonal antibodies, antibody fragments (such as Fab, Fab’, F(ab’), and Fv fragments), single chain Fv (scFv) mutants, multispecific antibodies such as bispecific antibodies, chimeric antibodies, humanized antibodies, human antibodies, fusion proteins comprising an antigen determination portion of an antibody, and any other modified immunoglobulin molecule comprising an antigen recognition site so long as the antibodies exhibit the desired biological activity. An antibody can be of any of the five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, or subclasses (isotypes) thereof (e.g., IgG1, 1gG2, 1gG3, IgG4, IgAl and IgA2), based on the identity of their heavy-chain constant domains referred to as alpha, delta, epsilon, gamma, and mu, respectively. The different classes of immunoglobulins have different and well known subunit structures and three-dimensional configurations. Antibodies can be naked or conjugated to other molecules such as toxins, radioisotopes, etc. In some embodiments, an antibody is a non-naturally occurring antibody. In some embodiments, an antibody is purified from natural components. In some embodiments, an antibody is recombinantly produced. In some embodiments, an antibody is produced by a hybridoma. A “blocking” antibody or an “antagonist” antibody is one which inhibits or reduces biological activity of the antigen it binds, such as CD123 / IL-3Ra. In a certain embodiment, blocking antibodies or antagonist antibodies substantially or completely inhibit the biological activity of the antigen. Desirably, the biological activity is reduced by 10%, 20%, 30%, 50%, 70%, 80%, 90%, 95%, or even 100%. The term “anti-CD123 antibody,” “anti-IL-3Ra antibody” or “an antibody that (specifically) binds to CD123 / IL-3Ra” refers to an antibody that is capable of binding CD123 / IL-3Ra with sufficient affinity such that the antibody is useful as a diagnostic and / or therapeutic agent in targeting CD123 / IL-3Ra. Unless otherwise specified, the extent of binding of an anti-CD123 / IL-3Ra antibody to an unrelated, non-CD123 / IL-3Ra protein is less than about 10% of the binding of the antibody to CD123 / IL-3Ra as measured, e.g., by a radioimmunoassay (RIA). In certain embodiments, an antibody that binds to CD123 / IL-3Ra has a dissociation constant (Kg) of <0.5 nM, <0.3 nM, <0.1 nM, <0.05 nM, or <0.01 nM. In one embodiment, the anti-CD123 / IL-3Ra antibody does not bind the common beta chain CD131. In one embodiment, the anti-CD123 / IL-3Ra antibody does not bind to the same epitope of CD123 that is bound by the known and commercially available CD123 antibodies such as 7G3 (mouse IgG2a), 6H6 (mouse IgG), and 9F5 (mouse IgG1) (Sun et al., Blood 87(1): 83-92, 1996). The sequences of anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof of the invention are provided in Tables 1-6 below. The nomenclature for the various antibodies and immuno-conjugates of the invention are provided separately below. The term “antibody fragment” refers to a portion of an intact antibody and refers to the antigenic determining variable regions of an intact antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab’, F(ab’),, and Fy fragments, linear antibodies, single chain antibodies, and multispecific antibodies formed from antibody fragments. The term “antigen-binding fragment” of an antibody includes one or more fragments of an antibody that retain the ability to specifically bind to an antigen. It has been shown that the antigen-binding function of an antibody can be performed by certain fragments of a full-length antibody. Examples of binding fragments encompassed within the term “antigen-binding fragment” of an antibody include (without limitation): (i) an Fab fragment, a monovalent fragment consisting of the Vi, Vu, Ct, and Cai domains (e.g., an antibody digested by papain yields three fragments: two antigen-binding Fab fragments, and one Fc fragment that does not bind antigen); (ii) a F(ab’), fragment, a bivalent fragment comprising two Fab fragments linked by a disulfide bridge at the hinge region (e.g., an antibody digested by pepsin yields two fragments: a bivalent antigen-binding F(ab’)2 fragment, and a pFc’ fragment that does not bind antigen) and its related F(ab’) monovalent unit; (iii) a Fq fragment consisting of the Vi and Cy: domains (i.e., that portion of the heavy chain which is included in the Fab); (iv) a F, fragment consisting of the V1 and Vg domains of a single arm of an antibody, and the related disulfide linked Fy; (v) a dAb (domain antibody) or sdAb (single domain antibody) fragment (Ward ez al., Nature 341:544-546, 1989), which consists of a Va domain; and (vi) an isolated complementarity determining region (CDR). A “monoclonal antibody” refers to a homogeneous antibody population involved in the highly specific recognition and binding of a single antigenic determinant, or epitope. This is in contrast to polyclonal antibodies that typically include different antibodies directed against different antigenic determinants. The term “monoclonal antibody” encompasses both intact and full-length monoclonal antibodies as well as antibody fragments (such as Fab, Fab’, F(ab’), Fv), single chain (scFv) mutants, fusion proteins comprising an antibody portion, and any other modified immunoglobulin molecule comprising an antigen recognition site. Furthermore, “monoclonal antibody” refers to such antibodies made in any number of manners including but not limited to by hybridoma, phage selection, recombinant expression, and transgenic animals. The term “humanized antibody” refers to forms of non-human (e.g., murine) antibodies that are specific immunoglobulin chains, chimeric immunoglobulins, or fragments thereof that contain minimal non-human (e.g., murine) sequences. Typically, humanized antibodies are human immunoglobulins in which residues from the complementary determining region (CDR) are replaced by residues from the CDR of a non-human species (e.g., mouse, rat, rabbit, hamster) that have the desired specificity, affinity, and capability (Jones et al., Nature 321:522-525, 1986; Riechmann et al., Nature 332:323-327, 1988; Verhoeyen et al., Science 239:1534-1536, 1988). In some instances, the Fy framework region (FR) residues of a human immunoglobulin are replaced with the corresponding residues in an antibody from a non- human species that has the desired specificity, affinity, and capability. The humanized antibody can be further modified by the substitution of additional residues either in the Fy framework region and / or within the replaced non-human residues to refine and optimize antibody specificity, affinity, and / or capability. In general, the humanized antibody will comprise substantially all of at least one, and typically two or three, variable domains containing all or substantially all of the CDR regions that correspond to the non-human immunoglobulin whereas all or substantially all of the FR regions are those of a human immunoglobulin consensus sequence. The humanized antibody can also comprise at least a portion of an immunoglobulin constant region or domain (Fc), typically that of a human immunoglobulin. Examples of methods used to generate humanized antibodies are described in U.S. Pats. 5,225,539 and 5,639,641, Roguska et al., Proc. Natl. Acad. Sci. USA 91(3):969- 973, 1994; and Roguska et al., Protein Eng. 9(10):895-904, 1996 (all incorporated herein by reference). In some embodiments, a “humanized antibody” is a resurfaced antibody. In some embodiments, a “humanized antibody” is a CDR-grafted antibody. A “variable region” of an antibody refers to the variable region of the antibody light chain or the variable region of the antibody heavy chain, either alone or in combination. The variable regions of the heavy and light chain each consist of four framework regions (FR) connected by three complementarity determining regions (CDRs) also known as hypervariable regions. The CDRs in each chain are held together in close proximity by the FRs and, with the CDRs from the other chain, contribute to the formation of the antigen- binding site of antibodies. There are at least two techniques for determining CDRs: (1) an approach based on cross-species sequence variability (i.e., Kabat et al. Sequences of Proteins of Immunological Interest, 5th ed., 1991, National Institutes of Health, Bethesda Md.); and (2) an approach based on crystallographic studies of antigen-antibody complexes (Al-lazikani et al., J. Molec. Biol. 273:927-948, 1997). In addition, combinations of these two approaches are sometimes used in the art to determine CDRs. The Kabat numbering system is generally used when referring to a residue in the variable domain (approximately residues 1-107 of the light chain and residues 1-113 of the heavy chain) (e.g., Kabat et al., Sequences of Immunological Interest, 5th Ed., Public Health Service, National Institutes of Health, Bethesda, Md. (1991)). The amino acid position numbering as in Kabat, refers to the numbering system used for heavy chain variable domains or light chain variable domains of the compilation of antibodies in Kabat ez al., Sequences of Proteins of Immunological Interest, 5th Ed., Public Health Service, National Institutes of Health, Bethesda, Md. (1991) (incorporated herein by reference). Using this numbering system, the actual linear amino acid sequence can contain fewer or additional amino acids corresponding to a shortening of, or insertion into, a FR or CDR of the variable domain. For example, a heavy chain variable domain can include a single amino acid insert (residue 52a according to Kabat) after residue 52 of H2 and inserted residues (e.g., residues 82a, 82b, and 82c, ezc. according to Kabat) after heavy chain FR residue 82. The Kabat numbering of residues can be determined for a given antibody by alignment at regions of homology of the sequence of the antibody with a “standard” Kabat numbered sequence. Chothia refers instead to the location of the structural loops (Chothia and Lesk, J. Mol. Biol. 196:901-917,1987). The end of the Chothia CDR-H1 loop when numbered using the Kabat numbering convention varies between H32 and H34 depending on the length of the loop. This is because the Kabat numbering scheme places the insertions at H35A and H35B - if neither 35A nor 35B is present, the loop ends at 32; if only 35A is present, the loop ends at 33; if both 35A and 35B are present, the loop ends at 34. The AbM hypervariable regions represent a compromise between the Kabat CDRs and Chothia structural loops, and are used by Oxford Molecular’s AbM antibody modeling software. Hl H31-H35B H26-H35B H26-H32..34 (Kabat Numbering) Hl H31-H35 H26-H35 H26-H32 (Chothia Numbering) H2 HS50-H65 HS50-HS8 HS52-HS56 H3 H9S-H102 H95-H102 H95-H102 The term “human antibody” means an antibody produced by a human or an antibody having an amino acid sequence corresponding to an antibody produced by a human made using any technique known in the art. In certain embodiments, the human antibody does not have non-human sequence. This definition of a human antibody includes intact or full-length antibodies, or antigen-binding fragments thereof. The term “chimeric antibodies” refers to antibodies wherein the amino acid sequence of the immunoglobulin molecule is derived from two or more species. Typically, the variable region of both light and heavy chains corresponds to the variable region of antibodies derived from one species of mammals (e.g., mouse, rat, rabbit, etc.) with the desired specificity, affinity, and capability while the constant regions are homologous to the sequences in antibodies derived from another (usually human) to avoid or reduce the chance of eliciting an immune response in that species (e.g., human). In certain embodiments, chimeric antibody may include an antibody or antigen-binding fragment thereof comprising at least one human heavy and / or light chain polypeptide, such as, for example, an antibody comprising murine light chain and human heavy chain polypeptides. The terms “epitope” or “antigenic determinant” are used interchangeably herein and refer to that portion of an antigen capable of being recognized and specifically bound by a particular antibody. When the antigen is a polypeptide, epitopes can be formed both from contiguous amino acids and noncontiguous amino acids juxtaposed by tertiary folding of a protein. Epitopes formed from contiguous amino acids are typically retained upon protein denaturing, whereas epitopes formed by tertiary folding are typically lost upon protein denaturing. An epitope typically includes at least 3, and more usually, at least 5 or 8-10 amino acids in a unique spatial conformation. “Binding affinity” generally refers to the strength of the sum total of noncovalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (Kg) or the half-maximal effective concentration (ECso). Affinity can be measured by common methods known in the art, including those described herein. Low-affinity antibodies generally bind antigen slowly and tend to dissociate readily, whereas high-affinity antibodies generally bind antigen faster and tend to remain bound longer. A variety of methods of measuring binding affinity are known in the art, any of which can be used for purposes of the present invention. Specific illustrative embodiments are described herein. “Or better” when used herein to refer to binding affinity refers to a stronger binding between a molecule and its binding partner. “Or better” when used herein refers to a stronger binding, represented by a smaller numerical Ka value. For example, an antibody which has an affinity for an antigen of “0.3 nM or better,” the antibody’s affinity for the antigen is <0.3 nM, e.g., 0.29 nM, 0.28 nM, 0.27 nM erc., or any value equal to or less than 0.3 nM. In one embodiment, the antibody’s affinity as determined by a Ks will be between about 102 to about 10-12 M, between about 106 to about 10-1 ! M, between about 106 to about 10-10 M, between about 106 to about 10° M, between about 10° to about 10-® M, or between about 10° 6 to about 107 M. By “specifically binds,” it is generally meant that an antibody binds to an epitope via its antigen-binding domain, and that the binding entails some complementarity between the antigen-binding domain and the epitope. According to this definition, an antibody is said to “specifically bind” to an epitope when it binds to that epitope, via its antigen-binding domain more readily than it would bind to a random, unrelated epitope. The term “specificity” is used herein to qualify the relative affinity by which a certain antibody binds to a certain epitope. For example, antibody “A” may be deemed to have a higher specificity for a given epitope than antibody “B,” or antibody “A” may be said to bind to epitope “C” with a higher specificity than it has for related epitope “D.” In certain embodiments, an antibody or antigen-binding fragment of the invention “specifically binds” to a CD123 antigen, in that it has a higher binding specificity to the CD123 antigen (from any species) than that to a non-CD123 antigen. In certain embodiments, an antibody or antigen-binding fragment of the invention “specifically binds” to a human CD123 antigen, in that it has a higher binding specificity to the human CD123 antigen than that to a non-human CD123 antigen (e.g., a mouse or a rat CD123). By “preferentially binds,” it is meant that the antibody specifically binds to an epitope more readily than it would bind to a related, similar, homologous, or analogous epitope. Thus, an antibody which “preferentially binds” to a given epitope would more likely bind to that epitope than to a related epitope, even though such an antibody may cross-react with the related epitope. For example, in certain embodiments, an antibody or antigen-binding fragment of the invention “preferentially binds” to a human CD123 antigen over a mouse CD123. An antibody is said to “competitively inhibit” binding of a reference antibody to a given epitope if it preferentially binds to that epitope to the extent that it blocks, to some degree, binding of the reference antibody to the epitope. Competitive inhibition may be determined by any method known in the art, for example, competition ELISA assays. An antibody may be said to competitively inhibit binding of the reference antibody to a given epitope by at least 90%, at least 80%, at least 70%, at least 60%, or at least 50%. The phrase “substantially similar,” or “substantially the same,” as used herein, denotes a sufficiently high degree of similarity between two numeric values (generally one associated with an antibody of the invention and the other associated with a reference / comparator antibody) such that one of skill in the art would consider the difference between the two values to be of little or no biological and / or statistical significance within the context of the biological characteristics measured by said values (e.g., Ka values). The difference between said two values is less than about 50%, less than about 40%, less than about 30%, less than about 20%, or less than about 10% as a function of the value for the reference / comparator antibody. A polypeptide, antibody, polynucleotide, vector, cell, or composition which is “isolated” is a polypeptide, antibody, polynucleotide, vector, cell, or composition which is in a form not found in nature. Isolated polypeptides, antibodies, polynucleotides, vectors, cells or compositions include those which have been purified to a degree that they are no longer in a form in which they are found in nature. In some embodiments, an antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure. As used herein, “substantially pure” refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure. The term “immunoconjugate,” “conjugate,” or “ADC” as used herein refers to a compound or a derivative thereof that is linked to a cell binding agent (i.e., an anti- CD123 / IL-3Ra antibody or fragment thereof) and is defined by a generic formula: A-L-C, wherein C = cytotoxin, L = linker, and A = cell binding agent (CBA), such as anti-CD123 / IL- 3Ra antibody or antibody fragment. Immunoconjugates can also be defined by the generic formula in reverse order: C-L-A. A “linker” is any chemical moiety that is capable of linking a compound, usually a drug, such as a cytotoxic agent described herein (e.g., maytansinoid or IGN (indolinobenzodiazepine) compounds), to a cell-binding agent such as an anti-CD123 / IL-3Ra antibody or a fragment thereof in a stable, covalent manner. Linkers can be susceptible to or be substantially resistant to acid-induced cleavage, light-induced cleavage, peptidase-induced cleavage, esterase-induced cleavage, and disulfide bond cleavage, at conditions under which the compound or the antibody remains active. Suitable linkers are well known in the art and include, for example, disulfide groups, thioether groups, acid labile groups, photolabile groups, peptidase labile groups and esterase labile groups. Linkers also include charged linkers, and hydrophilic forms thereof as described herein and know in the art. The terms “elevated” CD123 / IL-3Ra, “increased expression” of CD123 / IL-3Ra and “overexpression” of CD123 / IL-3Ra refer to a sample which contains elevated levels of CD123 expression. The CD123 can be elevated, increased, or overexpressed as compared to a control value (e.g., expression level in a biological sample, tissue, or cell from a subject without cancer, a sample or cancer known to express no or low CD123 / IL-3Ra, a normal sample, or a cancer that does not have elevated CD123 / IL-3Ra values). For example, a sample (e.g., one from a hematological cancer such as leukemia and lymphoma) with increased expression can contain an increase of at least 2-, 3, 4-, 5-, 10-, 15-, 20-, 25-, 30-, or at least 50-fold relative to a control / normal values. A “reference sample” can be used to correlate and compare the results obtained in the methods of the invention from a test sample. Reference samples can be cells (e.g., cell lines, cell pellets) or tissue. The CD123 / IL-3Ra levels in the “reference sample” can be an absolute or relative amount, a range of amount, a minimum and / or maximum amount, a mean amount, and / or a median amount of CD123 / IL-3Ra. A “reference sample” can also serve as a baseline of CD123 / IL-3Ra expression to which the test sample is compared. The “reference sample” can include a prior sample or baseline sample from the same patient, a normal reference with a known level of CD123 / IL-3Ra expression, or a reference from a relevant patient population with a known level of CD123 / IL-3Ra expression. CD123 / IL-3Ra levels can also be expressed as values in a standard curve. A standard curve is a quantitative method of plotting assay data to determine the concentration of CD123 / IL-3Ra in a sample. In one embodiment, a reference sample is an antigen standard comprising purified CD123 / IL- 3Ra. The diagnostic methods of the invention can involve a comparison between expression levels of CD123 / IL-3Ra in a test sample and a “reference value.” In some embodiments, the reference value is the expression level of the CD123 / IL-3Ra in a reference sample. A reference value can be a predetermined value and can also be determined from reference samples (e.g., control biological samples or reference samples) tested in parallel with the test samples. A reference value can be a single cut-off value, such as a median or mean or a range of values, such as a confidence interval. Reference values can be established for various subgroups of individuals. The term “primary antibody” herein refers to an antibody that binds specifically to the target protein antigen in a sample. A primary antibody is generally the first antibody used in an ELISA assay or IHC procedure. In one embodiment, the primary antibody is the only antibody used in an IHC procedure. The term “secondary antibody” herein refers to an antibody that binds specifically to a primary antibody, thereby forming a bridge or link between the primary antibody and a subsequent reagent, if any. The secondary antibody is generally the second antibody used in an immunohistochemical procedure. A “sample” or “biological sample” of the present invention is of biological origin, in specific embodiments, such as from eukaryotic organisms. In some embodiments, the sample is a human sample, but animal samples may also be used. Non-limiting sources of a sample for use in the present invention include solid tissue, biopsy aspirates, ascites, fluidic extracts, blood, plasma, serum, spinal fluid, lymph fluid, the external sections of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, milk, tumors, organs, cell cultures and / or cell culture constituents, for example. A “cancerous sample” is a sample that contains a cancerous cell. The method can be used to examine an aspect of expression of CD123 / IL- 3Rao or a state of a sample, including, but not limited to, comparing different types of cells or tissues, comparing different developmental stages, and detecting or determining the presence and / or type of disease or abnormality. As used herein, the term “capture reagent” refers to a reagent capable of binding and capturing a target molecule in a sample such that under suitable condition, the capture reagent-target molecule complex can be separated from the rest of the sample. In one embodiment, the capture reagent is immobilized. In one embodiment, the capture reagent in a sandwich immunoassay is an antibody or a mixture of different antibodies against a target antigen. As used herein, the term “detectable antibody” refers to an antibody that is capable of being detected either directly through a label amplified by a detection means, or indirectly through, e.g., another antibody that is labeled. For direct labeling, the antibody is typically conjugated to a moiety that is detectable by some means. In one embodiment, the detectable antibody is a biotinylated antibody. As used herein, the term “detection means” refers to a moiety or technique used to detect the presence of the detectable antibody and includes detection agents that amplify the immobilized label such as label captured onto a microtiter plate. In one embodiment, the detection means is a fluorimetric detection agent such as avidin or streptavidin. Commonly a “sandwich ELISA” employs the following steps: (1) microtiter plate is coated with a capture antibody; (2) sample is added, and any antigen present binds to capture antibody; (3) detecting antibody is added and binds to antigen; (4) enzyme-linked secondary antibody is added and binds to detecting antibody; and (5) substrate is added and is converted by enzyme to detectable form. The word “label” when used herein refers to a detectable compound or composition which is conjugated directly or indirectly to the antibody so as to generate a “labeled” antibody. The label can be detectable by itself (e.g. radioisotope labels or fluorescent labels) or, in the case of an enzymatic label, can catalyze chemical alteration of a substrate compound or composition which is detectable. By “correlate” or “correlating” is meant comparing, in any way, the performance and / or results of a first analysis with the performance and / or results of a second analysis. For example, one may use the results of a first analysis in carrying out the second analysis and / or one may use the results of a first analysis to determine whether a second analysis should be performed and / or one may compare the results of a first analysis with the results of a second analysis. In one embodiment, increased expression of CD123 / IL-3Ra correlates with increased likelihood of effectiveness of a CD123 / IL-3Ra-targeting therapy. The terms “cancer” and “cancerous” refer to or describe the physiological condition in mammals in which a population of cells are characterized by unregulated cell growth. “Tumor” and “neoplasm” refer to one or more cells that result from excessive cell growth or proliferation, either benign (noncancerous) or malignant (cancerous) including pre-cancerous lesions. Examples of cancer include lymphoma and leukemia. Examples of cancer or tumorigenic diseases which can be treated and / or prevented by the methods and reagents (e.g., anti-CD123 antibody, antigen-binding fragment thereof, or immuno-conjugate thereof) of the invention include AML, CML, ALL (e.g., B-ALL), CLL, myelodysplastic syndrome, basic plasmacytoid DC neoplasm (BPDCN) leukemia, B-cell lymphomas including non- Hodgkin lymphomas (NHL), precursor B-cell lymphoblastic leukemia / lymphoma and mature B-cell neoplasms, such as B-cell chronic lymphocytic leukemia (B-CLL) / small lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, mantle cell lymphoma (MCL), follicular lymphoma (FL), including low-grade, intermediate-grade and high-grade FL, cutaneous follicle center lymphoma, marginal zone B- cell lymphoma (MALT type, nodal and splenic type), hairy cell leukemia (HCL), diffuse large B-cell lymphoma, Burkitt's lymphoma, plasmacytoma, plasma cell myeloma, post- transplant lymphoproliferative disorder, Waldenstrom's macroglobulinemia, anaplastic large- cell lymphoma (ALCL), and Hodgkin's leukemia (HL). Cancers also encompass cancers which contain cells having elevated CD123 / IL-3Ra expression levels. Such CD123 / IL-3Ra-elevated cancers include, but are not limited to, AML, CML, ALL (e.g., B-ALL), and CLL. The terms “cancer cell,” “tumor cell,” and grammatical equivalents refer to the total population of cells derived from a tumor or a pre-cancerous lesion, including both non- tumorigenic cells, which comprise the bulk of the tumor cell population, and tumorigenic stem cells (cancer stem cells). As used herein, the term “tumor cell” will be modified by the term “non-tumorigenic™ when referring solely to those tumor cells lacking the capacity to renew and differentiate to distinguish those tumor cells from cancer stem cells. The term “subject” refers to any animal (e.g., a mammal), including, but not limited to humans, non-human primates, rodents, and the like, which is to be the recipient of a particular treatment. Typically, the terms “subject” and “patient” are used interchangeably herein in reference to a human subject. Administration “in combination with” one or more further therapeutic agents includes simultaneous (concurrent) and consecutive administration in any order. The term “pharmaceutical formulation” refers to a preparation which is in such form as to permit the biological activity of the active ingredient to be effective, and which contains no additional components which are unacceptably toxic to a subject to which the formulation would be administered. Such formulation can be sterile. An “effective amount” of an antibody or immunoconjugate as disclosed herein is an amount sufficient to carry out a specifically stated purpose. An “effective amount” can be determined empirically and in a routine manner, in relation to the stated purpose. The term “therapeutically effective amount” refers to an amount of an antibody or other drug effective to “treat” a disease or disorder in a subject or mammal. In the case of cancer, the therapeutically effective amount of the drug can reduce the number of cancer cells; reduce the tumor size; inhibit (i.e., slow to some extent and in a certain embodiment, stop) cancer cell infiltration into peripheral organs; inhibit (i.e., slow to some extent and in a certain embodiment, stop) tumor metastasis; inhibit, to some extent, tumor growth; relieve to some extent one or more of the symptoms associated with the cancer; and / or result in a favorable response such as increased progression-free survival (PFS), disease-free survival (DFS), or overall survival (OS), complete response (CR), partial response (PR), or, in some cases, stable disease (SD), a decrease in progressive disease (PD), a reduced time to progression (TTP), or any combination thereof. See the definition herein of “treating.” To the extent the drug can prevent growth and / or kill existing cancer cells, it can be cytostatic and / or cytotoxic. A “prophylactically effective amount” refers to an amount effective, at dosages and for periods of time necessary, to achieve the desired prophylactic result. Typically but not necessarily, since a prophylactic dose is used in subjects prior to or at an earlier stage of disease, the prophylactically effective amount will be less than the therapeutically effective amount. The term “respond favorably” generally refers to causing a beneficial state in a subject. With respect to cancer treatment, the term refers to providing a therapeutic effect on the subject. Positive therapeutic effects in cancer can be measured in a number of ways (See, W.A. Weber, J. Nucl. Med. 50: 1S-10S (2009)). For example, tumor growth inhibition, molecular marker expression, serum marker expression, and molecular imaging techniques can all be used to assess therapeutic efficacy of an anti-cancer therapeutic. With respect to tumor growth inhibition, according to NCI standards, a T / C < 42% is the minimum level of anti-tumor activity. A T / C <10% is considered a high anti-tumor activity level, with T / C (%) = Median tumor volume of the treated / Median tumor volume of the control x 100. A favorable response can be assessed, for example, by increased progression-free survival (PFS), disease-free survival (DFS), or overall survival (OS), complete response (CR), partial response (PR), or, in some cases, stable disease (SD), a decrease in progressive disease (PD), a reduced time to progression (TTP), or any combination thereof. PFS, DFS, and OS can be measured by standards set by the National Cancer Institute and the U.S. Food and Drug Administration for the approval of new drugs. See Johnson er al., (2003) J. Clin. Oncol. 21(7): 1404-1411. “Progression free survival” (PFS) refers to the time from enrollment to disease progression or death. PFS is generally measured using the Kaplan-Meier method and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standards. Generally, progression free survival refers to the situation wherein a patient remains alive, without the cancer getting worse. A “complete response” or “complete remission” or “CR” indicates the disappearance of all signs of tumor or cancer in response to treatment. This does not always mean the cancer has been cured. A “partial response” or “PR” refers to a decrease in the size or volume of one or more tumors or lesions, or in the extent of cancer in the body, in response to treatment. “Stable disease” refers to disease without progression or relapse. In stable disease there is neither sufficient tumor shrinkage to qualify for partial response nor sufficient tumor increase to qualify as progressive disease. “Progressive disease” refers to the appearance of one more new lesions or tumors and / or the unequivocal progression of existing non-target lesions. Progressive disease can also refer to a tumor growth of more than 20 percent since treatment began, either due to an increases in mass or in spread of the tumor. “Disease free survival” (DFS) refers to the length of time during and after treatment that the patient remains free of disease. “Overall Survival” (OS) refers to the time from patient enrollment to death or censored at the date last known alive. OS includes a prolongation in life expectancy as compared to naive or untreated individuals or patients. Overall survival refers to the situation wherein a patient remains alive for a defined period of time, such as one year, five years, ezc., e.g., from the time of diagnosis or treatment. A “chemotherapeutic agent” is a chemical compound useful in the treatment of cancer, regardless of mechanism of action. Terms such as “treating” or “treatment” or “to treat” or “alleviating” or “to alleviate” refer to therapeutic measures that cure, slow down, lessen symptoms of, and / or halt progression of a diagnosed pathologic condition or disorder. Thus, those in need of treatment include those already diagnosed with the disorder, and may also include those who have minimal residual disease, or resistant disease, or replased disease. In certain embodiments, a subject is successfully “treated” for cancer according to the methods of the present invention if the patient shows one or more of the following: a reduction in the number of or complete absence of cancer cells; a reduction in the tumor size; inhibition of or an absence of cancer cell infiltration into peripheral organs including, for example, the spread of cancer into soft tissue and bone; inhibition of or an absence of tumor metastasis; inhibition or an absence of tumor growth; relief of one or more symptoms associated with the specific cancer; reduced morbidity and mortality; improvement in quality of life; reduction in tumorigenicity, tumorigenic frequency, or tumorigenic capacity, of a tumor; reduction in the number or frequency of cancer stem cells in a tumor; differentiation of tumorigenic cells to a non-tumorigenic state; increased progression-free survival (PFS), disease-free survival (DFS), or overall survival (OS), complete response (CR), partial response (PR), stable disease (SD), a decrease in progressive disease (PD), a reduced time to progression (TTP), or any combination thereof. Prophylactic or preventative measures refer to measures that prevent and / or slow the development of a targeted pathologic condition or disorder. Thus, those in need of prophylactic or preventative measures include those prone to have the disorder and those in whom the disorder is to be prevented. Prophylactic or preventative measures refer to therapeutic measures that prevent and / or slow the development of a targeted pathologic condition or disorder. Thus, those in need of prophylactic or preventative measures include those prone to have the disorder and those in whom the disorder is to be prevented. As used herein, the term “healthcare provider” refers to individuals or institutions which directly interact with and administer to living subjects, e.g., human patients. Non- limiting examples of healthcare providers include doctors, nurses, technicians, therapist, pharmacists, counselors, alternative medicine practitioners, medical facilities, doctor’s offices, hospitals, emergency rooms, clinics, urgent care centers, alternative medicine clinics / facilities, and any other entity providing general and / or specialized treatment, assessment, maintenance, therapy, medication, and / or advice relating to all, or any portion of, a patient’s state of health, including but not limited to general medical, specialized medical, surgical, and / or any other type of treatment, assessment, maintenance, therapy, medication and / or advice. In some aspects, a healthcare provider can administer or instruct another healthcare provider to administer a therapy to treat a cancer. “Administration” of a therapy, as used herein, includes prescribing a therapy to a subject as well as delivering, applying, or giving the therapy to a subject. A healthcare provider can implement or instruct another healthcare provider or patient to perform the following actions: obtain a sample, process a sample, submit a sample, receive a sample, transfer a sample, analyze or measure a sample, quantify a sample, provide the results obtained after analyzing / measuring / quantifying a sample, receive the results obtained after analyzing / measuring / quantifying a sample, compare / score the results obtained after analyzing / measuring / quantifying one or more samples, provide the comparison / score from one or more samples, obtain the comparison / score from one or more samples, administer a therapy or therapeutic agent (e.g., a CD123 / IL-3Ra binding agent), commence the administration of a therapy, cease the administration of a therapy, continue the administration of a therapy, temporarily interrupt the administration of a therapy, increase the amount of an administered therapeutic agent, decrease the amount of an administered therapeutic agent, continue the administration of an amount of a therapeutic agent, increase the frequency of administration of a therapeutic agent, decrease the frequency of administration of a therapeutic agent, maintain the same dosing frequency on a therapeutic agent, replace a therapy or therapeutic agent by at least another therapy or therapeutic agent, combine a therapy or therapeutic agent with at least another therapy or additional therapeutic agent. These actions can be performed by a healthcare provider automatically using a computer-implemented method (e.g., via a web service or stand-alone computer system). “Polynucleotide” or “nucleic acid,” as used interchangeably herein, refer to polymers of nucleotides of any length, and include DNA and RNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. A polynucleotide can comprise modified nucleotides, such as methylated nucleotides and their analogs. If present, modification to the nucleotide structure can be imparted before or after assembly of the polymer. The sequence of nucleotides can be interrupted by non-nucleotide components. A polynucleotide can be further modified after polymerization, such as by conjugation with a labeling component. Other types of modifications include, for example, “caps,” substitution of one or more of the naturally occurring nucleotides with an analog, internucleotide modifications such as, for example, those with uncharged linkages (e.g, methyl phosphonates, phosphotriesters, phosphoamidates, cabamates, etc.) and with charged linkages (e.g., phosphorothioates, phosphorodithioates, ezc.), those containing pendant moieties, such as, for example, proteins (e.g., nucleases, toxins, antibodies, signal peptides, ply-L-lysine, etc.), those with intercalators (e.g., acridine, psoralen, efc.), those containing chelators (e.g., metals, radioactive metals, boron, oxidative metals, etc.), those containing alkylators, those with modified linkages (e.g., alpha anomeric nucleic acids, ezc.), as well as unmodified forms of the polynucleotide(s). Further, any of the hydroxyl groups ordinarily present in the sugars can be replaced, for example, by phosphonate groups, phosphate groups, protected by standard protecting groups, or activated to prepare additional linkages to additional nucleotides, or can be conjugated to solid supports. The 5° and 3’ terminal OH can be phosphorylated or substituted with amines or organic capping group moieties of from 1 to 20 carbon atoms. Other hydroxyls can also be derivatized to standard protecting groups. Polynucleotides can also contain analogous forms of ribose or deoxyribose sugars that are generally known in the art, including, for example, 2’-0-methyl-, 2’-0-allyl, 2’-fluoro- or 2’- azido-ribose, carbocyclic sugar analogs, alpha-anomeric sugars, epimeric sugars such as arabinose, xyloses or lyxoses, pyranose sugars, furanose sugars, sedoheptuloses, acyclic analogs and abasic nucleoside analogs such as methyl riboside. One or more phosphodiester linkages can be replaced by alternative linking groups. These alternative linking groups include, but are not limited to, embodiments wherein phosphate is replaced by P(O)S (“thioate™), P(S)S (“dithioate”), (O)NR; (“amidate”), P(O)R, P(O)OR”", CO or CHz (“formacetal”), in which each R or R is independently H or substituted or unsubstituted alkyl (1-20 C) optionally containing an ether (-O-) linkage, aryl, alkenyl, cycloalkyl, cycloalkenyl or araldyl. Not all linkages in a polynucleotide need be identical. The preceding description applies to all polynucleotides referred to herein, including RNA and DNA. The term “vector” means a construct, which is capable of delivering, and expressing, one or more gene(s) or sequence(s) of interest in a host cell. Examples of vectors include, but are not limited to, viral vectors, naked DNA or RNA expression vectors, plasmid, cosmid or phage vectors, DNA or RNA expression vectors associated with cationic condensing agents, DNA or RNA expression vectors encapsulated in liposomes, and certain eukaryotic cells, such as producer cells. The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The polymer can be linear or branched, it can comprise modified amino acids, and it can be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified naturally or by intervention; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation or modification, such as conjugation with a labeling component. Also included within the definition are, for example, polypeptides containing one or more analogs of an amino acid (including, for example, unnatural amino acids, ezc.), as well as other modifications known in the art. It is understood that, because the polypeptides of this invention are based upon antibodies, in certain embodiments, the polypeptides can occur as single chains or associated chains. In some embodiments, a polypeptide, peptide, or protein is non-naturally occurring. In some embodiments, a polypeptide, peptide, or protein is purified from other naturally occurring components. In some embodiments, the polypeptide, peptide, or protein is recombinantly produced. The terms “identical” or percent “identity” in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software are known in the art that can be used to obtain alignments of amino acid or nucleotide sequences. One such non- limiting example of a sequence alignment algorithm is the algorithm described in Karlin et al., Proc. Natl. Acad. Sci. 87:2264-2268, 1990, as modified in Karlin et al., Proc. Natl. Acad. Sci. 90:5873-5877, 1993, and incorporated into the NBLAST and XBLAST programs (Altschul ez al., Nucleic Acids Res. 25:3389-3402, 1991). In certain embodiments, Gapped BLAST can be used as described in Altschul et al., Nucleic Acids Res. 25:3389-3402, 1997; BLAST-2, WU- BLAST-2 (Altschul et al., Methods in Enzymology 266:460-480, 1996), ALIGN, ALIGN-2 (Genentech, South San Francisco, California) or Megalign (DNASTAR) are additional publicly available software programs that can be used to align sequences. In certain embodiments, the percent identity between two nucleotide sequences is determined using the GAP program in GCG software (e.g., using a NWSgapdna. CMP matrix and a gap weight of 40, 50, 60, 70, or 90 and a length weight of 1, 2, 3, 4, 5, or 6). In certain alternative embodiments, the GAP program in the GCG software package, which incorporates the algorithm of Needleman and Wunsch (J. Mol. Biol. (48):444-453, 1970) can be used to determine the percent identity between two amino acid sequences (e.g., using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8,6, or4 and a length weight of 1, 2, 3, 4, 5). Alternatively, in certain embodiments, the percent identity between nucleotide or amino acid sequences is determined using the algorithm of Myers and Miller (CABIOS, 4: 11-17, 1989). For example, the percent identity can be determined using the ALIGN program (version 2.0) and using a PAM120 with residue table, a gap length penalty of 12 and a gap penalty of 4. Appropriate parameters for maximal alignment by particular alignment software can be determined by one skilled in the art. In certain embodiments, the default parameters of the alignment software are used. In certain embodiments, the percentage identity “X” of a first amino acid sequence to a second sequence amino acid is calculated as 100 x (Y / Z), where Y is the number of amino acid residues scored as identical matches in the alignment of the first and second sequences (as aligned by visual inspection or a particular sequence alignment program) and Z is the total number of residues in the second sequence. If the length of a first sequence is longer than the second sequence, the percent identity of the first sequence to the second sequence will be longer than the percent identity of the second sequence to the first sequence. As a non-limiting example, whether any particular polynucleotide has a certain percentage sequence identity (e.g., is at least 80% identical, at least 85% identical, at least 90% identical, and in some embodiments, at least 95%, 96%, 97%, 98%, or 99% identical) to a reference sequence can, in certain embodiments, be determined using the Bestfit program (Wisconsin Sequence Analysis Package, Version 8 for Unix, Genetics Computer Group, University Research Park, 575 Science Drive, Madison, WI 53711). Bestfit uses the local homology algorithm of Smith and Waterman, 4dvances in Applied Mathematics 2: 482-489, 1981, to find the best segment of homology between two sequences. When using Bestfit or any other sequence alignment program to determine whether a particular sequence is, for instance, 95% identical to a reference sequence according to the present invention, the parameters are set such that the percentage of identity is calculated over the full length of the reference nucleotide sequence and that gaps in homology of up to 5% of the total number of nucleotides in the reference sequence are allowed. In some embodiments, two nucleic acids or polypeptides of the invention are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. In certain embodiments, identity exists over a region of the sequences that is at least about 10, about 20, about 40-60 residues in length or any integral value therebetween, or over a longer region than 60-80 residues, at least about 90-100 residues, or the sequences are substantially identical over the full length of the sequences being compared, such as the coding region of a nucleotide sequence for example. A “conservative amino acid substitution” is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative substitution. In certain embodiments, conservative substitutions in the sequences of the polypeptides and antibodies of the invention do not abrogate the binding of the polypeptide or antibody containing the amino acid sequence, to the antigen(s), i.e., the CD123 / IL-3Ra to which the polypeptide or antibody binds. Methods of identifying nucleotide and amino acid conservative substitutions which do not eliminate antigen-binding are well-known in the art (see, e.g., Brummell er al., Biochem. 32:1180-1187, 1993; Kobayashi ez al., Protein Eng. 12(10):879-884, 1999; and Burks et al., Proc. Natl. Acad. Sci. USA 94:412-417, 1997). As used herein, “P-glycoprotein 1,” also known as “permeability glycoprotein,” “P-gp or Pgp,” “multidrug resistance protein 1 (MDR1),” “ATP-binding cassette sub-family B member 1 (ABCB1),” or “cluster of differentiation 243 (CD243),” is an ABC-transporter of the MDR / TAP subfamily that transports a wide variety of substrates across extra- and intracellular membranes. It is an ATP-dependent efflux pump with broad substrate specificity. P-gp is extensively distributed and expressed in the intestinal epithelium where it pumps xenobiotics (such as toxins or drugs) back into the intestinal lumen, in liver cells where it pumps them into bile ducts, in the cells of the proximal tubule of the kidney where it pumps them into urine-conducting ducts, and in the capillary endothelial cells composing the blood-brain barrier and blood-testis barrier, where it pumps them back into the capillaries. Some cancer cells also express large amounts of P-gp, which renders these cancers multi- drug resistant. “Alkyl” as used herein refers to a saturated linear or branched-chain monovalent hydrocarbon radical of one to twenty carbon atoms. Examples of alkyl include, but are not limited to, methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-methyl-1-propyl, -CH.CH(CH3),), 2- butyl, 2-methyl-2-propyl, 1-pentyl, 2-pentyl 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3- methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl), 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2- pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3- dimethyl-2-butyl, 1-heptyl, 1-octyl, and the like. Preferably, the alkyl has one to ten carbon atoms. More preferably, the alkyl has one to four carbon atoms. The number of carbon atoms in a group can be specified herein by the prefix “Cxx, wherein x and xx are integers. For example, “Ci4alkyl” is an alkyl group having from 1 to 4 carbon atoms. The term “compound” or “cytotoxic compound,” are used interchangeably. They are intended to include compounds for which a structure or formula or any derivative thereof has been disclosed in the present invention or a structure or formula or any derivative thereof that has been incorporated by reference. The term also includes, stereoisomers, geometric isomers, tautomers, solvates, metabolites, and salts (e.g., pharmaceutically acceptable salts) of a compound of all the formulae disclosed in the present invention. The term also includes any solvates, hydrates, and polymorphs of any of the foregoing. The specific recitation of “stereoisomers,” “geometric isomers,” “tautomers,” “solvates,” “metabolites,” “salt”, “conjugates,” “conjugates salt,” “solvate,” “hydrate,” or “polymorph” in certain aspects of the invention described in this application shall not be interpreted as an intended omission of these forms in other aspects of the invention where the term “compound” is used without recitation of these other forms. The term “chiral” refers to molecules that have the property of non-superimposability of the mirror image partner, while the term “achiral” refers to molecules that are superimposable on their mirror image partner. The term “stereoisomer” refers to compounds that have identical chemical constitution and connectivity, but different orientations of their atoms in space that cannot be interconverted by rotation about single bonds. “Diastereomer” refers to a stereoisomer with two or more centers of chirality and whose molecules are not mirror images of one another. Diastereomers have different physical properties, e.g. melting points, boiling points, spectral properties, and reactivities. Mixtures of diastereomers can separate under high resolution analytical procedures such as crystallization, electrophoresis and chromatography. “Enantiomers” refer to two stereoisomers of a compound that are non-supetimposable mirror images of one another. Stereochemical definitions and conventions used herein generally follow S. P. Parker, Ed., McGraw-Hill, Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, New York; and Eliel, E. and Wilen, S., Stereochemistry of Organic Compounds, John Wiley & Sons, Inc., New York, 1994. The compounds of the invention can contain asymmetric or chiral centers, and therefore exist in different stereoisomeric forms. It is intended that all stereoisomeric forms of the compounds of the invention, including but not limited to, diastereomers, enantiomers and atropisomers, as well as mixtures thereof such as racemic mixtures, form part of the present invention. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L, or R and S, are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and I or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these stereoisomers are identical except that they are mirror images of one another. A specific stereoisomer can also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric mixture. A 50:50 mixture of enantiomers is referred to as a racemic mixture or a racemate, which can occur where there has been no stereoselection or stereospecificity in a chemical reaction or process. The terms “racemic mixture” and “racemate” refer to an equimolar mixture of two enantiomeric species, devoid of optical activity. The term “tautomer” or “tautomeric form™ refers to structural isomers of different energies that are interconvertible via a low energy barrier. For example, proton tautomers (also known as prototropic tautomers) include interconversions via migration of a proton, such as keto-enol and imine-enamine isomerizations. Valence tautomers include interconversions by reorganization of some of the bonding electrons. The term “imine reactive reagent” refers to a reagent that is capable of reacting with an imine group. Examples of imine reactive reagent includes, but is not limited to, sulfites (H2S03, H2SO: or a salt of HSO3, SO3% or HSO; formed with a cation), metabisulfite (H2S:20s or a salt of S20s> formed with a cation), mono, di, tri, and tetra- thiophosphates (PO3SH3, PO2S2H3, POS3H3, PS4H; or a salt of PO3S¥, PO,S2*, POS:* or PSs? formed with a cation), thio phosphate esters ((RI0),PS(OR!), RiSH, RISOH, RiSO,H, RiSO3H), various amines (hydroxyl amine (e.g., NH,OH), hydrazine (e.g., NHoNH), NH0-Ri, R°NH-R}, NH:-Ri), NH2-CO-NH2, NH,-C(=S)-NH2 thiosulfate (H2S203 or a salt of $:03% formed with a cation), dithionite (H>S,04 or a salt of S:04> formed with a cation), phosphorodithioate (P(=S)(OR¥)(SH)(OH) or a salt thereof formed with a cation), hydroxamic acid (RXC(=0)NHOH or a salt formed with a cation), hydrazide (R“*CONHNH,), formaldehyde sulfoxylate (HOCH>SO:H or a salt of HOCH,SO> formed with a cation, such as HOCH2SO» Na"), glycated nucleotide (such as GDP-mannose), fludarabine or a mixture thereof, wherein R!and RY are each independently a linear or branched alkyl having 1 to 10 carbon atoms and are substituted with at least one substituent selected from -N(R),, -CO>H, -SOsH, and -POsH; Ri and RY can be further optionally substituted with a substituent for an alkyl described herein; RI is a linear or branched alkyl having 1 to 6 carbon atoms; and R¥ is a linear, branched or cyclic alkyl, alkenyl or alkynyl having 1 to 10 carbon atoms, aryl, heterocyclyl or heteroaryl (preferably, R¥ is a linear or branched alkyl having 1 to 4 carbon atoms; more preferably, R¥ is methyl, ethyl or propyl). Preferably, the cation is a monovalent cation, such as Na or K*. Preferably, the imine reactive reagent is selected from sulfites, hydroxyl amine, urea and hydrazine. More preferably, the imine reactive reagent is NaHSO3 or KHSOs. The phrase “pharmaceutically acceptable salt” as used herein, refers to pharmaceutically acceptable organic or inorganic salts of a compound of the invention. Exemplary salts include, but are not limited, to sulfate, citrate, acetate, oxalate, chloride, bromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucuronate, saccharate, formate, benzoate, glutamate, methanesulfonate “mesylate,” ethanesulfonate, benzenesulfonate, p-toluenesulfonate, pamoate (i.e., 1,1’-methylene-bis-(2-hydroxy-3-naphthoate)) salts, alkali metal (e.g., sodium and potassium) salts, alkaline earth metal (e.g., magnesium) salts, and ammonium salts. A pharmaceutically acceptable salt can involve the inclusion of another molecule such as an acetate ion, a succinate ion or other counter ion. The counter ion can be any organic or inorganic moiety that stabilizes the charge on the parent compound. Furthermore, a pharmaceutically acceptable salt can have more than one charged atom in its structure. Instances where multiple charged atoms are part of the pharmaceutically acceptable salt can have multiple counter ions. Hence, a pharmaceutically acceptable salt can have one or more charged atoms and / or one or more counter ion. If the compound of the invention is a base, the desired pharmaceutically acceptable salt can be prepared by any suitable method available in the art, for example, treatment of the free base with an inorganic acid, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, methanesulfonic acid, phosphoric acid and the like, or with an organic acid, such as acetic acid, maleic acid, succinic acid, mandelic acid, fumaric acid, malonic acid, pyruvic acid, oxalic acid, glycolic acid, salicylic acid, a pyranosidyl acid, such as glucuronic acid or galacturonic acid, an alpha hydroxy acid, such as citric acid or tartaric acid, an amino acid, such as aspartic acid or glutamic acid, an aromatic acid, such as benzoic acid or cinnamic acid, a sulfonic acid, such as p-toluenesulfonic acid or ethanesulfonic acid, or the like. If the compound of the invention is an acid, the desired pharmaceutically acceptable salt can be prepared by any suitable method, for example, treatment of the free acid with an inorganic or organic base, such as an amine (primary, secondary or tertiary), an alkali metal hydroxide or alkaline earth metal hydroxide, or the like. Illustrative examples of suitable salts include, but are not limited to, organic salts derived from amino acids, such as glycine and arginine, ammonia, primary, secondary, and tertiary amines, and cyclic amines, such as piperidine, morpholine and piperazine, and inorganic salts derived from sodium, calcium, potassium, magnesium, manganese, iron, copper, zinc, aluminum and lithium. As used herein, the term “solvate” means a compound that further includes a stoichiometric or non-stoichiometric amount of solvent such as water, isopropanol, acetone, ethanol, methanol, DMSO, ethyl acetate, acetic acid, and ethanolamine dichloromethane, 2- propanol, or the like, bound by non-covalent intermolecular forces. Solvates or hydrates of the compounds are readily prepared by addition of at least one molar equivalent of a hydroxylic solvent such as methanol, ethanol, 1-propanol, 2-propanol or water to the compound to result in solvation or hydration of the imine moiety. A “metabolite” or “catabolite” is a product produced through metabolism or catabolism in the body of a specified compound, a derivative thereof, or a conjugate thereof, or salt thereof. Metabolites of a compound, a derivative thereof, or a conjugate thereof, can be identified using routine techniques known in the art and their activities determined using tests such as those described herein. Such products can result for example from the oxidation, hydroxylation, reduction, hydrolysis, amidation, deamidation, esterification, deesterification, enzymatic cleavage, and the like, of the administered compound. Accordingly, the invention includes metabolites of compounds, a derivative thereof, or a conjugate thereof, of the invention, including compounds, a derivative thereof, or a conjugate thereof, produced by a process comprising contacting a compound, a derivative thereof, or a conjugate thereof, of this invention with a mammal for a period of time sufficient to yield a metabolic product thereof. The phrase “pharmaceutically acceptable” indicates that the substance or composition must be compatible chemically and / or toxicologically, with the other ingredients comprising a formulation, and / or the mammal being treated therewith. The term “protecting group” or “protecting moiety” refers to a substituent that is commonly employed to block or protect a particular functionality while reacting other functional groups on the compound, a derivative thereof, or a conjugate thereof. For example, an “amine-protecting group” or an “amino-protecting moiety” is a substituent attached to an amino group that blocks or protects the amino functionality in the compound. Such groups are well known in the art (see for example P. Wuts and T. Greene, 2007, Protective Groups in Organic Synthesis, Chapter 7, J. Wiley & Sons, NJ) and exemplified by carbamates such as methyl and ethyl carbamate, FMOC, substituted ethyl carbamates, carbamates cleaved by 1,6-B-elimination (also termed “self immolative™), ureas, amides, peptides, alkyl and aryl derivatives. Suitable amino-protecting groups include acetyl, trifluoroacetyl, t-butoxycarbonyl (BOC), benzyloxycarbonyl (CBZ) and 9- fluorenylmethylenoxycarbonyl (Fmoc). For a general description of protecting groups and their use, see P. G.M. Wuts & T. W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, New York, 2007. The term “amino acid” refers to naturally occurring amino acids or non-naturally occurring amino acid. In one embodiment, the amino acid is represented by NH,-C(R®'R*)- C(=0)OH, wherein R* and R*" are each independently H, an optionally substituted linear, branched or cyclic alkyl, alkenyl or alkynyl having 1 to 10 carbon atoms, aryl, heteroaryl or heterocyclyl or R* and the N-terminal nitrogen atom can together form a heteroycyclic ring (e.g., as in proline). The term “amino acid residue” refers to the corresponding residue when one hydrogen atom is removed from the amine and / or carboxy end of the amino acid, such as -NH-C(R*'R#)-C(=0)0-. The term “cation” refers to an ion with positive charge. The cation can be monovalent (e.g., Na*, K*, NHs" etc.), bi-valent (e.g., Ca?*, Mg?", etc.) or multi-valent (e.g., AP" etc.). Preferably, the cation is monovalent. The term “reactive ester group” refers to a group an ester group that can readily react with an amine group to form amide bond. Exemplary reactive ester groups include, but are not limited to, N-hydroxysuccinimide esters, N-hydroxyphthalimide esters, N-hydroxy sulfo- succinimide esters, para-nitrophenyl esters, dinitrophenyl esters, pentafluorophenyl esters and their derivatives, wherein said derivatives facilitate amide bond formation. In certain embodiments, the reactive ester group is a N-hydroxysuccinimide ester or a N-hydroxy sulfo- succinimide ester. The term “amine reactive group” refers to a group that can react with an amine group to form a covalent bond. Exemplary amine reactive groups include, but are not limited to, reactive ester groups, acyl halides, sulfonyl halide, imidoester, or a reactive thioester groups. In certain embodiments, the amine reactive group is a reactive ester group. In one embodiment, the amine reactive group is a N-hydroxysuccinimide ester or a N-hydroxy sulfo-succinimide ester. The term “thiol-reactive group” refers to a group that can react with a thiol (-SH) group to form a covalent bond. Exemplary thiol-reactive groups include, but are not limited to, maleimide, haloacetyl, aloacetamide, vinyl sulfone, vinyl sulfonamide or vinyal pyridine. In one embodiment, the thiol-reactive group is maleimide. As used in the present disclosure and claims, the singular forms “a,” “an,” and “the” include plural forms unless the context clearly dictates otherwise. It is understood that wherever embodiments are described herein with the language “comprising,” otherwise analogous embodiments described in terms of “consisting of” and / or “consisting essentially of’ are also provided. The term “and / or” as used in a phrase such as “A and / or B” herein is intended to include both “A and B,” “A or B,” “A,” and “B.” Likewise, the term “and / or” as used in a phrase such as “A, B, and / or C” is intended to encompass each of the following embodiments: A, B, and C; A, B,or C; Aor C; A or B; Bor C; A and C; A and B; B and C; A (alone); B (alone); and C (alone). Antibodies, Compounds, and Immunoconjugates Nomenclature As used herein, the nomenclature used for the anti-CD123 antibodies, cytotoxic compounds, and their immunoconjugates generally adopt the following meanings. CD123-3, -6, and -14 (or CD123 Mu-3, -6, and -14; or muCD123-3, -6, and 14) are three murine anti-CD123 monoclonal antibodies. The CDR1-3 sequences of the heavy and light chains (VH-CDR1-3, and VL-CDR1-3) are provided in Tables 1 and 2, with the associated SEQ ID NOs: 1-25. The heavy chain variable region (HCVR) sequences are provided in Table 3A with the associated SEQ ID NOs: 26, 28, and 30. Their light chain variable region (LCVR) sequences are provided in Table 4A with the associated SEQ ID NOs: 27, 29, and 31. The full length heavy chain (HC) sequences of the murine antibodies are provided in Table 5 (SEQ ID NOs: 42, 44, and 46), and the full length light chain (LC) sequences of the murine antibodies are provided in Table 6 (SEQ ID NOs: 43, 45, and 47). chCD123-3, -6, and -14 are the corresponding murine-human chimeric antibodies having the murine heavy and light chain variable regions and the human constant region sequences. For example, the chimeric antibody chCD123-6 is comprised of the mouse HCVR and LCVR of SEQ ID NOs: 28 and 29, respectively, together with the human IgG1 and Kappa constant sequences for the heavy and light chains, respectively. See Example 3. huCD123-3, -6, and -14 are the corresponding humanized antibodies. When the humanization is by way of CDR grafting of the 6 corresponding murine CDR regions (HC and LC CDR1-3), the letter “G” immediately follows the clone designation, which is in turn followed by a version number that designates the origin of the human light chain and heavy chain variable region sequences. Thus huCD123-6Gv4.6 refers to the humanized CD123 antibody based on grafting (“G”) the 6 CDR regions from the corresponding muCDR123-6 antibody, onto the human light chain variable region Gv4 and the heavy chain variable region Gv6. Similarly, -Gv4.7 comprises human light chain variable region Gv4 and heavy chain variable region Gv7; and -Gv1.1 comprises human light chain variable region Gv1 and heavy chain variable region Gvl1. The three HCVR sequences, huCD123-6Gv1, -Gv6, and -Gv7 are provided in Table 3A (SEQ ID NOs: 32 and 34, with SEQ ID NO: 34 representing both -Gv6 and -Gv7 since they differ only at the 2 residue Xaa), and their DNA coding sequences in Table 3B (SEQ ID NOs: 62, 64, and 66). The three full length HC sequences, huCD123-6Gv1, -Gv6, and - Gv7 are provided in Table 5 (SEQ ID NOs: 48 and 50, with SEQ ID NO: 50 representing both full length -Gv6 and -Gv7 since they differ only at the 2% residue Xaa). The two LCVR sequences, huCD123-6Gv1 and -Gv4, are provided in Table 4A (SEQ ID NOs: 33 and 35, and their DNA coding sequences in Table 4B (SEQ ID NOs: 63, and 65). The two full length LC sequences, huCD123-6Gv1 and -Gv4, are provided in Table 6 (SEQ ID NOs: 49 and 51). ‘When humanization is by way of resurfacing, the resurfaced heavy chain sequences are designated by “rh” immediately following the murine CD123 antibody clone number, and are further designated by one of two version of the resurfaced sequences, v1.0 or v1.1. Thus huCD123-6rhv1.0 and -rhv1.1 are resurfaced heavy chain sequences with CDR regions corresponding to the muCD123-6 antibody, with version designation of 1.0 and 1.1 respectively. See HCVR SEQ ID NOs: 39 and 40 in Table 3A, and SEQ ID NOs: 68 and 69 in Table 3B. Also see full length HC SEQ ID NOs: 59 and 60 in Table 5. Likewise, the only version of the resurfaced light chain sequence, huCD123-6rlv1.0, has LCVR SEQ ID NO: 41 in Table 4A, and full length LC SEQ ID NO: 61 in Table 6. A resurfaced antibody having huCD123-6rhv1.0 and huCD123-6rlv1.0 is huCD123- 6Rv1.0; and a resurfaced antibody having huCD123-6rhv1.1 and huCD123-6rlv1.0 is huCD123-6Rv1.1. NTS2 or “S2” for short refers to an antibody having an engineered Ser at the N- terminus of heavy chain. The S2 variant of the huCD123-6Gv6 / 7 has HCVR sequence SEQ ID NO: 38 in Table 3A, and full length HC protein sequence SEQ ID NO: 53 in Table 5. Likewise, NTS3 or “S3” for short refers to an antibody having an engineered Ser at the N-terminus of light chain. The S3 variant of the huCD123-6Gv4 has LCVR sequence SEQ ID NO: 37 in Table 4A, and full length LC protein sequence SEQ ID NO: 58 in Table 6. An antibody comprising an engineered N-terminal Ser (either S2 or S3) may be conjugated with a cytotoxic drug / agent through either the oxidized N-terminal Ser, or through the “conventional” Lys linkage. If the drug linkage is through oxidized N-terminal Ser, the conjugate name contains a “SeriMab” designation. If the drug linkage is through Lys, then the conjugate name does not contain SeriMab (despite the fact that there is an S2 or S3 designation to signal the presence of engineered Ser at the N-terminus). The particular linkage type will also be apparent based on the cytotoxin reactive group. For example, huCD123-6Gv4.7S3-SeriMab-D8 refers to conjugate between D8 and the humanized CD123 antibody huCD123-6Gv4.7S3, through the oxidized N-terminal Ser on the light chain. The humanized CD123 antibody has the grafted murine CD123-6 CDR regions, the human LC Gv4 and heavy chain Gv7, and the N-terminal of the light chain has an engineered Ser (S3). In contrast, huCD123-6Gv4.7S3-sSPDB-DI refers to conjugate between D1 and the same humanized CD123 antibody huCD123-6Gv4.7S3, through Lys linkage via a sulfonated SPDB linker. In certain embodiments, if both the light chain and heavy chain N-termini contain the engineered Ser, “S253” or “S2S3-SeriMab’ may appear in the antibody name. Certain antibodies of the invention have an engineered Cys in the heavy chain CH3 domain, at a position corresponding to the same Kabat position of the 5% to the last Cys in SEQ ID NO: 54. Such HCs or antibodies comprising such HCs contain the designation CysMab. Thus huCD123-6Gv4.6-CysMab is a humanized CD123 antibody that has grafted muCD123-6 CDR regions, is based on the human light chain Gv4 and heavy chain Gv6 sequences, wherein an engineered Cys is located in the HC CH3 region at a position corresponding to the 5% to the last Cys in SEQ ID NO: 54. Similarly, its heavy chain sequence is huCD123-6Gv6-CysMab. In addition, huCD123-6Gv4.6S2-CysMab is otherwise identical, but has an engineered Ser at the N-terminus of the heavy chain, and its heavy chain sequence is huCD123-6Gv6S2-CysMab. The resurfaced antibody described above may be further engineered to contain N- terminal Ser at either the light chain (S3 variant of the resurfaced antibody) or the heavy chain (S2 variant of the resurfaced antibody), or both (see below). Alternatively or in addition, the resurfaced antibody may have an engineered Cys in the heavy chain CH3 domain at a position corresponding to the same Kabat position of the 5* to the last Cys of SEQ ID NO: 54 (the CysMab version of the resurfaced antibody). A resurfaced antibody can have both engineered Cys and N-terminal Ser. In the conjugates formed between such CysMab and cytotoxin, however, at least in theory, the cytotoxin can be linked to the CysMab either through the Cys or through the conventional Lys. As used herein, however, without specific indication, a conjugate with a CysMab designation refers to a conjugate between a CysMab and a cytotoxin though the Cys- linkage (not the Lys linkage). The particular linkage type will also be apparent based on the cytotoxin reactive group. Other variations or combinations of the above general nomenclature are also contemplated and will be readily apparent to one of skill in the art. For example, huCD123- 6Rv1.1-CysMab is the resurfaced version of huCD123-6 (v1.1) that has an engineered Cys located in the HC CH3 region at a position corresponding to the 5% to the last Cys in SEQ ID NO: 54. The antibodies or antigen-binding fragments thereof of the invention may be conjugated to certain cytotoxic agents, either through linkage with the Lys side chain amino group, the Cys side chain thiol group, or an oxidized N-terminal Ser / Thr. Certain representative (non-limiting) cytotoxic agents described in the specification (including the examples) are listed below for illustration purpose. Note that most compounds such as DI, D2, D4, DGN462, D3, D6, etc., may be sulfonated (not shown here, but see FIG. 17 compound sD1, FIG. 15 compound sDGN462, and the FIG. 16 compound sD8) at one of the indolinobenzodiazepine monomers in certain examples. For compound D5’, both indolinobenzodiazepine monomers may be sulfonated. Compound No. Structure D1 Soon D2 0 H i 0 NA Aon OY fi N H [ =N. 0. FZ 0. N—, 0 o DGN462 0. 0, SH AINA ~NX LQ N =N, O. 0. N—, Com wo | o o D3 0 0. ONHS AON oN NYS 2 : H N. 0. 0. N—, Cann oe o o 0 Jo Lng s-Shploogrni HN y N o o Ne, Cn nC © c Tid R PN Roo ots, N- OMe MeO N, | 0 0 Apt Aon NA Ne, wo TY 9 N LO Ns, ° recon | 0 6 » oo" ° 7 N, o. o. Ns, | 0 0 0, 9 3 MeO gO pron Sm Sod © NTL H 0 H N OL N= ° Ta H My J 0 AOA ~INY . ~N 0 No ~ Cans N He GF XG D8 To BS H Ho: o. wp NH, o o i os at Ch nl | o ° D9 H MeO oN ANNAN Oy, o H 1 et N O DO Ns, N OMe nd |g" $ Note that several agents only differ slightly due to the different linkage chemistry required for linking the cytotoxin to different antibody side chains (i.e., Lys-linkage, Cys- linkage, oxidized N-terminal Ser linkage). Nevertheless, these related cytotoxins are given different “D” designations. See D1 and D4, as well as D2, D5, and D8. Conjugates of the subject antibodies and the cytotoxic agents generally follow the nomenclature of the antibodies and cytotoxic agents as described above. For example, huCD123-6Gv4.6-sulfo-SPDB-D1 is a conjugate of the huCD123- 6Gv4.6 antibody to compound D1 through a sulfonated SPDB linker, at one or more Lys residues of the antibody. huCD123-6-CX1-1-DM1 is a conjugate of the huCD123-6 antibody conjugated with the cytotoxic agent DM1 via a triglycyl linker named “CX1-1 linker,” at one or more of the Lys residues of the antibody. See Example 9e. One notable exception is the conjugate huCD123-6-SeriMab-sD1 shown in FIGs. 7B and 17, in which the short linker sequence between the huCD123-6-SeriMab and the sD1 cytotoxin is not explicitly recited in the conjugate name. Similarly, conjugate huCD123-6- SeriMab-sDGN462 in FIG. 15 is also an exception to the general rules above. 2 CD123-Binding Agents In a first aspect, the present invention provides agents that specifically bind CD123 / IL-3Ra, such as human CD123 / IL-3Ra. These agents are generally referred to herein as “CD123 / IL-3Ra-binding agents.” In certain embodiments, the CD123 / IL-3Ra-binding agents are antibodies or antigen-binding fragments thereof (or “antibodies” for simplicity), immunoconjugates thereof or polypeptides thereof. The amino acid and nucleotide sequences for human and other species of CD123 / IL- 3Ra are known in the art. For example, the human CD123 / IL-3Ra splicing variant 1 protein sequence as depicted in NCBI RefSeq NP_002174 is reproduced below: 1 MVLLWLTLLL IALPCLLQTK EDPNPPITNL RMKAKAQQLT WDLNRNVTDI ECVKDADYSM 61 PAVNNSYCQF GAISLCEVTN YTVRVANPPF STWILFPENS GKPWAGAENL TCWIHDVDFL 121 SCSWAVGPGA PADVQYDLYL NVANRRQQYE CLHYKTDAQG TRIGCRFDDI SRLSSGSQSS 181 HILVRGRSAA FGIPCTDKFV VFSQIEILTP PNMTAKCNKT HSFMHWKMRS HFNRKFRYEL 241 QIQKRMQPVI TEQVRDRTSF QLLNPGTYTV QIRARERVYE FLSAWSTPQR FECDQEEGAN 301 TRAWRTSLLI ALGTLLALVC VEFVICRRYLV MQRLFPRIPH MKDPIGDSFQ NDKLVVWEAG 361 KAGLEECLVT EVQVVQKT (SEQ ID NO: 36) The above sequence shows the CD123 / IL-3R alpha precursor chain protein, which is composed by 378 amino acids, containing the extracellular domain (residues 1-306, including an 18-residue N-terminal signal peptide), a 20 amino acid transmembrane domain, and a short cytoplasmic tail of 52 amino acids. The human CD123 / IL-3Ra splicing variant 1 nucleic acid sequence as depicted in NCBI RefSeq NM_002183 is reproduced below: 1 GTCAGGTTCA TGGTTACGAA GCTGCTGACC CCAGGATCCC AGCCCGTGGG AGAGAAGGGG 61 GTCTCTGACA GCCCCCACCC CTCCCCACTG CCAGATCCTT ATTGGGTCTG AGTTTCAGGG 121 GTCGGGECCCC AGCCTCGACET TATAAMAACAC CTCAATCGCGC GAGTACAACC TTCGOTTICT 181 CTTCGGGGAA AGCTGCTTTC AGCGCACACG GGAAGATATC AGAAACATCC TAGGATCAGG 241 ACACCCCAGA TCTTCTCAAC TGGAACCACG AAGGCTGTTT CTTCCACACA GTACTTTGAT 301 CTCCATTTAA GCAGGCACCT CTGTCCTGCG TTCCGGAGCT GCGTTCCCGA TGGTCCTCCT 361 TTGGCTCACG CTGCTCCTGA TCGCCCTGCC CTGTCTCCTG CAAACGAAGG AAGATCCARA 421 CCCACCAATC ACGAACCTAA GGATGAAAGC AAAGGCTCAG CAGTTGACCT GGGACCTTAA 481 CAGAAATGTG ACCGATATCG AGTGTGTTAA AGACGCCGAC TATTCTATGC CGGCAGTGAA 541 CAATAGCTAT TGCCAGTTTG GAGCAATTTC CTTATGTGAA GTGACCAACT ACACCGTCCG 601 AGTGGCCAAC CCACCATTCT CCACGTGGAT CCTCTTCCCT GAGAACAGTG GGAAGCCTTG 661 GGCAGGTGCG GAGAATCTGA CCTGCTGGAT TCATGACGTG GATTTCTTGA GCTGCAGCTG 121 GGCGGTAGGC CCGGGEGLCE CCGCGGACGT CCAGTACGAC CTGTACTTGA ACGTTGCCAA 781 CAGGCGTCAA CAGTACGAGT GTCTTCACTA CAAAACGGAT GCTCAGGGAA CACGTATCGG 841 GTGTCGTTTC GATGACATCT CTCGACTCTC CAGCGGTTCT CAAAGTTCCC ACATCCTGGT 901 GCGGGGCAGG AGCGCAGCCT TCGGTATCCC CTGCACAGAT AAGTTTGTCG TCTTTTCACA 961 GATTGAGATA TTAACTCCAC CCAACATGAC TGCAAAGTGT AATAAGACAC ATTCCTTTAT 1021 GCACTGGAAA ATGAGAAGTC ATTTCAATCG CAAATTTCGC TATGAGCTTC AGATACAAAA 1081 GAGAATGCAG CCTGTAATCA CAGAACAGGT CAGAGACAGA ACCTCCTTCC AGCTACTCARA 1141 TCCTGGAACG TACACAGTAC AAATAAGAGC CCGGGAAAGA GTGTATGAAT TCTTGAGCGC 1201 CTGGAGCACC CCCCAGCGCT TCGAGTGCGA CCAGGAGGAG GGCGCAAACA CACGTGCCTG 1261 GCGGACGTCG CTGCTGATCG CGCTGGGGAC GCTGCTGGCC CTGGTCTGTG TCTTCGTGAT 1321 CTGCAGAAGG TATCTGGTGA TGCAGAGACT CTTTCCCCGC ATCCCTCACA TGAAAGACCC 1381 CATCGGTGAC AGCTTCCAARA ACGACAAGCT GGTGGTCTGG GAGGCGGGCA AAGCCGGCCT 1441 GGAGGAGTGT CTGGTGACTG AAGTACAGGT CGTGCAGAAA ACTTGAGACT GGGGTTCAGG 1501 GCTTGTGGGG GTCTGCCTCA ATCTCCCTGG CCGGGCCAGG CGCCTGCACA GACTGGCTGC 1561 TGGACCTGCG CACGCAGCCC AGGAATGGAC ATTCCTAACG GGTGGTGGGC ATGGGAGATG 1621 CCTGTGTAAT TTCGTCCGAA GCTGCCAGGA AGAAGAACAG AACTTTGTGT GTTTATTTCA 1681 TGATAAAGTG ATTTTTTTTT TTTTAACCCA AAA (SEQ ID NO: 52) Proteins and nucleic acid sequences of CD123 / IL-3Ra from other non-human species can be readily retrieved from public database such as GenBank, using sequence search tools known in the art (such as NCBI BLASTp or BLASTn) and the above protein and nucleic acid sequences as query sequences, respectively. Such sequences from the non-human species can be aligned with the human sequences using any of many art-recognized sequence alignment tools, such as those described herein and above, such that any amino acid residues or nucleotides “corresponding to” any given human sequences or regions of sequences can be readily obtained. Thus, one aspect of the invention provides an antibody or antigen-binding fragment thereof that: (a) binds an epitope within amino acids 101 to 346 of human CD123 antigen, and (b) inhibits IL3-dependent proliferation in antigen-positive TF-1 cells. In some embodiments, an anti-CD123 / IL-3Ra antibody or antigen-binding fragment thereof can specifically binds to an epitope of SEQ ID NO: 36. In certain embodiments, the epitope is within a region corresponding to residues 101-346 of human CD123 / IL-3Ra. In certain embodiments, the epitope is within a region corresponding to residues 101-204 of SEQ ID NO: 36. In certain other embodiments, the epitope is within a region corresponding to residues 205-346 of SEQ ID NO: 36. In certain embodiments, the epitope is not within a region corresponding to residues 1-100 of human CD123 / IL-3Ra. In certain embodiments, the CD123 / IL-3Ra-binding agents (e.g., antibodies) inhibit IL3-dependent signaling, such as IL-3-dependent proliferation of CD123-positive TF-1 cells. While not wishing to be bound by any particular theory, the CD123 / IL-3Ra-binding agents (e.g., antibodies) of the invention bind to CD123, such as within a CD123 region corresponding to residues 101-346 (e.g., residues 101-204, or 205-346) of human CD123 / IL- 3Ra, and prevents, reduces, diminishes, or otherwise inhibits productive binding between CD123 and the IL-3 ligand, and / or productive binding between CD123 and the common beta chain CD131, leading to reduced or abolished IL-3 dependent signaling. In a related aspect, the invention provides an antibody or antigen-binding fragment thereof that: (a) binds an epitope within amino acids 1 to 100 of human CD123 antigen, and (b) inhibits IL3-dependent proliferation in antigen-positive TF-1 cells, with an ICsp value of 0.1 nM or less (e.g., 0.08 nM, 0.05 nM, 0.03 nM). In certain embodiments, binding by the CD123 / IL-3Ra-binding agents (e.g., antibodies) of the invention inhibits (e.g., preferentially inhibits) the proliferation of leukemic stem cells (LSCs), leukemia progenitors (LPs), or leukemic blasts, but do not substantially inhibit the proliferation of the normal hematopoietic stem cells (HSCs). Inhibition of cell proliferation can be conducted using any standard assays known in the art, including but are not limited to flow cytometry. For example, normal HSCs, LSCs, LPs, and leukemia blasts can be separated using flow cytometry based on the difference on expression of cell surface markers, and the relative number of the surviving or remaining cells, after incubating with the testing agents, can be quantitatively measured and compared. Inhibition of cell proliferation of the LSCs, LPs, or leukemia blasts as compared to normal HSCs can also be assayed using in vitro potency assay on primary cancer cells, such as primary AML cells. For example, AML cells (or normal human bone marrow samples containing normal HSCs) can be exposed to various concentrations of the subject anti-CD123 antibodies, antigen-binding fragments thereof, immuno-conjugates thereof, or polypeptide comprising the antibodies or antigen-binding fragments for 24 hrs. Non-targeting (isotype- matched) antibodies, or immuno-conjugates (ADC) control can also be used in the assay. Samples can be divided into a short-term liquid culture (STLC) assay to measure the cytotoxicity toward the LSCs, LPs, or leukemia blasts; and a long-term liquid culture (LTLC) assay to measure the effect on the LSCs and normal HSCs. STLC can be used to measure colony forming units 10-14 days in cells, e.g., following plating in semi-solid MethoCult H4230 medium (Stemcell technologies). The LTLC assays can be performed similarly with the addition of growth factors for long-term culture 5-7 weeks. In both assays, colonies can be counted to determine colony forming units per number of cells initially plated. LTLC colonies can be further analyzed for the presence of cancer (e.g., AML) molecular markers using PCR or FISH or both. In certain embodiments, the antibody or antigen-binding fragment thereof binds to human CD123 antigen-positive cells with a dissociation constant (Ka) of 0.3 nM or lower. In certain embodiments, the antibodies or antigen-binding fragments thereof bind to human CD123 with a Ky between 0.05 and 0.3 nM, or between 0.05 and 0.2 nM, or between 0.05 and 0.1 nM, or between 0.01 nM and 0.3 nM, or between 0.01 nM and 0.2 nM, or between 0.01 nM and 0.1 nM. In certain embodiments, the antibodies or antigen-binding fragments thereof bind to cynomolgus monkey CD123. In certain embodiments, the antibodies or antigen-binding fragments thereof bind to cynomolgus monkey CD123 with a Kq between 0.05 and 0.3 nM, or between 0.05 and 0.2 nM, or between 0.05 and 0.1 nM. In certain embodiments, the antibodies or antigen-binding fragments thereof bind both human and cynomolgus monkey CD123 with a substantially similar binding affinity. In certain embodiments, the antibodies or antigen-binding fragments thereof bind to both human and cynomolgus monkey CD123 with Ka between 0.05 and 0.3 nM, or between 0.05 and 0.2 nM, or between 0.05 and 0.1 nM. In certain embodiments, the K value is based on cell-based binding assay. In certain embodiments, the Kq value is measured by flow cytometry. In certain embodiments, the Ka value is measured by surface plasmon resonance (such as by using the BIOCORE™ surface plasmon resonance system). In certain embodiments, the Ks value is measured by radioimmunoassay (RIA). In certain embodiments, the Ka is measured by any other art- recognized methods. In certain embodiments, the antibody or antigen-binding fragment thereof inhibits at least 50% of IL3-dependent proliferation in antigen-positive TF-1 cells at a concentration of 0.5 nM or lower. In certain embodiments, the CD123 / IL-3Ra-binding agents are CD123 / IL-3Ra antibodies or antigen-binding fragments thereof that comprise a heavy chain variable region (HCVR) and a light chain variable region (LCVR), each comprising three CDR regions (e.g., CDR1-CDR3 for the HCVR, and CDR1-CDR3 for the LCVR), wherein the composite CDRs for the HCVR and LCVR are any of the sequences provided in Tables 1 and 2 below. Table 1 Heavy Chain Variable Region CDR Amino Acid Sequences VH-CDR3 EGENGYYDAMDY (SEQ ID NO:4) Alt Name VH-CDR2 CDI233 | CDI23Mu-3 |SYVMH | YIKPYKDGTK (SEQID | (SEQIDNO:2) NO:1) EGGNDYYDTMDY (SEQ ID NO:11) YIKPYKDGTKYNEKFKG (Kabat) (SEQ ID NO:3) CD123-6 CDI123Mu-6 SSIMH YIKPYNDGTK (SEQID | Murine + Grafted NO:5) (SEQ ID NO:6) YIRPYNDGTR (resurfaced version 1.0) (SEQ ID NO:7) YIKPYNDGTKYNEKFKG (Kabat Murine + Grafted) (SEQ ID NO:8) YIRPYNDGTRYNQKFQG (Kabat - resurfaced v1.0) (SEQ ID NO:9) YIKPYNDGTKYNQKFQG (Kabat - resurfaced v1.1) (SEQ ID NO:10) CDI123-14 | CDI23Mu-14 | NYAMS TINSGGSFTY (SEQ ID (SEQ IDNO:13) NO:12) QSEAYYGYDKRT (SEQ ID NO: 15) QSEAYYGYDKRTW FAY (SEQ ID NO:70) TINSGGSFTY YPDSVKG (Kabat) (SEQ ID NO:14) Table 2 Light Chain Variable Region CDR Amino Acid Sequences Alt Name VL-CDRI VL-CDR2 VL-CDR3 CDI123-3 | CDI23Mu-3 | KASQDINKYIA | YTSTLQP LQYDNLLYT (SEQIDNO:17) | (SEQ ID NO:18) CDI123-6 | CD123Mu-6 KASQDINSYLS | RVNRLVD LQYDAFPYT (SEQIDNO:221) | (SEQ ID NO:22) RASQDINSYLS | RVNRLVS Humanized (SEQ ID NO:71) (SEQ ID NO:20) RASQDINSYLA | (SEQ ID NO:72) CDI123-14 | CD123Mu-14 | RASQSVGTSIH | YASESIS QQSKSWPLT (SEQIDNO:23) | (SEQIDNO:24) | (SEQ ID NO:25) In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprise: a) at least one heavy chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR1 is selected from the group consisting of: SEQ ID NOs: 1, 5, and 12, CDR2 is selected from the group consisting of: SEQ ID NOs: 2-3, 6-10, and 13-14, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 4, 11, 15 and 70; and b) at least one light chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR1 is selected from the group consisting of: SEQ ID NOs: 16, 19-20, 23 and 72, CDR2 is selected from the group consisting of: SEQ ID NOs: 17, 21, 24 and 71, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 18, 22, and 25. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprise: a) at least one heavy chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR1 is selected from the group consisting of: SEQ ID NOs: 1, 5, and 12, CDR? is selected from the group consisting of: SEQ ID NOs: 2-3, 6-10, and 13-14, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 4, 11, and 15; and b) at least one light chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR1 is selected from the group consisting of: SEQ ID NOs: 16, 19-20, and 23, CDR? is selected from the group consisting of: SEQ ID NOs: 17, 21, and 24, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 18, 22, and 25. In certain embodiments, the conservative amino acid substitutions comprise a substitution of a Lys in a CDR by an Arg (such as the Lys-to-Arg substitutions in SEQ ID NOs: 6 and 7, 8 and 9, and 19 and 20). In certain embodiments, the antibody is a CDR- grafted humanized antibody comprising mouse CDR regions, and wherein one or more (e.g., 1,2,3,4,5,6,7, or 8) heavy chain and / or light chain framework region vernier zone residues of the antibody is of mouse origin. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprise: a) an immunoglobulin heavy chain variable region comprising a CDRI1 having an amino acid sequence set forth in SEQ ID NO: 1, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 2 or 3, and, optionally, a CDR3 having an amino acid sequence set forth in SEQ ID NO: 4; and 2) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 16, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 17, and, optionally, a CDR3 having an amino acid sequence set forth in SEQ ID NO: 18. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 2. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 3. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprise: a) an immunoglobulin heavy chain variable region comprising a CDRI having an amino acid sequence set forth in SEQ ID NO: 5, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 6, 7, 8, 9, or 10, and, optionally, a CDR3 having an amino acid sequence set forth in SEQ ID NO: 11; and 2) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 19 or 20, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 21, and, optionally, a CDR3 having an amino acid sequence set forth in SEQ ID NO: 22. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 6, and CDR1 of the light chain variable region is SEQ ID NO: 19. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 7, and CDR1 of the light chain variable region is SEQ ID NO: 19. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 8, and CDR of the light chain variable region is SEQ ID NO: 19. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 9, and CDR1 of the light chain variable region is SEQ ID NO: 19. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 10, and CDR1 of the light chain variable region is SEQ ID NO: 19. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 6, and CDR of the light chain variable region is SEQ ID NO: 20. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 7, and CDR1 of the light chain variable region is SEQ ID NO: 20. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 8, and CDR1 of the light chain variable region is SEQ ID NO: 20. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 9, and CDR of the light chain variable region is SEQ ID NO: 20. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 10, and CDR1 of the light chain variable region is SEQ ID NO: 20. For each pairwise combinations of heavy chain variable region CDR2 with light chain variable region CDR1 above, the heavy chain variable region CDR1 and 3 are SEQ ID NOs: 5 and 11, respectively, and the light chain variable region CDR2 and 3 are SEQ ID NOs: 21 and 22, respectively. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprise: a) an immunoglobulin heavy chain variable region comprising a CDRI having an amino acid sequence set forth in SEQ ID NO: 12, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 13 or 14, and, optionally, a CDR3 having an amino acid sequence set forth in SEQ ID NO: 15; and 2) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 23, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 24, and, optionally, a CDR3 having an amino acid sequence set forth in SEQ ID NO: 25. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 13. In certain embodiments, CDR2 of the heavy chain variable region is SEQ ID NO: 14. In certain embodiments, CDR1 sequences from the light chain and heavy chain of one antibody (such as SEQ ID NOs: 5 and 19) can be combined with CDR2 sequences from the light chain and heavy chain of another antibody (such as SEQ ID NOs: 2 and 17), and optionally can be combined with CDR3 sequences from the light chain and heavy chain of the same (e.g., SEQ ID NOs: 4 and 18, or 11 and 22) or yet another antibody (e.g., SEQ ID NOs: 15 and 25). All possible combinations based on SEQ ID NOs: 1-25 in Table 1, particularly those pertaining to the same antibody number (e.g., all six light chain and heavy chain CDRs come from CD123-3, or from CD123-6, or from CD123-14) are contemplated herein without exhaustively enumerating all the specific combinations. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof have conserved amino acid substitutions over 1, 2, or 3 consecutive residues in any one or more CDR sequences above. That is, in some embodiments, the subject antibodies and antigen-binding fragments thereof may have conserved amino acid substitutions over 1, 2, or 3 consecutive residues, in any one or more of SEQ ID NOs: 1-25. In certain embodiments, the CD123 / IL-3Ra-binding agents are CD123 / IL-3Ra antibodies or antigen-binding fragments thereof that comprise a heavy chain variable region (HCVR) and a light chain variable region (LCVR), wherein the HCVR and LCVR are any of the sequences provided in Tables 3A and 4A below. Selected corresponding nucleic acid sequences encoding the HCVR and LCVR are in Tables 3B and 4B. Table 3A Heavy Chain Variable Region Amino Acid Sequences Antibody Alt Name VH Amino Acid Sequence (SEQ ID NO) CD123-14 huCD123-6Gv1 VYMELSSLRSEDTAVYYCAREGGNDYYDTMDYWGQGTL | VTVSS (SEQ ID NO:32) huCD123-6Gv6 / 7 QXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQA huCD123-6 Gv6 / 7-NTS2 huCD123-6rhv1.0 huCD123-6rhvl.1 “CDI1233 CDI23Mu-3 | EFQLQQSGPEVVKPGASVKMSCKASGY TFTSYVMHWMEKQ KPGQGLEWIGYIKPYKDGTKYNEKFKGKATLISDKPSSTAY MELSSLTSEDSAVYYCAREGENGYYDAMDYWGQGTSVIV SS (SEQ ID NO:26) "CDI123-6 CDI23Mu-6 | EFQLQQSGPELVKPGASVKMSCKASGYIFTSSIMHWMKQK PGQGLEWIGYIKPYNDGTK YNEKFKGKATLTSDKSSSTAN MELNSLTSEDSAVYYCAREGGNDYYDTMDYWGQGTSVT VSS (SEQ ID NO:28) “CD123-14 CDI23Mu-14 | EVKLVESGGDLVKPGGSLKLSCAASGFTESNYAMSWVRQ NSEKRLEWVATINSGGSFTYYPDSVKGRFTISRDNAKDSLY LQMSSLNSEDTAMYYCARQSEAYYGYDKRTWFAYWGQG TLVTVSS (SEQ ID NO:30) “huCD123-6Gvl QVQLVQSGAEVKKPGASVKVSCKASGYGFTSSIMHWVRQ APGQGLEWMGYIKPYNDGTKYNEKFKGRVTMTRDTSTST VYMELSSLRSEDTAVYYCAREGGNDYYDTMDYWGQGTL | VTVSS (SEQ ID NO:32) TWCDIZEGVET | QXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQA PGQGLEWIGYIKPYNDGTK YNEKFKGRATLTSDRSTSTAY MELSSLRSEDTAVYYCAREGGNDYYDTMDYWGQGTLVT | VSS (SEQ ID NO:34) “huCDI236 SXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQA Gv6 / 7-NTS2 PGQGLEWIGYIKPYNDGTKYNEKFKGRATLTSDRSTSTAY MELSSLRSEDTAVYYCAREGGNDYYDTMDYWGQGTLVT | VSS (SEQ ID NO:38) TCDIEEII0 | QVQLVQSGAEVVKPGASVKMSCKASGYTFTSSIMHWMKQ KPGQGLEWIGYIRPYNDGTRYNQKFQGKATLTSDRSSSTA NMELNSLTSEDSAVYYCAREGGNDYYDTMDYWGQGTSV | TVSS (SEQ ID NO:39) CDE] QFQLVQSGAEVVKPGASVKMSCKASGYTFTSSIMHWMKQ KPGQGLEWIGYIKPYNDGTKYNQKFQGKATLTSDKSSSTA NMELNSLTSEDSAVYYCAREGGNDYYDTMDYWGQGTSV TVSS (SEQ ID NO:40) * In all sequences above in which the 2° residue from the N-terminus is X (or Xaa), e.g., SEQ ID NOs: 34 and 38, X is F for Gv6 sequences, while X is V for Gv7 sequences. Table 3B Selected Heavy Chain Variable Region Nucleic Acid Sequences Antibody VH DNA Sequence (SEQ ID NO) huCD123-6 VuGvl huCDI123-6 VuGvé huCDI123-6 VuGv7 huCD123-6 Vyrhvl1.0 huCDI123-6 Vurhvl.1 AAGCTTGCCACCATGGGCTGGTCTTGTATTATTCTGTTTCT GGTGGCCACCGCAACAGGCGTTCACAGTCAATTCCAGCTG GTCCAGTCCGGCGCCGAGGTTGTCAAACCTGGTGCCAGCG TAAAGATGTCTTGCAAAGCTAGCGGCTATACTTTCACTTCT TCAATTATGCACTGGATGAAGCAAAAGCCTGGACAGGGCC TGGAATGGATCGGCTACATTAAACCTTATAACGACGGCAC AAAGTACAATCAGAAGTTCCAAGGAAAGGCAACCCTGACC TCAGACAAGTCTTCATCCACTGCCAACATGGAACTTAATAG TCTTACCTCTGAGGATTCCGCTGTCTATTATTGCGCTCGGG AGGGGGGGAACGACTATTACGACACCATGGACTACTGGGG ACAGGGCACCAGTGTTACCGTGTCCAGCGCTAGCACCAAG GGCCC (SEQ ID NO:69) * The bolded bases mark the first codon of the mature variable region amino acid sequence Table 4A Light Chain Variable Region Amino Acid Sequences Antibody Alt Name VL Amino Acid Sequence (SEQ ID NO) [coizs1e huCD123-6Gv1 huCD123-6Gv4 huCD123-6Gv4- | NTS3 huCDI123-6rlv1.0 [opis DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPG KGPRLLIHYTSTLQPGIPSRFSGSGSGRDYSFSISNLEPEDIAT YYCLQYDNLLYTFGGGTKLELKR(SEQ ID NO:27) [opis DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPG KSPKTLIYRVNRLVDGVPSRFSGSGSGQDYSLTISSLEYED MGIY YCLQYDAFPYTFGGGTKLEIKR(SEQ ID NO:29) [ooisia DILLTQSPAILSVSPGTRVSFSCRASQSVGTSIHWYQQRPNG FPRLLIKYASESISGIPSRFSGSGSGTDFTLNINSVESEDIADY YCQQSKSWPLTFGAGTKLELKR(SEQ ID NO:31) [ uCDIZ36GVT DIQMTQSPSSLSASVGDRVTITCRASQDINSYLAWFQQKPG KAPKSLIYRVNRLVSGVPSRFSGSGSGTDFTLTISSLQPEDF ATYYCLQYDAFPYTFGQGTKVEIKR (SEQ ID NO:33) [ uCDI236Gva DIQMTQSPSSLSASVGDRVTITCRASQDINSYLSWFQQKPG KAPKTLIYRVNRLVDGVPSRFSGSGSGNDY TLTISSLQPEDF ATYYCLQYDAFPYTFGQGTKVEIKR (SEQ ID NO:35) huCDIZ3-6Gva- | SIQMTQSPSSLSASVGDRVTITCRASQDINSYLSWEFQQKPG NTS3 KAPKTLIYRVNRLVDGVPSRFSGSGSGNDYTLTISSLQPEDF | ATYYCLQYDAFPYTFGQGTKVEIKR (SEQ ID NO:37) [WCDI | DIQMTQSPSSMSASVGERVTITCRASQDINSYLSWFQQKPG KSPKTLIYRVNRLVDGVPSRFSGSGSGQDYSLTISSLEPEDM GIYYCLQYDAFPYTFGQGTKLEIKR (SEQ ID NO:41) Table 4B Selected Light Chain Variable Region Nucleic Acid Sequences huCDI123-6 ViGv4 huCDI123-6VL (resurfaced) Antibod Alt Name VL DNA Sequence (SEQ ID NO) huCD123-6 GAATTCGCCACCATGGGTTGGTCTTGTATAATCCTGTTCC ViGvl TGGTCGCTACCGCAACAGGGGTTCACTCAGACATCCAGA TGACCCAGAGTCCCTCTTCTCTGAGCGCTTCTGTTGGGG ACCGGGTGACCATCACCTGTCGGGCATCCCAGGACATCA ATTCTTACCTGGCTTGGTTCCAGCAGAAGCCCGGAAAAG CCCCTAAATCTCTCATTTACCGGGTAAACCGTTTGGTCTC CGGAGTGCCTTCAAGGTTTAGTGGATCTGGATCAGGTAC AGACTTCACTCTCACCATAAGCAGCCTGCAACCAGAGGA TTTCGCAACTTACTACTGCTTGCAGTATGACGCCTTCCCT TACACTTTCGGGCAGGGGACCAAAGTGGAAATAAAGCG TACG (SEQ ID NO:63) huCD123-6 GAATTCGCCACCATGGGTTGGTCCTGTATCATCCTCTTTC ViGv4 TGGTGGCAACTGCAACCGGCGTCCATAGCGACATTCAG ATGACACAGTCTCCTTCTTCCCTGAGCGCCAGCGTCGGG GACCGCGTGACTATCACATGTCGGGCCTCCCAGGACATT AACTCTTACCTCTCCTGGTTCCAGCAGAAGCCTGGGAAA GCCCCAAAGACACTGATATACAGGGTAAATCGTTTGGTT GACGGTGTACCATCACGATTTTCCGGTAGTGGGTCTGGA AACGATTACACTCTCACAATTAGCAGCCTGCAACCAGAG GACTTTGCAACATACTATTGCCTGCAGTACGATGCTTTTC CTTATACCTTCGGTCAGGGTACCAAGGTGGAAATTAAAC GTACG (SEQ ID NO:65 huCD123-6V,. GAATTCGCCACCATGGGCTGGTCATGTATTATCCTGTTTC (resurfaced) TGGTTGCAACCGCAACAGGAGTACACTCTGATATCCAGA TGACTCAGTCTCCCTCTTCTATGTCTGCTTCTGTGGGAGA GAGAGTCACCATCACCTGTCGCGCTTCCCAAGATATTAA TAGCTATCTGTCTTGGTTCCAACAGAAACCTGGCAAATC ACCCAAGACTCTGATTTATCGGGTTAACCGCCTGGTGGA CGGTGTGCCTTCACGCTTCTCCGGCAGCGGTAGTGGACA AGACTATAGCCTGACAATTTCTTCTCTTGAACCCGAGGA CATGGGAATCTACTATTGCTTGCAGTATGACGCTTTTCCT TATACATTCGGCCAGGGCACAAAGCTGGAAATCAAACG TACG (SEQ ID NO:67) * The bolded bases mark the first codon of the mature variable region amino acid sequence. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: (a) a Vu sequence at least 95% identical to a reference Vu sequence selected from a group having amino acid sequences represented by SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38); and / or (b) a Vi sequence at least 95% identical to a reference Vi sequence selected from the group having amino acid sequences represented by SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37). In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: (a) a Vu sequence at least 96% identical to a reference Vu sequence selected from a group having amino acid sequences represented by SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38); and / or (b) a V1 sequence at least 96% identical to a reference Vi sequence selected from the group having amino acid sequences represented by SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37). In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: (a) a Vu sequence at least 97% identical to a reference Va sequence selected from a group having amino acid sequences represented by SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38); and / or (b) a Vi sequence at least 97% identical to a reference Vi sequence selected from the group having amino acid sequences represented by SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37). In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: (a) a Vu sequence at least 98% identical to a reference Vu sequence selected from a group having amino acid sequences represented by SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38); and / or (b) a Vi sequence at least 98% identical to a reference Vi sequence selected from the group having amino acid sequences represented by SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37). In certain embodiments, the anti-CD123 antibodies and antigen-binding fragments thereof comprises: (a) a Vu sequence at least 99% identical to a reference Vu sequence selected from a group having amino acid sequences represented by SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38); and / or (b) a V1 sequence at least 99% identical to a reference Vi sequence selected from the group having amino acid sequences represented by SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37). In certain embodiments, the CD123 / IL-3Ra antibody / antigen-binding fragment thereof having a certain percentage of sequence identity to SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably SEQ ID NOs: 26, 28, 30, 32, 34, and 38) and / or 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37) differs from SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38) and / or 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37) by conservative amino acid substitutions only, such as 1, 2, or 3 conservative amino acid substitutions. In certain embodiments, the conservative amino acid substitutions are substitutions of 1, 2, or 3 consecutive amino acids in one or more CDR regions of the heavy and / or light chains. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: (a) a Vu sequence identical to a reference Vu sequence selected from a group having amino acid sequences represented by SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (or SEQ ID NOs: 26, 28, 30, 32, 34, and 38); and / or (b) a V1 sequence identical to a reference V1 sequence selected from the group having amino acid sequences represented by SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (or SEQ ID NOs: 27, 29, 31, 35, and 37). In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a Vu sequence as set forth in SEQ ID NO: 26, and / or a VL sequence as set forth in SEQ ID NO: 27. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a Vu sequence as set forth in SEQ ID NO: 28, and / or a Vo sequence as set forth in SEQ ID NO: 29. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a Vu sequence as set forth in SEQ ID NO: 30, and / or a VL sequence as set forth in SEQ ID NO: 31. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a Vu sequence as set forth in SEQ ID NO: 34, and / or a VL sequence as set forth in SEQ ID NO: 35. In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises a Vu sequence and a Vi sequence with a combination of SEQ ID NOs. selected from the group consisting of: 32 / 33, 34 / 33, 38 / 33, 39 / 33, 40 / 33, 32 / 35, 34 / 35, 38 / 35, 39 / 35, 40 / 35, 32 / 37, 34 / 37, 38 / 37, 39 / 37, 40 / 37, 39 / 33, 39 / 35, 39 / 37, 39 / 41, 40 / 33, 40 / 35, 40 / 37, and 40 / 41. For example, in one embodiment, the anti-CD123 / IL-3Ra antibodies and antigen- binding fragments thereof comprises: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In certain embodiments, the Vu sequence is set forth in SEQ ID NO: 39, and the V1 sequence is set forth in SEQ ID NO: 41. In certain embodiments, the Vu sequence is set forth in SEQ ID NO: 40, and the V1. sequence is set forth in SEQ ID NO: 41. In a related embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 34; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa in SEQ ID NO: 34 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 34 is Val (V). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40, except that the first residue is replaced by Ser (S); and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41, except that the first residue is replaced by Ser (S). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the N-terminal residue is Ser, and except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41, except that the N-terminal residue is Ser. In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 38; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa in SEQ ID NO: 38 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 38 is Val (V). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 34; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, Xaa in SEQ ID NO: 34 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 34 is Val (V). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 56; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa in SEQ ID NO: 56 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 56 is Val ). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, Xaa in SEQ ID NO: 54 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 54 is Val VV). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41. In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa in SEQ ID NO: 54 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 54 is Val ). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 56; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 35. In certain embodiments, Xaa in SEQ ID NO: 56 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 56 is Val ). In another embodiment, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof comprises: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and, b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, Xaa in SEQ ID NO: 54 is Phe (F). In certain embodiments, Xaa in SEQ ID NO: 54 is Val VV). In certain embodiments, the anti-CD123 / IL-3Ra antibodies and antigen-binding fragments thereof specifically binds CD123 / IL-3Ro. In certain embodiments, the CD123 / IL- 3Ra antibody or antigen-binding fragment thereof is a murine, chimeric, humanized, or human antibody or antigen-binding fragment thereof that specifically binds CD123 / IL-3Ra. In certain embodiments, the humanized antibody or antigen-binding fragment thereof is a CDR-grafted or resurfaced antibody or antigen-binding fragment thereof. In certain embodiments, the anti-CD123 / IL-3Ra antibodies are full-length antibodies. The full-length antibodies may comprise any of the antibodies above defined by the 1-4 CDR (e.g., CDR1 and CDR2 of the heavy chain; CDR1 and CDR2 of the heavy and light chains), 1-6 CDR sequences (e.g., CDR1-CDR3 of the heavy chain; CDR1-CDR3 of the heavy and light chains), or any of the antibodies above defined by the LCVR and / or the HCVR, or any of the full-length antibodies having a heavy chain sequence in Table 5, or any of the full- length antibodies having a light chain sequence in Table 6, or any of the full-length antibodies having a heavy chain sequence in Table 5 and a light chain sequence in Table 6. Table 5 Full-Length Heavy Chain Amino Acid Sequences Antibody Full-Length Heavy Chain Amino Acid Sequence (SEQ ID NO) CDI123-3 | EFQLQQSGPEVVKPGASVKMSCKASGYTFTSY VMHWMKQKPGQGLEWIGY IKPYKDGTKYNEKFKGKATLISDKPSSTAYMELSSLTSEDSAVYYCAREGEN GYYDAMDYWGQGTSVTVSSAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKG YFPEPVTVTWNSGSLSSGVHTFPAVLESDLYTLSSSVTVPSSPRPSETVTCNVA HPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCV VVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWL NGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVY TIPPPKEQMAKDKVSLTC MITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSNWE AGNTFTCSVLHEGLHNHHTEKSLSHSPGK (SEQ ID NO:42) CD123-6 EFQLQQSGPELVKPGASVKMSCKASGYIFTSSIMHWMKQKPGQGLEWIGYIK PYNDGTKYNEKFKGKATLTSDKSSSTANMELNSLTSEDSAVYYCAREGGND 6 NTS2 (or S27) 6 CysMab YYDTMDYWGQGTSVTVSSAKTTPPSVYPLAPGSAAQTNSMVTLGCLVKGYF PEPVTVTWNSGSLSSGVHTFPAVLESDLYTLSSSVTVPSSMRPSETVTCNVAH PASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVTCVV VDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQDWLN GKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSLTCM ITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSNWEA GNTFTCSVLHEGLHNHHTEKSLSHSPGK (SEQ ID NO:44) CD123-14 | EVKLVESGGDLVKPGGSLKLSCAASGFTFSNYAMSWVRQNSEKRLEWVATI NSGGSFTYYPDSVKGRFTISRDNAKDSLYLQMSSLNSEDTAMYYCARQSEAY YGYDKRTWFAYWGQGTLVTVSSAKTTPPSVYPLAPGSAAQTNSMVTLGCLV KGYFPEPVTVTWNSGSLSSGVHTFPAVLESDLYTLSSSVTVPSSPRPSETVTCN VAHPASSTKVDKKIVPRDCGCKPCICTVPEVSSVFIFPPKPKDVLTITLTPKVT CVVVDISKDDPEVQFSWFVDDVEVHTAQTQPREEQFNSTFRSVSELPIMHQD ‘WLNGKEFKCRVNSAAFPAPIEKTISKTKGRPKAPQVYTIPPPKEQMAKDKVSL TCMITDFFPEDITVEWQWNGQPAENYKNTQPIMNTNGSYFVYSKLNVQKSN WEAGNTFTCSVLHEGLHNHHTEKSLSHSPGK (SEQ ID NO:46) huCDI123- | QVQLVQSGAEVKKPGASVKVSCKASGYGFTSSIMHWVRQAPGQGLEWMGY 6Gv1 IKPYNDGTKYNEKFKGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCAREGG NDYYDTMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICN VNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMIS RTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRD ELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSK LTVDKSRWQQGNVFSCSVMHEALHNHY TQKSLSLSPG (SEQ ID NO:48) huCDI123- | QXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQAPGQGLEWIGYIK 6Gv6 / 7 PYNDGTKYNEKFKGRATLTSDRSTSTAYMELSSLRSEDTAVYYCAREGGND YYDTMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:50) huCDI123- | SXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQAPGQGLEWIGYIK 6 Gv6 / 7- | PYNDGTKYNEKFKGRATLTSDRSTSTAYMELSSLRSEDTAVYYCAREGGND NTS2 YYDTMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP (or “82”) | EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:53 huCDI123- | QXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQAPGQGLEWIGYIK 6 Gv6 / 7- | PYNDGTKYNEKFKGRATLTSDRSTSTAYMELSSLRSEDTAVYYCAREGGND CysMab YYDTMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLCLSPG (SEQ ID NO:54) huCDI123- | SXQLVQSGAEVKKPGASVKVSCKASGYIFTSSIMHWVRQAPGQGLEWIGYIK 6 Gv6 / 7S2- | PYNDGTKYNEKFKGRATLTSDRSTSTAYMELSSLRSEDTAVYYCAREGGND CysMab YYDTMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFP EPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNH KPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTV LHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTK NQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTV DKSRWQQGNVFSCSVMHEALHNHYTQKSLCLSPG (SEQ ID NO:56) huCDI23- | QVQLVQSGAEVVKPGASVKMSCKASGYTFTSSIMHWMKQKPGQGLEWIGYI 6rhv1.0 RPYNDGTRYNQKFQGKATLTSDRSSSTANMELNSLTSEDSAVYYCAREGGN DYYDTMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:59) huCDI23- | QFQLVQSGAEVVKPGASVKMSCKASGYTFTSSIMHWMKQKPGQGLEWIGYT 6rhvl.1 KPYNDGTKYNQKFQGKATLTSDKSSSTANMELNSLTSEDSAVYYCAREGGN DYYDTMDYWGQGTSVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDY FPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNV NHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISR TPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSV LTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG (SEQ ID NO:60) * In all sequences above in which the 2° residue from the N-terminus is X (or Xaa), e.g., SEQ ID NOs: 50, 53, 54, and 56, X is F for Gv6 sequences, while X is V for Gv7 sequences. In some embodiments, the Met (bolded) in SEQ ID NO:44 is Pro. Table 6 Full-Length Light Chain Amino Acid Sequences Antibod: Full-length Light Chain Amino Acid Sequence (SEQ ID NO) CDI123-3 | DIQMTQSPSSLSASLGGKVTITCKASQDINKYIAWYQHKPGKGPRLLIHYTS TLQPGIPSRFSGSGSGRDY SFSISNLEPEDIATYYCLQYDNLLYTFGGGTKLE LKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQN GVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKS FNRNEC (SEQ ID NO:43 CDI123-6 | DIKMTQSPSSMYASLGERVTITCKASQDINSYLSWFQQKPGKSPKTLIYRVN RLVDGVPSRFSGSGSGQDYSLTISSLEYEDMGIYYCLQYDAFPYTFGGGTK LEIKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSER QNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSY TCEATHKTSTSPIV KSFNRNEC (SEQ ID NO:45) CDI123-14 | DILLTQSPAILSVSPGTRVSFSCRASQSVGTSIHWYQQRPNGFPRLLIKYASE SISGIPSRFSGSGSGTDFTLNINSVESEDIADY YCQQSKSWPLTFGAGTKLEL KRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQN GVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKS FNRNEC (SEQ ID NO:47, huCDI123- | DIQMTQSPSSLSASVGDRVTITCRASQDINSYLAWFQQKPGKAPKSLIYRVN 6Gvl RLVSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCLQYDAFPYTFGQGTKV EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC (SEQ ID NO:49 huCDI123- | DIQMTQSPSSLSASVGDRVTITCRASQDINSYLSWFQQKPGKAPKTLIYRVN 6Gv4 RLVDGVPSRFSGSGSGNDYTLTISSLQPEDFATYYCLQYDAFPYTFGQGTK VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFNRGEC (SEQ ID NO:51 huCDI123- | SIQMTQSPSSLSASVGDRVTITCRASQDINSYLSWFQQKPGKAPKTLIYRVN 6Gv4- RLVDGVPSRFSGSGSGNDYTLTISSLQPEDFATYYCLQYDAFPYTFGQGTK NTS3 (or | VEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNAL “83”) QSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPV TKSFENRGEC (SEQ ID NO:58 huCDI23- | DIQMTQSPSSMSASVGERVTITCRASQDINSYLSWFQQKPGKSPKTLIYRVN 6riv1.0 RLVDGVPSRFSGSGSGQDYSLTISSLEPEDMGIYYCLQYDAFPYTFGQGTKL EIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQ SGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC (SEQ ID NO:61) In certain embodiments, the anti-CD123 / IL-3Ra antibodies are full-length antibodies comprising: (a) a heavy chain having at least about 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to any of the full-length heavy chain sequences above, such as any of the full-length heavy chain sequences in Table 5; and / or (b) a light chain having at least about 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to any of the full-length light chain sequences above, such as any of the full-length light chain sequences in Table 6. In certain embodiments, the anti-CD123 / IL-3Ra antibodies are full-length antibodies comprising a full length heavy chain sequence and a full-length light chain sequence combination selected from the group consisting of SEQ ID NOs: 42 / 43, 44 / 45, 46 / 47, 48 / 49, 50 / 49, 53 / 49, 54 / 49, 56 / 49, 59 / 49, 60 / 49, 48 / 51, 50 / 51, 53 / 51, 54 / 51, 56 / 51, 59 / 51, 60 / 51, 48 / 58, 50 / 58, 53 / 58, 54 / 58, 56 / 58, 59 / 58, 60 / 58, 59 / 49, 59 / 51, 59 / 58, 59 / 61, 60 / 49, 60 / 51, 60 / 58, and 60 / 61, or antibodies with at least about 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to any of the full-length heavy chain sequences and / or light chain sequences thereof. In certain embodiments, the anti-CD123 / IL-3Ra antibodies are full-length antibodies comprising a full-length heavy chain sequence and a full-length light chain sequence combination selected from the group consisting of SEQ ID NOs: 59 / 61, and 60 / 61, or antibodies with at least about 90%, 95%, 96%, 97%, 98%, or 99% sequence identity to any of the full-length heavy chain sequences and / or light chain sequences thereof. Such antibodies may further comprise engineered N-terminal Ser / Thr in the light chain, heavy chain, or both. Such antibodies may further comprise engineered Cys in the heavy chain CH3 domain in a position corresponding to the 5% to the last Cys of SEQ ID NO: 54. In certain embodiments, the anti-CD123 / IL-3Ra antibody is a murine, chimeric, humanized, or human antibody that specifically binds CD123 / IL-3Ra. In certain embodiments, the anti-CD123 / IL-3Ra antibody having a certain percentage of sequence identity to any of the full-length SEQ ID NOs differs from such SEQ ID NOs by conservative amino acid substitutions only, e.g., by 1, 2, 3, 4, or 5 consecutive conservative amino acid substitutions only. In certain embodiments, the conservative amino acid substitutions are outside the CDRs. In certain embodiments, the antigen-binding fragment thereof is or comprises a Fab, Fd, Fab’, F(ab’), single chain Fv or scFv, disulfide linked Fv, V-NAR domain, IgNar, intrabody, IgGACH2, minibody, F(ab’), tetrabody, triabody, diabody, single-domain antibody, DVD-Ig, Fcab, mAb2, (scFv),, or scFv-Fc, of any one of the above antibodies. In a related aspect, the invention also provides a polypeptide comprising any of the antibodies or antigen-binding fragments thereof, any of the Vi and / or VL sequences above, any of the HCVR and / or LCVR above, or any of the CDR sequence(s) of the HCVR and / or LCVR above. The polypeptide maybe, for example, a fusion with a non-antibody protein or domain. In certain embodiments, the fusion protein is not a fusion with a pseudomonas toxin. The affinity or avidity of an antibody for an antigen can be determined experimentally using any suitable method well known in the art, e.g., flow cytometry, enzyme-linked immunoabsorbent assay (ELISA), or radioimmunoassay (RIA), or kinetics (e.g., BIACORE™ analysis). Direct binding assays as well as competitive binding assay formats can be readily employed. See, for example, Berzofsky er al., “Antibody-Antigen Interactions,” in Fundamental Immunology, Paul, W. E., Ed., Raven Press: New York, N.Y. (1984); Kuby, Janis Immunology, W. H. Freeman and Company: New York, N.Y. (1992); and methods described herein. The measured affinity of a particular antibody-antigen interaction can vary if measured under different conditions (e.g., salt concentration, pH, temperature). Thus, measurements of affinity and other antigen-binding parameters (e.g., Kp or Ka, kon, kop) are made with standardized solutions of antibody and antigen, and a standardized buffer, as known in the art and such as the buffer described herein. In one aspect, binding assays can be performed using flow cytometry on cells expressing the CD123 / IL-3Ra antigen on the surface. For example, CD123 / IL-3Ra-positive cells can be incubated with varying concentrations of anti-CD123 / IL-3Ra antibodies using 1 x 10° cells per sample in 100 uL FACS buffer (e.g., RPMI-1640 medium supplemented with 2% normal goat serum). Then, the cells can be pelleted, washed, and incubated for 1 hr with 100 pL of FITC-conjugated goat-anti-mouse or goat-anti-human IgG-antibody (such as is obtainable from, for example Jackson Laboratory, 6 pg / mL in FACS buffer). The cells are then pelleted again, washed with FACS buffer and resuspended in 200 pL of PBS containing 1% formaldehyde. Samples can be acquired, for example, using a FACSCalibur flow cytometer with the HTS multiwell sampler and analyzed using CellQuest Pro (all from BD Biosciences, San Diego, US). For each sample the mean fluorescence intensity for FL1 (MFI) can be exported and plotted against the antibody concentration in a semi-log plot to generate a binding curve. A sigmoidal dose-response curve is fitted for binding curves and ECs values are calculated using programs such as GraphPad Prism v4 with default parameters (GraphPad software, San Diego, CA). ECso values can be used as a measure for the apparent dissociation constant “Ks” or “Kp” for each antibody. Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein (1975) Nature 256:495. Using the hybridoma method, a mouse, hamster, or other appropriate host animal, is immunized to elicit the production by lymphocytes of antibodies that will specifically bind to an immunizing antigen. Lymphocytes can also be immunized in vitro. Following immunization, the lymphocytes are isolated and fused with a suitable myeloma cell line using, for example, polyethylene glycol, to form hybridoma cells that can then be selected away from unfused lymphocytes and myeloma cells. Hybridomas that produce monoclonal antibodies directed specifically against a chosen antigen as determined by immunoprecipitation, immunoblotting, or by an in vitro binding assay (e.g., radioimmunoassay (RIA); enzyme-linked immunosorbent assay (ELISA)) can then be propagated either in vitro culture using standard methods (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, 1986) or in vivo as ascites tumors in an animal. The monoclonal antibodies can then be purified from the culture medium or ascites fluid as described for polyclonal antibodies. Alternatively monoclonal antibodies can also be made using recombinant DNA methods as described in U.S. Patent 4,816,567. The polynucleotides encoding a monoclonal antibody are isolated from mature B-cells or hybridoma cells, such as by RT- PCR using oligonucleotide primers that specifically amplify the genes encoding the heavy and light chains of the antibody, and their sequence is determined using conventional procedures. The isolated polynucleotides encoding the heavy and light chains are then cloned into suitable expression vectors, which when transfected into host cells such as E. coli cells, simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, monoclonal antibodies are generated by the host cells. Also, recombinant monoclonal antibodies or fragments thereof of the desired species can be isolated from phage display libraries expressing CDRs of the desired species as described (McCafferty et al., Nature 348:552-554, 1990; Clackson et al., Nature, 352:624-628, 1991; and Marks et al., J. Mol. Biol. 222:581-597, 1991). The polynucleotide(s) encoding a monoclonal antibody can further be modified in a number of different manners using recombinant DNA technology to generate alternative antibodies. In some embodiments, the constant domains of the light and heavy chains of, for example, a mouse monoclonal antibody can be substituted 1) for those regions of, for example, a human antibody to generate a chimeric antibody, or, 2) for a non- immunoglobulin polypeptide to generate a fusion antibody. In some embodiments, the constant regions are truncated or removed to generate the desired antibody fragment of a monoclonal antibody. Site-directed or high-density mutagenesis of the variable region can be used to optimize specificity, affinity, etc. of a monoclonal antibody. In some embodiments, the monoclonal antibody against the human CD123 / IL-3Ra is a humanized antibody. In certain embodiments, such antibodies are used therapeutically to reduce antigenicity and HAMA (human anti-mouse antibody) responses when administered to a human subject. Methods for engineering, humanizing or resurfacing non-human or human antibodies can also be used and are well known in the art. A humanized, resurfaced or similarly engineered antibody can have one or more amino acid residues from a source that is non- human, e.g., but not limited to, mouse, rat, rabbit, non-human primate or other mammal. These non-human amino acid residues are replaced by residues that are often referred to as “import” residues, which are typically taken from an “import” variable, constant or other domain of a known human sequence. Such imported sequences can be used to reduce immunogenicity or reduce, enhance or modify binding, affinity, on-rate, off-rate, avidity, specificity, half-life, or any other suitable characteristic, as known in the art. In general, the CDR residues are directly and most substantially involved in influencing CD123 / IL-3Ra binding. Accordingly, part or all of the non-human or human CDR sequences are maintained while the non-human sequences of the variable and constant regions can be replaced with human or other amino acids. Antibodies can also optionally be humanized, resurfaced, engineered or human antibodies engineered with retention of high affinity for the antigen CD123 / IL-3Ra and other favorable biological properties. To achieve this goal, humanized (or human) or engineered anti-CD123 / IL-3Ra antibodies and resurfaced antibodies can be optionally prepared by a process of analysis of the parental sequences and various conceptual humanized and engineered products using three-dimensional models of the parental, engineered, and humanized sequences. Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, i.e., the analysis of residues that influence the ability of the candidate immunoglobulin to bind its antigen, such as CD123 / IL-3Ro. In this way, framework (FR) residues can be selected and combined from the consensus and import sequences so that the desired antibody characteristic, such as increased affinity for the target antigen(s), is achieved. Humanization, resurfacing or engineering of antibodies of the present invention can be performed using any known method, such as but not limited to those described in, Winter (Jones et al., Nature 321:522, 1986; Riechmann er al., Nature 332:323, 1988; Verhoeyen et al., Science 239:1534, 1988, Sims et al., J. Immunol. 151:2296, 1993; Chothia and Lesk, J. Mol. Biol. 196:901, 1987, Carter et al., Proc. Natl. Acad. Sci. U.S.A. 89:4285, 1992; Presta et al., J. Immunol. 151:2623, 1993; Raguska et al., Proc. Natl. Acad. Sci. U.S.A. 91(3):969-973, 1994; U.S. Pat. Nos. 5,639,641, 5,723,323; 5,976,862; 5,824,514; 5,817,483; 5,814,476; 5,763,192; 5,723,323; 5,766,886; 5,714,352; 6,204,023; 6,180,370; 5,693,762; 5,530,101; 5,585,089; 5,225,539; 4,816,567; PCT / : US98 / 16280; US96 / 18978; US91 / 09630; US91 / 05939; US94 / 01234; GB89 / 01334; GB91 / 01134; GB92 / 01755; WO90 / 14443; 'W090 / 14424; W090 / 14430; EP 229246; 7,557,189; 7,538,195; and 7,342,110, each of which is entirely incorporated herein by reference, including the references cited therein. In certain alternative embodiments, the antibody to CD123 / IL-3Ra is a human antibody. Human antibodies can be directly prepared using various techniques known in the art. Immortalized human B lymphocytes immunized in vitro or isolated from an immunized individual that produce an antibody directed against a target antigen can be generated (See, e.g., Cole et al, Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boemer et al., 1991, J. Immunol, 147 (1):86-95; and U.S. Patent 5,750,373). Also, the human antibody can be selected from a phage library, where that phage library expresses human antibodies, as described, for example, in Vaughan ez al., Nat. Biotech. 14:309- 314, 1996, Sheets et al., Proc. Nat'l. Acad. Sci. 95:6157-6162, 1998, Hoogenboom and Winter, J. Mol. Biol. 227:381, 1991, and Marks et al., J. Mol. Biol. 222:581, 1991). Techniques for the generation and use of antibody phage libraries are also described in U.S. Patent Nos. 5,969,108, 6,172,197, 5,885,793, 6,521,404; 6,544,731; 6,555,313; 6,582,915; 6,593,081; 6,300,064; 6,653,068; 6,706,484; and 7,264,963; and Rothe et al., J. Mol. Bio. doi: 10.1016 / j,jmb.2007.12.018, 2007 (each of which is incorporated by reference in its entirety). Affinity maturation strategies and chain shuffling strategies (Marks ez al., Bio / Technology 10:779-783, 1992, incorporated by reference in its entirety) are known in the art and can be employed to generate high affinity human antibodies. Humanized antibodies can also be made in transgenic mice containing human immunoglobulin loci that are capable upon immunization of producing the full repertoire of human antibodies in the absence of endogenous immunoglobulin production. This approach is described in U.S. Patents 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; and 5,661,016. In certain embodiments are provided an antibody fragment to, for example, increase tumor penetration. Various techniques are known for the production of antibody fragments. Traditionally, these fragments are derived via proteolytic digestion of intact antibodies (for example Morimoto et al., Journal of Biochemical and Biophysical Methods 24: 107-117, 1993; Brennan ef al., Science 229:81, 1985). In certain embodiments, antibody fragments are produced recombinantly. Fab, Fv, and scFv antibody fragments can all be expressed in and secreted from E. coli or other host cells, thus allowing the production of large amounts of these fragments. Such antibody fragments can also be isolated from antibody phage libraries. The antibody fragment can also be linear antibodies as described in U.S. Patent 5,641,870, for example, and can be monospecific or bispecific. Other techniques for the production of antibody fragments will be apparent to the skilled practitioner. For the purposes of the present invention, it should be appreciated that modified antibodies can comprise any type of variable region that provides for the association of the antibody with the polypeptides of a human CD123 / IL-3Ra. In this regard, the variable region can comprise or be derived from any type of mammal that can be induced to mount a humoral response and generate immunoglobulins against the desired tumor associated antigen. As such, the variable region of the modified antibodies can be, for example, of human, murine, non-human primate (e.g., cynomolgus monkeys, macaques, etc.) or lupine origin. In some embodiments both the variable and constant regions of the modified immunoglobulins are human. In other embodiments the variable regions of compatible antibodies (usually derived from a non-human source) can be engineered or specifically tailored to improve the binding properties or reduce the immunogenicity of the molecule. In this respect, variable regions useful in the present invention can be humanized or otherwise altered through the inclusion of imported amino acid sequences. In certain embodiments, the variable domains in both the heavy and light chains are altered by at least partial replacement of one or more CDRs and, if necessary, by partial framework region replacement and sequence changing. Although the CDRs can be derived from an antibody of the same class or even subclass as the antibody from which the framework regions are derived, it is envisaged that the CDRs will be derived from an antibody of different class and in certain embodiments from an antibody from a different species. It may not be necessary to replace all of the CDRs with the complete CDRs from the donor variable region to transfer the antigen-binding capacity of one variable domain to another. Rather, it may only be necessary to transfer those residues that are necessary to maintain the activity of the antigen-binding site. Given the explanations set forth in U.S. Pat. Nos. 5,585,089, 5,693,761 and 5,693,762, it will be well within the competence of those skilled in the art, either by carrying out routine experimentation or by trial and error testing to obtain a functional antibody with reduced immunogenicity. Alterations to the variable region notwithstanding, those skilled in the art will appreciate that the modified antibodies of this invention will comprise antibodies (e.g., full- length antibodies or immunoreactive fragments thereof) in which at least a fraction of one or more of the constant region domains has been deleted or otherwise altered so as to provide desired biochemical characteristics such as increased tumor localization or reduced serum half-life when compared with an antibody of approximately the same immunogenicity comprising a native or unaltered constant region. In some embodiments, the constant region of the modified antibodies will comprise a human constant region. Modifications to the constant region compatible with this invention comprise additions, deletions or substitutions of one or more amino acids in one or more domains. That is, the modified antibodies disclosed herein can comprise alterations or modifications to one or more of the three heavy chain constant domains (CH1, CH2, or CH3) and / or to the light chain constant domain (CL). In some embodiments, modified constant regions wherein one or more domains are partially or entirely deleted are contemplated. In some embodiments, the modified antibodies will comprise domain deleted constructs or variants wherein the entire CH2 domain has been removed (ACH2 constructs). In some embodiments, the omitted constant region domain will be replaced by a short amino acid spacer (e.g., 10 residues) that provides some of the molecular flexibility typically imparted by the absent constant region. It will be noted that in certain embodiments, the modified antibodies can be engineered to fuse the CH3 domain directly to the hinge region of the respective modified antibodies. In other constructs it may be desirable to provide a peptide spacer between the hinge region and the modified CH2 and / or CH3 domains. For example, compatible constructs could be expressed wherein the CH2 domain has been deleted and the remaining CH3 domain (modified or unmodified) is joined to the hinge region with a 5-20 amino acid spacer. Such a spacer can be added, for instance, to ensure that the regulatory elements of the constant domain remain free and accessible or that the hinge region remains flexible. However, it should be noted that amino acid spacers can, in some cases, prove to be immunogenic and elicit an unwanted immune response against the construct. Accordingly, in certain embodiments, any spacer added to the construct will be relatively non-immunogenic, or even omitted altogether, so as to maintain the desired biochemical qualities of the modified antibodies. Besides the deletion of whole constant region domains, it will be appreciated that the antibodies of the present invention can be provided by the partial deletion or substitution of a few or even a single amino acid. For example, the mutation of a single amino acid in selected areas of the CH2 domain may be enough to substantially reduce Fc binding and thereby increase tumor localization. Similarly, it may be desirable to simply delete that part of one or more constant region domains that control the effector function (e.g., complement C1Q binding) to be modulated. Such partial deletions of the constant regions can improve selected characteristics of the antibody (serum half-life) while leaving other desirable functions associated with the subject constant region domain intact. Moreover, as alluded to above, the constant regions of the disclosed antibodies can be modified, e.g., through the mutation or substitution of one or more amino acids, which may enhance the profile of the resulting construct. In this respect it may be possible to disrupt the activity provided by a conserved binding site (e.g., Fc binding) while substantially maintaining the configuration and immunogenic profile of the modified antibody. Certain embodiments can comprise the addition of one or more amino acids to the constant region to enhance desirable characteristics such as decreasing or increasing effector function or provide for more cytotoxin or carbohydrate attachment. In such embodiments it can be desirable to insert or replicate specific sequences derived from selected constant region domains. The present invention further embraces variants and equivalents which are substantially homologous to the chimeric, humanized and human antibodies, or antibody fragments thereof, set forth herein. These can contain, for example, conservative substitution mutations, i.e., the substitution of one or more amino acids by similar amino acids. For example, conservative substitution refers to the substitution of an amino acid with another within the same general class such as, for example, one acidic amino acid with another acidic amino acid, one basic amino acid with another basic amino acid or one neutral amino acid by another neutral amino acid. What is intended by a conservative amino acid substitution is well known in the art, such as those defined hereinabove. The polypeptides of the present invention can be recombinant polypeptides, natural polypeptides, or synthetic polypeptides comprising an antibody, or fragment thereof, against a human CD123 / IL-3Ra. It will be recognized in the art that some amino acid sequences of the invention can be varied without significant effect of the structure or function of the protein. Thus, the invention further includes variations of the polypeptides which show substantial activity or which include regions of an antibody, or fragment thereof, against a CD123 antigen, such as a human CD123. Such mutants include deletions, insertions, inversions, repeats, and type substitutions. The polypeptides and analogs can be further modified to contain additional chemical moieties not normally part of the protein. Those derivatized moieties may improve the solubility, the biological half life or absorption of the protein. The moieties can also reduce or eliminate any desirable side effects of the proteins and the like. An overview for those moieties can be found in REMINGTON’S PHARMACEUTICAL SCIENCES, 20th ed., Mack Publishing Co., Easton, PA (2000). The isolated polypeptides described herein can be produced by any suitable method known in the art. Such methods range from direct protein synthetic methods to constructing a DNA sequence encoding isolated polypeptide sequences and expressing those sequences in a suitable transformed host. In some embodiments, a DNA sequence is constructed using recombinant technology by isolating or synthesizing a DNA sequence encoding a wild-type protein of interest. Optionally, the sequence can be mutagenized by site-specific mutagenesis to provide functional analogs thereof. See, e.g., Zoeller et al., Proc. Nat'l. Acad. Sci. USA 81:5662-5066, 1984, and U.S. Pat. No. 4,588,585. In some embodiments a DNA sequence encoding a polypeptide of interest (e.g., antibody, antigen-binding fragment, or polypeptide of the invention) would be completely or partially constructed by chemical synthesis using an oligonucleotide synthesizer. Such oligonucleotides can be designed based on the amino acid sequence of the desired polypeptide and selecting those codons that are favored in the host cell in which the recombinant polypeptide of interest will be produced. Standard methods can be applied to synthesize an isolated polynucleotide sequence encoding an isolated polypeptide of interest. For example, a complete amino acid sequence can be used to construct a back-translated gene. Further, a DNA oligomer containing a nucleotide sequence coding for the particular isolated polypeptide can be synthesized. For example, several small oligonucleotides coding for portions of the desired polypeptide can be synthesized and then ligated. The individual oligonucleotides typically contain 5° or 3° overhangs for complementary assembly. Once assembled (by synthesis, site-directed mutagenesis or another method), the polynucleotide sequences encoding a particular isolated polypeptide of interest will be inserted into an expression vector and operatively linked to an expression control sequence appropriate for expression of the protein in a desired host. Proper assembly can be confirmed by nucleotide sequencing, restriction mapping, and expression of a biologically active polypeptide in a suitable host. As is well known in the art, in order to obtain high expression levels of a transfected gene in a host, the gene must be operatively linked to transcriptional and translational expression control sequences that are functional in the chosen expression host. In certain embodiments, recombinant expression vectors are used to amplify and express DNA encoding antibodies, or fragments thereof, against human CD123 / IL-3Ra. Recombinant expression vectors are replicable DNA constructs which have synthetic or cDNA-derived DNA fragments encoding a polypeptide chain of an anti-CD123 / IL-3Ra antibody, or fragment thereof, operatively linked to suitable transcriptional or translational regulatory elements derived from mammalian, microbial, viral or insect genes. A transcriptional unit generally comprises an assembly of (1) a genetic element or elements having a regulatory role in gene expression, for example, transcriptional promoters or enhancers, (2) a structural or coding sequence which is transcribed into mRNA and translated into protein, and (3) appropriate transcription and translation initiation and termination sequences. Such regulatory elements can include an operator sequence to control transcription. The ability to replicate in a host, usually conferred by an origin of replication, and a selection gene to facilitate recognition of transformants can additionally be incorporated. DNA regions are operatively linked when they are functionally related to each other. For example, DNA for a signal peptide (secretory leader) is operatively linked to DNA for a polypeptide if it is expressed as a precursor which participates in the secretion of the polypeptide; a promoter is operatively linked to a coding sequence if it controls the transcription of the sequence; or a ribosome binding site is operatively linked to a coding sequence if it is positioned so as to permit translation. Structural elements intended for use in yeast expression systems include a leader sequence enabling extracellular secretion of translated protein by a host cell. Alternatively, where recombinant protein is expressed without a leader or transport sequence, it can include an N-terminal methionine residue. This residue can optionally be subsequently cleaved from the expressed recombinant protein to provide a final product. The choice of expression control sequence and expression vector will depend upon the choice of host. A wide variety of expression host / vector combinations can be employed. Useful expression vectors for eukaryotic hosts, include, for example, vectors comprising expression control sequences from SV40, bovine papilloma virus, adenovirus and cytomegalovirus. Useful expression vectors for bacterial hosts include known bacterial plasmids, such as plasmids from Escherichia coli, including pCR 1, pBR322, pMB9 and their derivatives, wider host range plasmids, such as M13 and filamentous single-stranded DNA phages. Suitable host cells for expression of a CD123 / IL-3Ra-binding polypeptide or antibody (or a CD123 / IL-3Ra protein to use as an antigen) include prokaryotes, yeast, insect or higher eukaryotic cells under the control of appropriate promoters. Prokaryotes include gram negative or gram positive organisms, for example E. coli or bacilli. Higher eukaryotic cells include established cell lines of mammalian origin, such as CHO cells. Cell-free translation systems could also be employed. Appropriate cloning and expression vectors for use with bacterial, fungal, yeast, and mammalian cellular hosts are described by Pouwels ef al. (Cloning Vectors: A Laboratory Manual, Elsevier, N.Y., 1985), the relevant disclosure of which is hereby incorporated by reference. Additional information regarding methods of protein production, including antibody production, can be found, e.g., in U.S. Patent Publication No. 2008 / 0187954, U.S. Patent Nos. 6,413,746 and 6,660,501, and International Patent Publication No. WO 04009823, each of which is hereby incorporated by reference herein in its entirety. Various mammalian or insect cell culture systems are also advantageously employed to express recombinant protein. Expression of recombinant proteins in mammalian cells can be performed because such proteins are generally correctly folded, appropriately modified and completely functional. Examples of suitable mammalian host cell lines include HEK- 293 and HEK-293T, the COS-7 lines of monkey kidney cells, described by Gluzman (Cell 23: 175, 1981), and other cell lines including, for example, L cells, C127, 3T3, Chinese hamster ovary (CHO), HeLa and BHK cell lines. Mammalian expression vectors can comprise nontranscribed elements such as an origin of replication, a suitable promoter and enhancer linked to the gene to be expressed, and other 5 or 3” flanking nontranscribed sequences, and 5” or 3’ nontranslated sequences, such as necessary ribosome binding sites, a polyadenylation site, splice donor and acceptor sites, and transcriptional termination sequences. Baculovirus systems for production of heterologous proteins in insect cells are reviewed by Luckow and Summers, Bio / Technology 6:47 (1988). Thus one aspect of the invention also provides a cell producing any one of the subject antibody or antigen-binding fragment thereof, or any one of the subject polypeptide. In certain embodiments, the cell is a mammalian cell. In certain embodiments, the cell is a HEK-293 or HEK-293T cell, a COS-7 cell, an L cell, a C127 cell, a 3T3 cell, a Chinese hamster ovary (CHO) cell, a HeLa cell, or a BHK cell. In certain embodiments, the cell is a CHO cell. The proteins produced by a transformed host can be purified according to any suitable method. Such standard methods include chromatography (e.g., ion exchange, affinity and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for protein purification. Affinity tags such as hexahistidine, maltose binding domain, influenza coat sequence and glutathione-S-transferase can be attached to the protein to allow easy purification by passage over an appropriate affinity column. Isolated proteins can also be physically characterized using such techniques as proteolysis, nuclear magnetic resonance and x-ray crystallography. For example, supernatants from systems which secrete recombinant protein into culture media can be first concentrated using a commercially available protein concentration filter, for example, an Amicon or Millipore Pellicon ultrafiltration unit. Following the concentration step, the concentrate can be applied to a suitable purification matrix. Alternatively, an anion exchange resin can be employed, for example, a matrix or substrate having pendant diethylaminoethyl (DEAE) groups. The matrices can be acrylamide, agarose, dextran, cellulose or other types commonly employed in protein purification. Alternatively, a cation exchange step can be employed. Suitable cation exchangers include various insoluble matrices comprising sulfopropyl or carboxymethyl groups. Finally, one or more reversed- phase high performance liquid chromatography (RP- HPLC) steps employing hydrophobic RP-HPLC media, e.g., silica gel having pendant methyl or other aliphatic groups, can be employed to further purify a CD123 / IL-3Ra-binding agent. Some or all of the foregoing purification steps, in various combinations, can also be employed to provide a homogeneous recombinant protein. Recombinant protein produced in bacterial culture can be isolated, for example, by initial extraction from cell pellets, followed by one or more concentration, salting-out, aqueous ion exchange or size exclusion chromatography steps. High performance liquid chromatography (HPLC) can be employed for final purification steps. Microbial cells employed in expression of a recombinant protein can be disrupted by any convenient method, including freeze-thaw cycling, sonication, mechanical disruption, or use of cell lysing agents. Methods known in the art for purifying antibodies and other proteins also include, for example, those described in U.S. Patent Publication Nos. 2008 / 0312425, 2008 / 0177048, and 2009 / 01870035, each of which is hereby incorporated by reference herein in its entirety. In certain embodiments, the CD123 / IL-3Ra-binding agent of the present invention have a N-terminal serine, which can be oxidized with an oxidizing agent to form an oxidized CD123 / IL-3Ra-binding agent having a N-terminal aldehyde group. Any suitable oxidizing agent can be used in step (a) of the methods described above. In certain embodiments, the oxidizing agent is a periodate. More specifically, the oxidizing agent is sodium periodate. Excess molar equivalents of the oxidizing agent relative to the CD123 / IL-3Ra- binding agent can be used. In certain embodiments, about 2-100, 5-80, 10-50, 1-10 or 5-10 molar equivalents of the oxidizing agent can be used. In certain embodiments, about 10 or about 50 equivalents of the oxidizing agent can be used. When large amount of the oxidizing agent is used, short reaction time is used to avoid over-oxidation. For example, when 50 equivalents of the oxidizing agent is used, the oxidation reaction is carried out for about 5 to about 60 minutes. Alternatively, when 10 equivalents of the oxidizing agent is used, the reaction is carried out for about 30 minutes to about 24 hours. In one embodiment, 5-10 molar equivalents of the oxidizing agent is used and the oxidation reaction is carried out for about 5 to about 60 minutes (e.g., about 10 to about 30 minutes, about 20 to about 30 minutes). In certain embodiments, the oxidation reaction does not lead to significant non- targeted oxidation. For example, no signification extent (e.g., less than 20%, less than 10%, less than 5%, less than 3%, less than 2% or less than 1%) of methionine and / or glycans are oxidized during the oxidation process of N-terminal serine to generate the oxidized CD123 / IL-3Ra-binding agent having a N-terminal aldehyde group. In certain embodiments, the CD123 / IL-3Ra-binding agent of the present invention have a recombinantly engineered Cys residue, such as a Cys residue corresponding to the 5 to the last Cys in, for example, SEQ ID NO: 54 or 56 (i.e, a Cys residue at EU / OU numbering position 442). Thus the term “cysteine engineered antibody” includes an antibody with at least one Cys that is not normally present at a given residue of the antibody light chain or heavy chain. Such Cys, which may also be referred to as “engineered Cys,” can be engineered using any conventional molecular biology or recombinant DNA technology (e.g., by replacing the coding sequence for a non-Cys residue at the target residue with a coding sequence for Cys). For example, if the original residue is Ser with a coding sequence of 5’- UCU-3’, the coding sequence can be mutated (e.g., by site-directed mutagenesis) to 5’-UGU- 3°, which encodes Cys. In certain embodiments, the Cys engineered antibody of the invention has an engineered Cys in the heavy chain. In certain embodiments, the engineered Cys is in or near the CH3 domain of the heavy chain. In certain embodiments, the engineered Cys corresponding to the 5 to the last Cys in, for example, SEQ ID NO: 54 or 56. The engineered antibody heavy (or light) chain sequence can be inserted into a suitable recombinant expression vector to produce the engineered antibody having the engineered Cys residue in place of the original Ser residue. 3 Immunoconjugates In a second aspect, the present invention also provides immunoconjugates comprising CDI123 / IL-3Ro-binding agents described herein covalently linked to one or more molecules of the cytototoxic agents described herein. In a first embodiments, the immuoconjugate of the present invention comprises a CDI123 / IL-3Ra-binding agents (including antibody, antigen-binding fragment thereof, or polypeptide comprising the antibody or antigen-binding fragment thereof) described herein covalently linked to a cytotoxic agent described herein through the e-amino group of one or more lysine residues located on the CD123 / IL-3Ra-binding agents. In a 1* specific embodiment of the first embodiment, the immunoconjugate of the present invention is represented by the following formula: caa—f-or), (LD), wherein: CBA is a CD123 / IL-3Ra-binding agent (e.g. a subject antibody or antigen-binding fragment thereof described herein above, or a subject polypeptide thereof described above), that is covalently linked through a lysine residue to Cy!; ‘W. is an integer from 1 to 20; and Cy! is a cytotoxic compound represented by the following formula: LP YE N 0. 0. HN— N oO oO | (Lla), LU > Yoox XY =N, 2, Net, Kn wD = © Oo 7 (Llal), ww” Re 0 YF =N, o. o. HN—, In ne 0a) fe) oO (11h) or 8 Oo 7 (Llb),or RE woe 8 o YX LN J =N. o o pit, N. 0 oO (T1h1} = © OT (Llbl)y or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SOsM; W’ is -NR¢', R® is -(CH;-CH;-0)s-R¥; nis an integer from 2 to 6; R¥is -H or -Me; R* is a (C1-Ce)alkyl; L’ is represented by the following formula: -NR;s-P-C(=0)-(CRaRb)m-C(=0)- (Bl); or -NRs-P-C(=0)-(CRaRb)m-S-Z5!- (B2%); Rs is -H or a (C1-Ca)alkyl; P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues; Ra and Ro, for each occurrence, are each independently -H, (C1-Cs)alkyl, or a charged substituent or an ionizable group Q; m is an integer from 1 to 6; and Z°! is selected from any one of the following formulas: A o A crag SO Ae . 0 bl); or (bl); o (b2); 0 (b3); SoM AAA " ANA " o 3 § tL A ° (b6), 0 Ty As ey 0 . & > (b7); o (b8); 0 (9); and P 0 A © ( SOM Pn AAP (b10), wherein: q is an integer from 1 to 5; and Mis H™ or a cation. In a 2™ specific embodiment, for conjugates of formula (L1), Cy! is represented by formula (L1a) or (L1al); and the remaining variables are as described above in the 1% specific embodiment. In a 3* specific embodiment, for conjugates of formula (L1), Cy! is represented by formula (L1b) or (L1b1); and the remaining variables are as described above in the 1% specific embodiment. More specifically, R®3 is a (C2-Ca)alkyl. In a 4% specific embodiment, for conjugates of formula (L1), Cy"! is represented by formula (L1a); Ra and Ry are both H; Rs is H or Me, and the remaining variables are as described above in the 1% specific embodiment. In a 5% specific embodiment, P is a peptide containing 2 to 5 amino acid residues; and the remaining variables are described above in the 1%, 2°¢ or 4 specific embodiment. Ina more specific embodiment, P is selected from the group consisting of Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N’-nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala- Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val- D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala- Met, and Met-Ala. More specifically, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D- Ala-Ala, or D-Ala-D-Ala. In a 6% specific embodiment, Q is ~SO3M; and the remaining variables are as described above in the 1%, 274, 4% or 5% specific embodiment or any more specific embodiments described therein. In a 7% specific embodiment, the immunoconjugate of the first embodiment is represented by the following formula: N. Naz Jw oy oy 0 AS pn xX nT Pass sod > | 0 0 | oS \ | J we GET, Jw ow - TN J LA Jk so. ) - a I A~He Ae _ i 21 © x \ 6 SOM =! 0. 0. Nex / E now o o Jun, ow So” - md ay hes i De i ’ > GH I J, No” > u4uY? H ap An vo My 0 Wo oonder FS { © ¢ Ju Ji, A A Fife op ’ TY Y BA > yf gh { “on Pool N: Me MeO’ 4 H > Zw 0 lo] H RA Snngfirom N: mS 0 0 v X x oN. 0, o. Neog¥ > | 0 0 Ja <A Brig 0. 0. I N- Me = ? & pet RN Aw, > Aa a Roan a JL by CIs | & OMe MeO 3 3 Pn < Xx H 2 ou SA Tan TH T= (Cm AA o o Jw, 2A A i po abe Cm ARQ) 0 o NF 7 Au, pop { os nf > | Gf AA Ju \ NS pr we 0 o SOM t H t N S. Ne CBA oy YS ~ AA v ¥ Pox © =N, 0. 0. Nef > AL old | 5 J ) hdl ~~ Jw ee “hoes cn ALITY N N / ! GH Fw Jw NY con 5h nD nd > L SX go >= = J we 1 Ro 1 Ss fcon oY YX NN x to oon > (Cn Cl | o 0 J Xx "ic TE. 1 oo 0 < Yd oon 1 a vs > \.~ ~ A, 2A J Kiron HN’ H = N' SS < Yoaco oN ” Cn Ss b J L J | = ka L J WL a SOM 4. Hoo. H nN s Nem CBA ay TK NN 4 xy % N, o. 0. N< / > So eG 0 o L ly ow 5 Ho 0 . SOM - . HN 1 THK ~ANY < nde Dl i > AL AAP, & 0 °° J , ~ L ~7 Fu, 2 Ho 0 SOsM Koon 5 s NY THK NY 8 0. 0. hey’ > om eh 5 J Fo nF NS L NN Jw °o 4 0 SOM t- Nl s. CBA , YTTRNY “yen eV ney! 3 oA | b J afin a Ns Jw RR 1 s icon ~Y THK SY R os nf > | Gf AA 0 ° i a b> ~~ pr. Pte oma mar ih 4 12 ALERTS Co J Jw oH 2 Fi Any Hes { ALTE cy Jw, Sas A NA S. NMmmCBA HN Y J ATE =N. 0. 0. ny > N- OMe oe o o L of ree | =» Jw [o} 9 SOM 1 AAA AS H TS x <A eV oy ” Coad 0 o yo | = = Jw 2 Ww . © SOM t Ni s. Nan CBA L OrTRNSAY Yo Xv © > -N 0. o. Nef Cm oe | b d Jo Ju, ~~ A ~ < Ro 1 0 wid > i X35 s oH fbeosa | Com nA - oO o | J =o So Oo x) ty 5 =. Ov on Need | = N . Jw I SOM to NINES ANA CBA 2 CO xy, © =N, 0. 0. Nex / > SHE AAP, o o J x afi: Ju, < Rh 1 oo Ly > oT Ei mn ho J) H Xx ro Co o YoY Ct 5 =. TE. Te A ow Net LZ x Ja oo ik NSN ANA CBA to <a NeW oy Cor Com a 0 oO Ju < 4 Cl. i > PPTs Ang He < 8 Se 3 Co | J) 1 ZN YX, S < Xo) i PY Ql 0 as os > = \ 7 Sw 2 g A : s Neto CBA , PPK < ~ s o Nef > HL ‘OMe IN b J L hi < N a JQ PO hy > [Sl x Jw, oy ~ o SO; Co RAR dpnihely, "8 J) < Xo” Cry 5 } NI L J wi °o Yo SOM td NE BD AY CBA v x Pe Te < =N. 0. 0. Ne / > eee o o J) Jw H Ono. Nyro x ¥ n OL N 0. 0. ry > N ‘OMe MeO’ N, | o 0 wo or H Og Oy Ap Rr CBA x ox " N 0. 0. Nef > fo I. | o 0 ww, or a pharmaceutically acceptable salt thereof, wherein Wi is an integer from 1 to 10; the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when it is a single bond, X is -H, and Y is -OH or -SOsM. In a more specific embodiment, the double line == between N and C represents a double bond, X is absent and Y is -H. In another more specific embodiment, the double line == between N and C represents a single bond, X is —H and Y is —-SO:M. In a 8% specific embodiment, the immunoconjugate of the first embodiment is represented by the following formula: cen {=o (L2), wherein: CBA is a CD123 / IL-3Ra-binding agent described in the first aspect of the present invention (e.g. a subject antibody or antigen-binding fragment thereof described herein above, or a subject polypeptide thereof described above), that is covalently linked to Cy? through a lysine residue; ‘W. is an integer from 1 to 20; and Cy!2 is a cytotoxic compound represented by the following formula: QS RIN RST 2} YF N 0. o. N=, N Coon 0 o A (L2a); Q -S. Ns re Pray YX X, / oy, XN =N 2. N= N. o o d o == (L2al); RZ wo 8-25} YX N N, o o HN—, o 0 (L2b); or ws zy YX Xx = SS Biv 0 o o (L2bl) or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-Cs)alkyl; and when is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SO3M; R*! and R*? are independently (Ci-Cs)alkyl; Reis -H or a (C;-Cg)alkyl; W’ is -NR¢', R® is -(CH,-CH,-0),-R¥: nis an integer from 2 to 6; Rk is -H or -Me; 27+! is selected from any one of the following formulas: Fo o Owed, = Ag . 0 (bl); o (b2); 0 (b3); Ay (bd); AAP (b3), (b2); SOM ~ AA %, : o oredr (b6), oO ro ~ ~~ 3 & A A, 7 hd (b7); i, ? ~ ~~ (b9); and P 0 wb ( SOM AAA oO ¢ (b10), wherein: q is an integer from 1 to 5; and Mis -H" or a cation. In a 9" specific embodiment, for immunoconjugates of formula (L2), Cy"? is represented by formula (L2a) or (L2al); and the remaining variables are as described above in the 8% specific embodiment. In a 10™ specific embodiment, for immunoconjugates of formula (L2), Cy"? is represented by formula (L2b) or (L2bl); and the remaining variables are as described above in the 8" specific embodiment. In a 11™ specific embodiment, for immunoconjugates of formula (L2), R®is H or Me; R* and R* are independently -(CH:),-(CR'R¥)-, wherein Rf and R are each independently -H or a (C:- Cs)alkyl; and p is 0, 1, 2 or 3; and the remaining variables are as described above in the 8h 9% or 10% specific embodiment. More specifically, Rf and RE are the same or different, and are selected from -H and ~Me. In a 12 specific embodiment, the immunoconjugate of the first embodiment is represented by the following formula: > I J ls ol IS SK , ; J. I ssp Nh Lo eb os Se A | J. > aye en 8 Ls fg’ ° And J. NS 0 SOM NYA CBA x * un LL vd ty Nr Cs Need. r ] : Kn MeO’ N, ys IO) wi > ot Tro, EN f Os hoy ° > Lee AQ | L ye TIO In BE ju CLs Wes S OMe MeO i ST NS L ae TIO J. ary een LI Ay Cy SE | > <s™ IO. > 2 Sepik GST a @ 7 “OMe MeO” ~ y-N. o 0 J wi H oO Sg RemefrncBa YTTY Og NO 8. f CBA ryt ¥ Ls CNN | Com eS o o ) we Argo Sigr sy ffencon X ha Dod ==. 0. 0. Nowy > 0h ‘OMe wl | 0 o w X | SoM Aspire cea x ° Y H =N. o. ON > f : en or o ° we 30 SOM > H ONO Sig Hfecan Te Net oo Newy¥ > ow BOG 0 o wi or a pharmaceutically acceptable salt thereof, wherein Wy is an integer from 1 to 10; the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when it is a single bond, X is -H and Y is -OH or -SOsM. In a more specific embodiment, the double line == between N and C represents a double bond. In another more specific embodiment, the double line == between N and C represents a single bond, X is —-H and Y is —SOsM. In a 13" specific embodiment, the immunoconjugates of the first embodiment is represented by the following formula: cBA +o), wo), wherein: CBA is a CD123 / IL-3Ra-binding agents described in the first aspect of the present invention (e.g. a subject antibody or antigen-binding fragment thereof described herein above, or a subject polypeptide thereof described above), which is covalently linked to Cy™* through a Lys residue; ‘WL is an integer from 1 to 20; Cy"? is represented by the following formula: \ . Q Mc 9 vX Ri Re MeO, an _ 0 = TNR MeO HO H m’islor2: R; and Ry, are each independently H or a (C,-Cs)alkyl; and 27°! is selected from any one of the following formulas: J oO A era J Ag . 0 (bl); Oo (b2); 0 (b3); 5 AAA (b2); SOM ~ AA %, : o 3 BLE PU dor (b6), 0 pt SN 4 TY hd (b7): o (b8): and (9), J ? 0 A o [{ wherein: q is an integer from 1 to 5; and Mis H® or a cation. In a 14 specific embodiment, for immunoconjugates of formula (L3), m’ is 1, and Ry and R; are both H; and the remaining variables are as described above in the 13 specific embodiment. In a 15% specific embodiment, for immunoconjugates of formula (L3), m’ is 2, and Ri and Ry are both Me; and the remaining variables are as described above in the 13" specific embodiment. In a 16" specific embodiment, the immunoconjugates of the first embodiment is represented by the following formula: Q Noe S$ § NCBA I v3 SOM eo, N . ~~ LA ved HSN © J wi wt COWL Cr, LX med HE NO Ju sor Q 0 aq qo” y H N § o YOY “NY A fo 0 a3 XA ® < eo “YY > LA = med’ nd N © “sn J Cw 0 2 yO Ko 0 $F 0 NY a vj] 10 0 < wea RY > _ 0 ~ Med re yo © # wi or a pharmaceutically acceptable salt thereof, wherein Wy is an integer from 1 to 10. In a 17% specific embodiment, for immunoconjugates of the first embodiment, M is H*, Naor K*; and the remaining variables are as described above in any one of the 1% to 16™ specific embodiment or any more specific embodiments described therein. In any of the above 1% to the 17% specific embodiments, the subject antibody or antigen-binding fragment thereof may have one or more of (e.g., substantially all of, or 100% of) the Lys residues in any of the six light chain and heavy chain CDR regions (if any) substituted by Arg. The subject antibody or antigen-binding fragment thereof may comprise an immunoglobulin heavy chain variable region (HCVR) having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and an immunoglobulin light chain variable region (LCVR) having the amino acid sequence set forth in SEQ ID NO: 41. The subject antibody or antigen-binding fragment thereof may also comprise an Ig HCVR having the amino acid sequence set forth in SEQ ID NO: 34; and an Ig LCVR having the amino acid sequence set forth in SEQ ID NO: 35. The subject antibody or antigen-binding fragment thereof may further comprise an Ig HCVR having the amino acid sequence set forth in SEQ ID NO: 32, 34, 38, 39, or 40; and an Ig LCVR having the amino acid sequence set forth in SEQ ID NO: 33, 35, 37, or 41. In certain embodiments, the second residue from the N-terminus of SEQ ID NO: 34 is Phe, while in certain other embodiments, the second residue from the N-terminus of SEQ ID NO: 34 is Val. The immunoconjugates described the first embodiment or any specific embodiments descried therein can be prepared according to any methods known in the art, see, for example, WO 2012 / 128868 and WO2012 / 112687, which are incorporate herein by reference. In certain embodiments, the immunoconjugates of the first embodiment can be prepared by a first method comprising the steps of reacting the CBA with a cytotoxic agent having an amine reactive group. In one embodiment, for the first method described above, the reaction is carried out in the presence of an imine reactive reagent, such as NaHSOs. In one embodiment, for the first method described above the cytotoxic agent having an amine reactive reagent is represented by the following formula: Rat vx N, 0. 0. HN—y N. 1 ° (L1a%), Lo, YX XOX N 2. bol N ° S fecal oO oO (Lla’l), RS ww” c—E o \ =N, 0. o. Ey 0 o 111, AF (L1b%), or 3 ww” Ree « o Y, } X x =, o. 0. N=, 0 0 (L1b’1); or a pharmaceutically acceptable salt thereof, wherein: L* is represented by the following formula: -NR;s-P-C(=0)-(CRaRp)u-C(=0)E (BI); or -NR;s-P-C(=0)-(CRaRb)m-S-Z° (B2) C(=O)E is a reactive ester group, such as N-hydroxysuccinimde ester, N-hydroxy sulfosuccinimide ester, nitrophenyl (e.g., 2 or 4-nitrophenyl) ester, dinitrophenyl (e.g., 2,4- dinitrophenyl) ester, sulfo-tetraflurophenyl (e.g., 4-sulfo-2,3,5,6-tetrafluorophenyl) ester, or pentafluorophenyl ester, preferably N-hydroxysuccinimide ester; Z is represented by the following formula: esented by the rollowing rormula: 0 3 u I~ on 7 Q Zr ree Ly 0S (al); ° o (a2); o SY Hg (a3); 0 AY 0 o ( o SAN ’ o aq [¢ 0 SOM 0 “Y- ANY ‘ o (a4); ° of : 0 2 0 8 CID Sr rr 0” { 0 (a6), o 9 J Y A : \ AALS ~ Aer 0 @) © CO (a8): A 0, o rN 0 A u (a9); and oM 0 wR l, o oO {( (al0), wherein: q is an integer fro 1 to 5; and U is =H or SO:M; and the remaining variables are as described in any one of the 1% to 7* and 17% specific embodiments or any more specific embodiments described therein. In certain embodiments, the immunoconjugates of the first embodiment can be prepared by a second method comprising the steps of: (a) reacting a cytotoxic agent with a linker compound having an amine reactive group and a thiol reactive group to form a cytotoxic agent-linker compound having the amine reactive group bound thereto; and (b) reacting the CBA with the cytotoxic agent-linker compound. In one embodiment, for the second method described above, the reaction in step (a) is carried out in the presence of an imine reactive reagent. In one embodiment, for the second method described above, the cytotoxic agent- linker compound is reacted with the CBA without purification. Alternatively, the cytotoxic agent-linker compound is first purified before reacting with the CBA. In certain embodiments, the immunoconjugates of the first embodiment can be prepared by a third method comprising the steps of: (a) reacting the CBA with a linker compound having an amine reactive group and a thiol reactive group to form a modified CBA having a thiol reactive group bound thereto; and (b) reacting the modified CBA with the cytotoxic agent. In one embodiment, for the third method described above, the reaction in step (b) is carried out in the presence of an imine reactive reagent. In certain embodiments, the immunoconjugates of the first embodiment can be prepared by a fourth method comprising the steps of reacting the CBA, a cytotoxic compound and a linker compound having an amine reactive group and a thiol reactive group. In one embodiment, for the fourth method, the reaction is carried out in the presence of an imine reactive agent. In certain embodiments, for the second, third or fourth embodiment, described above, the linker compound having an amine reactive group and a thiol reactive group is represented by the following formula: Np 2 formula: 0 o ody O=N, ~ rr 7 0, Of oy . 0 oO (all); © o (a2L); (a3L); 0 0. @ ad x . 1 0 of (a 0 QML so o o. i” ANY y , ° : o (adL); 7 [dd (aSL), 0 0. ~N, NY ¥ . o of [€ 0, 0 Q Q 3 fi nL ASA Sry N { 0 (abL), o Q 0 2 o x J 7 0 Nr oy g ANA Tr NY 0 (a7). © 0 n nN 0 0 (Jl); © O (@sL): oO oO YA 0 1 , J \ o \ u (a9L); and SoM 0 0. ~N AA A o I~ 0° { (alOL), wherein X is halogen; Jo ~SH, —SSR¢, or -SC(=0)R&; R¢ is phenyl, nitrophenyl, dinitrophenyl, carboxynitrophenyl, pyridyl or nitropyridyl; RE is an alkyl; and the remaining variables are as described above for formula (al) — (al0); and the cytotoxic agent is represented by the following formula: Q ~SH RY PR N % > N, 0 0 HN—, N. 0 0 ” [o} -SH Re, SR N Y, X XX 5 DL, N=, Oo oO + RX ww sH Y, X =N o. o HN—, N 0 0 . 0 — sor RZ we SH yx Xo y A LO, pot N en, o o or a pharmaceutically acceptable salt thereof, wherein the variables are as described in any one of the 8" to 12% and 17 specific embodiments and any more specific embodiments described therein. In certain embodiments, for the second, third or fourth methods described above, the linker compound having an amine reactive group and a thiol reactive group is represented by any one of the formula (alL) — (alOL) and the cytotoxic agent is represented by the following formula: o WN SH 0 m av9 9, Ri Re MeO, OY _ 0 = Pho MeO HO H rn Acetone d Alcon fen mercy marmot n 12th em 1 Wherein the variables are as described above in any one of the 13 to 17% specific embodiments and any more specific embodiments described therein. In a second embodiment, the immuonoconjugate of the present invention comprises an oxidized CD123 / IL-3Ra-binding agent (including antibody, antigen-binding fragment thereof, or polypeptide comprising the antibody or antigen-binding fragment thereof) described in the first aspect of the present invention described herein (e.g., oxidized antibody or antigen-binding fragment thereof, or the polypeptide thereof) covalently linked to a cytotoxic agent described herein through one or more aldehyde groups located on the oxidized CD123-binding agent. The aldehyde groups located on the oxidized CD123 / IL-3Ra- binding agent can be generated by oxidizing one or more 2-hydroxyethylamine moiety of the CDI123 / IL-3Ra-binding agent, wherein the 2-hydroxyethylamine moiety is part of a serine, threonine, hydroxylysine, 4-hydroxyornithie or 2,4-diamino-5-hydroxy valeric acid residue. In one embodiment, the aldehyde groups can be generated by oxidizing the 2- hydroxyethylamine moiety of one or more N-terminal serine residue(s) located on the CDI123 / IL-3Ra-binding agent (e.g., 1, 2, 3, or up to 4 Ser residues at the N-termini of the light chains and / or the heavy chains). In a 1% specific embodiment of the second embodiment, the immunoconjugate of the present invention is represented by the following formula: osavkics—oy!) I'S (S1); wherein: CBA is the oxidized CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject oxidized antibody or antigen-binding fragment thereof described herein above, or a subject oxidized polypeptide thereof described above); Wsis 1,2, 3, ord; Jen’ is a moiety formed by reacting an aldehyde group on the CBA with an aldehyde reactive group on Cy®!, and is represented by the following formula: H 9%. H RE 2 Ten ar A a AS ee, uae N A fe $13—C=N~ s1§—C _K. NN s $-C=N., s13—C _K. N — 3 $ H N ¥'s2 $2 H N—% s2 N—% s2 sig H ~eMo-} s2 - Hy sis 3 ~e=N, c=Ng_ 5 oO } 2, or wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cyl; Cy! is represented by the following formula: Foy ORR Zor (eRARY—} o YX N OL, NT Kn wy 0 (S1a), For Np ORR —2Ze (CRA o YY, X Xo =N. fo o eet, 0 ( el. 8 Oo (Slal), RS wo e—L— o LB =N, o. o. N= om WAY o o IRR wr = 0° OT (Slb),or Re wel © Y X X y =, 0. o. Nest, Im WA o o (QTR) = © oT (Slibly or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SOsM, and Mis H" ora cation; Rs is -H or a (C1-Ca)alkyl; P is an amino acid residue or a peptide containing 2 to 20 amino acid residues; Zq) is absent, -C(=0)-NRy-, or -NRg-C(=0)-; Ry is -H or a (C;-Ci)alkyl; R. and Ry, for each occurrence, are independently -H, (C1-Cs)alkyl, or a charged substituent or an ionizable group Q; rand r’ are independently an integer from 1 to 6; W’ is -NR¢', R® is -(CH,-CH,-0).-R%; nis an integer from 2 to 6; R¥is -H or -Me; R® is a (C1-Co)alkyl; L is -NRy-(CRaRb): or absent; and 1” is an integer from 0 to 6. In a 2™ specific embodiment, for immunoconjugates of formula (S1), Cy*' is represented by formula (Sla) or (Slal); and the remaining variables are as described above in the 1% specific embodiment. In a 3% specific embodiment, for immunoconjugates of formula (S1), Cy*' is represented by formula (S1b) or (S1b1); and the remaining variables are as described above in the 1% specific embodiment. More specifically, R®3 is a (C>-Ca)alkyl. In a 4% specific embodiment, for immunoconjugates of formula (S1), Ra. and Rs are both H, and Rs and Ry are both H or Me; and the remaining variables are as described above in the 1° or 2™ specific embodiment. In a 5 specific embodiment, for immunoconjugates of formula (S1), P is a peptide containing 2 to 5 amino acid residues; and the remaining variables are as described above in the 1%, 27¢ or 4th specific embodiment. In a more specific embodiment, P is selected from the group consisting of Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, lle-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala- Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val- Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala- Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. Even more specifically, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In a 6% specific embodiment, for immunoconjugates of formula (S1), Q is -SOsM; and the remaining variables are as described above in the 1%, 224, 4% or 5% specific embodiment. In a 7% specific embodiment, the immunoconjugate of the second embodiment is represented by the following formula: 0-4 xX Q 9 u H AN A Aho N - HN N=¢mtcBA TH o 0-4 ft x H N 0. 0. Ney” > o d “ws ; "4 o 9 H H AM A Art NN =cmtcBA HN Tu 3 a Ft ¥ x 3 A ew Ney” > Cm meg 0 o ) 2 ws ; 0-4 0 9 H H AA A Ania N HN N N—CamrCBA TH 0 04 H a X Y fl 0. o. Nef > $o! OMe Neg: o o F N wg . 5 " i 1 HN NS ~NSg CBA x AN 0 0 0-4 Hy ] Zy x w \ 2 H H Ho: i 1 N RE ¢ ~N SN—cmbeaa og TN I -N ¥ x 3% Ol. fog? > Cn et i © 0 J “ws fn f NO N Ay = 2 TN N py o o X Y f eo Nef ” % Ce wa 0 0 af NA N- Js : i Joplin N N= pry v= < qr -- NH No ALO. I I le LEN NST > 9 H RA N Bri awd mdi NaN tgposs o o x X Yael Nel Ney” > Cm wl oO o Jj 7 we AAPA Age < N Oe hr > a “50, { 5 d NA ~~ Js ° uy. f H a ANA SS NN SN embcBA oH ° AH, % PY 3 [o} 9 y H Ho 0. N. An NN meer 0 a X o o 2 wx X N o o New > Cm wl o o y “ws > 9 H J HAI AA, HN =C CBA of 0 gt x N o o Ney’ > Ce WH ry , < ws arb LH hn o o H xX A Nv 1 > 9 A ps Ani HN N =C~rCBA o " ° it x X Yi 0. 0. Ness > Cm my 0 0 0) J ws : o ? A BN Hy N N—C CBA o H o H ff Xx H < N o o Nes” > Son Nels | 0 0 0) y a; ws : oon H LH jo] 0 xX I wv 0 A A Ani N —CmrCBA TH o A 1 x X / | Cw wl oT 0 4 n xX " Zz : R fl X SN=¢ foes SIN ~TN, c Oo xX P < HN a UO) Jo BO. AS > La nr | 0-4 oO X 7 | < N ls N= / ~ lam! N OMe MeO’ N, ys J 2 ws H x A © x | | > H H 0 0 N Nn AON NEON N= o NY ~TN fo 1 © Ly Y. | ACA ’ MM N OMe MeO N o o J J ws Og ~N N 0. N Nog G NY ; CCBA XxX < R a OY Job BO. AS > Eo w- | a ° x, 0-4 < i 0. 0. N= / AL fo N OMe MeO’ N ys J Qo YY ¥ Nv ; ab, ee P J « 0-4 H < od oO Jo Oo es” > a INF xX ws R R OSA SO N SN— o NSN TN, N ff-oe» x °c oxy < or 0. 0. Nex / > / N OMe MeO N oy 2) J NF xX ) Ws R o 0. 0. NTN SN= AON SNS N gms H he 0 xX < RR CY Jo IL TO. A > LCC 0 i IY ( OMe wl ey x 2 © 0X < Yd ~~ O Jo OY om AY > Nae 3 LN” xX J . Ws NO O. 0. N= AONENOAINAN N — ; * x < or 0. 0. Nes’ > / m Cn ee 1s ey J] / ws H a 0. 0. NoS-O~ AON NEN N—C CBA 0 ~Y N8 Z X H | < Rs a 6 NY > iL CL 0 i | of { OMe AL0 o x - © < YON he HY Jo IL Ay. A AY > 75 NF xX . / ws 0. FO OSA ON SN— o NY N goes YX ° x < or o oa Net > OG CC N OMe MeO N 1s 0 J] Xx ) ws R Sn= cBA eat SR SSS N=CH fn A 0 yx Z Ty H I < > ~ ow 3 LL Jimi i Xx < R Qs Nef ' > A / ™ N OMe MeO N TY ™g A © Wg y NO NONI NT SNH anf x A Oo x 1! < EN AOS AO AN H N Briers DSS “NN=CH foe CBA ) 2. ’ : Y | NN < N © 0. Nef > AL / M N OMe MeO N | o o HF Wg H N PRS SSS SN-CHppecA A 0 Ny > =m Meme em le = NE cof H | Y N 0. 0. N= / 5 =i mM N OMe MeO N ot J J Ws sor H xX. 1 < ENA AO ANS i N ARNG Agr SNcHpmpeceA y : 2 ’ { Y < -N o o Nef x am N OMe MeO N | oO o oF © Ws or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or -SOsM. In a more specific embodiment, the double line == between N and C represents a double bond, X is absent and Y is -H. In another more specific embodiment, the double line == between N and C represents a single bond, X is —H and Y is —SO3M. In an 8 specific embodiment, the immunoconjugates of the present invention is represented by the following formula: codigos) ($2); wherein: CBA is the oxidized CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject oxidized antibody or antigen-binding fragment thereof described herein above, or a subject oxidized polypeptide thereof described above); Ics’ is a moiety formed by reacting an aldehyde group on the CBA and an aldehyde reactive group on Cy*2, and is represented by the following formula: Ho H i il st Fea fe, s1§—c Hy fo, st Feta " Hy sor Roe y bad ’ tad H, H ste sig H C —N Ne=N Ne—N s1 “Ni 2 7 ~o—} ” a ~o— @ 4 sor wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy; Cy* is represented by the following formula: HN—, Q, -S. Re, PR Sur N Y, EF =N o o HN—, 0 Oo = 0 Oo 7 (Sa); Q .S Re D—R Sud SN YX X x -N, Sey N=, 0 Oo (L291) = 0 OT (S2al); R2 ws} y F =N o. o YN, Oo 0 (QIRY. Ar = © OT (S2b)or RZ ww” s-L—} Y, X X Y -N OL. N=, Se CLAD oO oO (L'%M1Y) = © Oo TT (S2bl), or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-Cs)alkyl; and when is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SOsM; Mis H' or a cation; R*! is a (C1-Ce)alkyl; Reis -H or a (C,-Ce)alkyl; W’ is -NR¢, R® is -(CH;-CH;-0)s-R¥; nis an integer from 2 to 6; Rk is -H or -Me; R*2 is a (C1-Ce)alkyl; L, is represented by the following formula: Raz Q by the 1ollowing formula: Ra Ras 0) z 3 a2, ~~ sd a | m Ra. Ra Q wherein: s3 is the site covalently linked to the group Jes’; s4 is the site covalently linked to the -S- group on Cy*2; Za is absent, -C(=0)-NRy-, or -NRy-C(=0)-; Ro is -H or a (C1-Ca)alkyl; Q is H, a charged substituent or an ionizable group; Ral, Raz, Ras, Rus, for each occurrence, are independently H or (C1-Ca)alkyl; and ql and rl are each independently an integer from 0 to 10, provided that q1 and rl are not both 0. In a more specific embodiment, Zs; is absent; q1 and rl are each independent an integer from 0 to 3, provided that q1 and rl are not both 0; and the remaining variables are as described above in the 8% specific embodiments. Even more specifically, Rai, Raz, Ra3, Ras are all -H. In another more specific embodiment, Zs; is -C(=0)-NH-, or -NHy-C(=0)-; q1 and rl are each independently an integer from 1 to 6; and the remaining variables are as described above in the 8 specific embodiments. Even more specifically, Rai, Raz, Ra3, Rus are all —-H. In a 9 specific embodiment, for immunoconjugate of formula (S2), Cy*? is represented by formula (S2a) or (S2al); and the remaining variables are as described above in the 8" specific embodiment or any more specific embodiments described therein. In a 10™ specific embodiment, for immunoconjugate of formula (S2), Cy*? is represented by formula (S2b) or (S2b1); and the remaining variables are as described above in the 8% specific embodiment or any more specific embodiments described therein. In an 11% specific embodiment, for immunoconjugate of formula (S2), -Li- is represented by the following formula: 2 OM 3K AL s4 ; % Ans 4 3 S—]] é, oh ee fs Hw R N wa uy R H ~ FA y | R R For A ine 4 EAA # o ; or o or a pharmaceutically acceptable salt thereof, wherein R is H or -SO3M; and the remaining variables are as described above in the 8%, 9% or 10™ specific embodiment or any more specific embodiments described therein. In a 12% specific embodiment, for immunoconjugate of formula (S2), R¢ is H or Me; and R*! is -(CHz)p-(CRRY)-, and R*?? is -(CH:),-(CR'R®)-, wherein Rf and R are each independently -H or a (C1-Cs)alkyl; and p is 0, 1, 2 or 3. More specifically, Rf and Re are the same or different, and are selected from -H and -Me. In a 13% specific embodiment, the immunoconjugate of the second embodiment is represented by the following formula: 0 0 =c-c SYN a BA R L. r N < o. N= IC Nr "ome MeO SS o 0 Fig 0 0 N=C+~CBA OPEN NY 5 YX X y > =A. Lon nN o 0 Five J we o 5 0 i la 3 SETTER, o 0 H N—GpwCBA a AY i v, KX ad Re ethpeeu o o 3 we NY o W Jw Ae AA i HN 7 SN CBA { Ca fy ’ t i ry ‘, nJ o oo Cows 2 f MNP “=n YX xX ¥ o Lon nd ’ { py 0 o _ £ few s. a SY Syn ¥ fi Lo , > ST ° o oo ~~ - Ws 9 H = Nye omnia HN 7, ~~ Y N N - Xx & YX f iy =N. 2 0. FZ N N=, > Nome Meo” O o o a Ws } ATR A STIR YY © SN 7 Ws SOM i I AN rt can X Tx ° Y, 5 A Con Nt > o o 2 0 - Ws o SOM H YN AA Se CBA % 8 5 HH H Xx N o. o. N= > o o , 0 B Ws 0 SOM 1 s NS HN 7 Sg N—C nonneCBA oy H Hy v, X X x ° N o. o. N= > {OTe o o | B ws LA ge HN SN SNC vp CBA , Y MY N= H N. 0. 0. tf > Fen wn L 0 o a = F ws J [7 £ { 8 S, SN=CdwCBA yr TY ly N wr Xx yk Y =N. Loo — > Cr I tw _H Cry press Seal ~~ hd 0 Ws Aves ~~ ff HN “YS Hi wf ’ Xx ° " = N= > XK nee lL 5 ° i NS N. 0. N=, > &- Ko XR NR r= J ws o OM H mee AY gen “> -4 vf Xy © oN. o 0. Nef > roe Cry bh. Th a il. a ws SOM fe &- Ka A WJ Ay - FonSon, dic 4 o Ws CRY AA nego Net ee eos NA OANA ONAN > SET ngs IA ge ) "A OL. te ‘ JNA OA ONAN > Se PR L © 0 J ve | &- T ‘OMe MeO’ T 5 xX NAN AOA AO AAN > GHEE i. =. AAO: N= > L Ao i o 0 Jw Ane ASH 2 ~ Ss NS og Y x 1 H f o. o N= > Sen Wey | 5 8 | N. OAC: N=, NN © oo 7 Jw . a SOuMy o s N N= a ~Y NNN os ‘ o YX Xz N a N= > : o o I NN’ © 0 7 Jw 0 SOM}, YIN NNN cea H ty © ! N. 0. 0. Ned > N OMe wl } ° 0 STIR, Wg ° SO3Myy fee S, MNOS —cmcea oS I H Fy x x Y, ¥ <x -N. Os Nf > } ° 0 )eN. OAL: N= > 0 75 AA n=l nducaa ' AE LP 1 SIETTLIRy we 0 Ape HN 4 SIN ANC re Xx £OM 0 toa Cat . Ke EE L o 0 |. ws > 0 H s. N. H adage ~sN notions w ¥ J 7 Fou Y =A. 0, 0. Nf > L ° ° le Jus > 0 H Ha wri A Joon x : x FOM © X A o. N= > i ° ° le Jue H 0. 0. s N AON NON ~~. jo 0 x NN N freon x H R % =N 0. 0. Nes, > @ G ce we? C & o o Wg H 0. 0. s N AOA ~NTX STN SNgfosa H v. % |x © =N o. 0. Nef > @ i” - i. 2 oo o o Ws s y OOO STN SN—c: CBA ” I H Hy | H < YON 0. 0. N—, > CoC o o < HN NA OANA x f 0. N= > Ws { 0. 0. S. ONO ~~ NN SN—c CBA x S$ HF X X oy 6 YN 0. 0. Ne= / > Clon wl 0 0 Ws SOM ‘ A NR NN SNT=G fw CBA X 5 H Y. J i < CC TX > N OMe MeO N, 0 0 7] Wg SOM i OOO HI ong N=, c CBA x H Yo 9 B =N 0. 0. Nes > Ney : OMe MeO 8 @ o o l Wg SOM ‘ 0. o. Ss. AON Oy ~~ AN fi CBA KT ah x o ¥ J H < » Sel Non, > Cen wl 5 oO o + Tk < YN PN oANAO N= > Wg SoM N NIA SI NN ry CBA x x ° ho Yo \ =N 0 0 Ney” > lon wo o o Ps Ws AON HIN NTN pH X Yer Sel N ” N N— < rr 5 2 3 Fas N OMe MeO N, 1s J Wg > I S. |—— POS Ne NTN a X X j Y =N Is Ney a / N OMe MeO N. | 0 0 < FINN ON AO NX Im Ws 0. 0 s R—c CBA ONO INN No NN rf Xx | H < Yen Ol, N~, ” / ™\ N OMe MeO N | 0 0 \ oy > I~ Ws OO Ss. f—c CBA - 0 NC No NTN Ha X A , " ° © Ney! ” / M N OMe MeO N, | o Oo 1 I. CoM < Ws 0. 0. s N—C CBA AOA NC ~~ NN —5 Xx tom © | H < "N Ola Ness, is em oa o o Wg 1 | CoM iN com ~ \ 2! Ne > H N N—C: CBA Ar SB Bo, NN 2 =g1 x X tom © | \ 2 Y =N. Ol. Neg? > Cen SoG o o 1 I. CoM < 7 Ye bs Ws R H s N—C: CBA AON gp No i I. x com © | H 2 <p el ey r fod le y of C . 0 0 | tom Ya hie Ws o o s R R—cmmcan Arsene, SN he A v x o 2. Me! bom > ‘ en AL 0 0 . - Ws o HGS, J Agrees s N X | H "yen Js Me 4 Mm N OMe MeO N, oO o We Wg Hn > o NOAH IN NN A Y, x X Y i > =N 0 lo N= mm N OMe MeO N o 0 We Ws < oF H 0. 0. Ss N—C CBA AON NO Ne a ~ N H . KX N 2 | H < Ne o o N—, CC acs o 0 J Wg Ws sor CX A I o H 0. 0. S. AU N—C CBA Oo NTC ~¢ NT I x A ! NN 0. 0. Ney” N~( . OMe MeO : a 0 0 7 Wg | NF x Cows or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when it is a single bond, X is -H; and Y is -OH or - SO3M. In a more specific embodiment, the double line == between N and C represents a double bond, X is absent and Y is -H. In another more specific embodiment, the double line == between N and C represents a single bond, X is -H and Y is -SO3M. In a 14% specific embodiment, the immunoconjugate of the second embodiment is represented by the following formula: 3 —Cy* ).. Jes! ade CB, (S3); wherein: CBA is the oxidized CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject oxidized antibody or antigen-binding fragment thereof described herein above, or a subject oxidized polypeptide thereof described above); Ics’ is a moiety formed by reacting an aldehyde group on the CBA and an aldehyde reactive group on Cy, and is represented by the following formula: = iy He HN 2 1 C=N. s1 Fe=ry 7, s1 fc ty 7, 5 Fe “NH = sor Sm gf H #82. H 1 H #82. HH H, H sig ’ s1f—c’-N * Ne=N NH pte Boode Roo x jor 2 wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy; Cy* is represented by the following formula: tESLIIICU DY UIC I0110WIlE 101111U1d. o N S. > a] the L—j Cl \ ? 3 ° R; Re MeO, MARL rN Sy A “een ved HE N o wherein: m’'islor2; R, and Ry, are each independently H or a (C,-Cs)alkyl; L, is represented by the following formula: Rez Q by the tollowing formula: Ras, Ras s3 Za RN at i rm Rs Raz Q wherein: s3 is the site covalently linked to the group Jes’; s4 is the site covalently linked to the -S- group on Cy*3; Za is absent, -C(=0)-NRo-, or -NRy-C(=0)-; Ry is -H or a (C,-Cj)alkyl; Q is H, a charged substituent or an ionizable group; Rai, Raz, Ras, Ras, for each occurrence, are independently H or a (C;-Cs)alkyl; and ql andr are each independently an integer from 0 to 10, provided that q1 and r1 are not both 0. In a more specific embodiment, Z,» is absent; q1 and rl are each independent an integer from 0 to 3, provided that q1 and rl are not both 0; and the remaining variables are as described above in the 14% specific embodiments. Even more specifically, Ral, Raz, Raz, Ras are all -H. In another more specific embodiment, Zz, is -C(=0)-NH-, or -NHy-C(=0)-; q1 and rl are each independently an integer from 1 to 6; and the remaining variables are as described above in the 14 specific embodiments. Even more specifically, Rai, Ra2, Ra3, Ras are all =H. In a 15% specific embodiment, for immunoconjugates of formula (S3), m’ is 1; Ri and Ry are both H; and the remaining variables are as described above in the 14 specific embodiment or any more specific embodiments described therein. In a 16™ specific embodiment, for immunoconjugates of formula (S3), m’ is 2; R; and R: are both Me; and the remaining variables are as described above in the 14 specific embodiment or any more specific embodiments described therein. In a 17" specific embodiment, for immunoconjugates of formula (S3), -Li- is represented by the following formula: 9 com | LAL ol. 3 / 2 5 As “ I ~| 3 R R SrA Ans 2 s4 oO sor Fondo hm s4 r 0 or a pharmaceutically acceptable salt thereof, wherein R is H or -SO:M and Mis H" or a cation. In a 18" specific embodiment, the immunoconjugate of the second embodiment is represented by the following formula: contin, Ls s Ag | A ws, 3 osafor, A, PN s Ay | N © J Ws. 0 CBA: —N, += WO Se { 0M 3 Hoar =U;M O J We Ss. gy 0 tod NSA | OM ) CL SUM : - 4 Ws. contin t ~Ho I J Ws / \ Jug, u 0 opag—g—H, ANN ES on I J Wg, Bh 2, Jug. H 0 rion oe 2 J O CoH / N\ Jug. 0 H H CBA——C—N, N, TN NN O,H J Wa QO $ COH / N\ dum, or a pharmaceutically acceptable salt thereof; wherein DM is represented by the following formula: Me, \ SN 0 Nt 0 A Cl \ V MeO, AARL, ’ CN Y Ao SESE ny ved Hd N o In a 19% specific embodiment, the immunoconjugate of the second embodiment is represented by the following formula: candice —cr*) (S4) wherein: CBA is the oxidized CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject oxidized antibody or antigen-binding fragment thereof described herein above, or a subject oxidized polypeptide thereof described above); Jeg’ is a moiety formed by reacting an aldehyde group on the CBA and an aldehyde reactive group on Cy** and is represented by the following formula: — a s1 §—C=N, § 2, J s1 C Ye, st fo=ney ' + = A NN is2. HT §s2 H sor ! Ney HH Poy © ; o— 2 st jc “Sn 2 Ce - wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy; Cy* is represented by the following formula: NL NTN 0 N- Qo oO cl ON OMe MARL rN (S4a), Y A 0 SPN A ome oHNH 0 L:’ is represented by the following formula: s3 2, Z s4 “ wh Re! Ry © . sor E Z s4 2 02, 2 $3 Zs Ene —N SY i Rs Ri oo Ros Rua wherein: s3 is the site covalently linked to the group Jes’ group; s4 is the site covalently linked to -NMe- group on Cy*; Zp and Zy; are both absent, or one of Zp; and Zs; is absent and the other is -CH2-O- or -0-CHs-; Zv1” and Zy2’ are each independently absent, -CH>-O-, -O-CHz-, -NRy-C(=0)-CHa-, or -CH-C(=0)-NRo-; Ry is H or (C;-C3)alkyl; nl and m1 are each independently an integer from 1 to 6; one of E; and E; is -C(=0)-, and the other is -NRy-; or one of E; and E; is -C(=0)- or -NRg-, and the other is absent; P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues; and Roi, Roz, Ruz, Res, Ros and Res, for each occurrence, are each independently H or a (C1-Ca)alkyl. In a 20" specific embodiment, for immunoconjugates of formula (S4), Rol, Rez, Res, Ros, Ros, and Reg are all H; and the remaining variables are as described above in the 19™ specific embodiment. In a 21% specific embodiment, for immunoconjugates of formula (S4), Ry is H; and the remaining variables are as described above in the 19% or 20% specific embodiment. In a 22™ specific embodiment, for immunoconjugates of formula (S4), Zy:’ and Zp’ are both absent; or Zy1’ is -CH2-O- and Zs’ is absent; or Zp; is -CH2-C(=0)-NRo-; and Zs’ is -O-CHa- or absent; and the remaining variables are as described above in the 19%, 20% or 21% specific embodiment. In a 23 specific embodiment, for immunoconjugates of formula (S4), P is a peptide containing 2 to 5 amino acid residues; and the remaining variables are as described above in the 19, 20%, 21% or 22™ specific embodiment. In a more specific embodiment, P is selected from the group consisting of Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°- nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala- Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe- Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala; and the remaining variables are as described above in the 23" specific embodiment. Even more specifically, P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In a 24" specific embodiment, the immunoconjugate of the second embodiment is represented by the following formula: o ant Ja, f 5 Jw, 1 " 0 cBACH, Ny a ' S Jws, o ] J ws H caat—c—N PO Hy No om f 5 Jw, : H H | DM a | J wg 9 H H H CH,—| cer > AA Enno H H 0 0 Tvs, 2 ou] 2 Ay 0 OA Ny NIN NY IN, corny Jus, om A, 1 0 Hoof , afcH; y cs ws, ig | 9 yu AN oY H AN N Ny NCH N N. coon ws, DM | q LAA A one R NY ll H Ni y NY J ws, + ol N. N. DM ~N ‘ Hh Nr hs Yo X No~, I CBA Noy N N ws, DM . Kimo 0 : hy Mond I H YoY C—| oBA—G- ws, y 9 - CRAG AA on | 5 J ws, L o 2 H NA A NY ws, 3 DM CBAE=N. Y | ws, 3 H —N DM Cl © 01 l ws, or a pharmaceutically acceptable salt thereof, wherein DM is represented by the following structural formula: Me, \ Ao TR \ 0 Nt ° ~~ Cl \ V MeO, MARL, | o_o i] © 1 Lo ed I «4 yo MeO HO H In a 25% specific embodiment, for immunoconjugates of the second embodiment, M is H*, Na* or K7; and the remaining variables are as described above in any one of the 1% to 24% specific embodiment or any more specific embodiments described therein. In any of the above 1* to the 25% specific embodiments, the subject oxidized antibody or antigen-binding fragment thereof may have 1, 2, 3, or up to 4 N-terminal 2- hydroxyethylamine moieties oxidized to aldehyde group(s), for linking covalently to a cytotoxic agent described herein. The N-terminal 2-hydroxyethylamine moiety may be part of a serine, threonine, hydroxylysine, 4-hydroxyornithine or 2,4-diamino-5-hydroxy valeric acid residue, preferably Ser or Thr. For simplicity, the description below, including the oxidation reaction and any subsequent conjugation with linkers or cytotoxic agents, may refer to Ser as a specific example of such N-terminal 2-hydroxyethylamine moieties, but should generally be construed as referring to all N-terminal 2-hydroxyethylamine moieties. The subject antibody or antigen-binding fragment thereof may comprise an immunoglobulin heavy chain variable region (HCVR) having the amino acid sequence set forth in SEQ ID NO: 38; and an immunoglobulin light chain variable region (LCVR) having the amino acid sequence set forth in SEQ ID NO: 33, 35, 37, or 41 (preferably SEQ ID NO: 35 or 37). The subject antibody or antigen-binding fragment thereof may also comprise an Ig HCVR having the amino acid sequence set forth in SEQ ID NO: 32, 34, 38, 39, or 40 (preferably SEQ ID NO: 34); and an Ig LCVR having the amino acid sequence set forth in SEQ ID NO: 37. The subject antibody or antigen-binding fragment thereof may also comprise an Ig heavy chain (HC) region having the amino acid sequence set forth in SEQ ID NO: 53 or 56; and an Ig LCVR having the amino acid sequence set forth in SEQ ID NO: 33, 35, 37, or 41 (preferably SEQ ID NO: 35 or 37). The subject antibody or antigen-binding fragment thereof may also comprise an Ig HC region having the amino acid sequence set forth in SEQ ID NO: 48, 50, 53, 54, 56, 59, or 60 (preferably SEQ ID NO: 53); and an Ig LCVR having the amino acid sequence set forth in SEQ ID NO: 37. In certain embodiments, the second residue from the N-terminus of SEQ ID NOs: 34, 38, 50, 53, 54, or 56 is Phe, while in certain other embodiments, the second residue from the N-terminus of SEQ ID NOs: 34, 38, 50, 53, 54, or 56 is Val. In certain embodiments, the immunoconjugates of the second embodiment can be prepared by a first method comprising reacting an oxidized CD123 / IL-3Ra-binding agent having an N-terminal aldehyde described in the first aspect of the invention with a cytotoxic agent having an aldehyde reactive group. In certain embodiments, the immunoconjugates of the second embodiment can be prepared by a second method comprising reacting an oxidized CD123 / IL-3Ro-binding agent having an N-terminal aldehyde described in the first aspect of the invention with a linker compound having an aldehyde reactive group to form a modified CD123 / IL-3Ra-binding agent having a linker bound thereto, followed by reacting the modified CD123 / IL-3Ra- binding agent with a cytotoxic agent. In certain embodiments, the immunoconjugates of the second embodiment can be prepared by a third method comprising contacting an oxidized CD123 / IL-3Ra-binding agent having an N-terminal aldehyde described in the first aspect of the invention with a cytotoxic agent followed by addition of a linker compound having an aldehyde reactive group. In certain embodiments, the immunoconjugates of the second embodiment can be prepared by a fourth method comprising the steps of: (a) oxidizing a CD123 / IL-3Ra-binding agent having a N-terminal 2- hydroxyethylamine moiety (e.g., Ser / Thr) with an oxidizing agent to form an oxidized CD123 / IL-3Ra-binding agent having a N-terminal aldehyde group; and (b) reacting the oxidized CD123 / IL-3Ra-binding agent having the N-terminal aldehyde group with a cytotoxic agent having an aldehyde reactive group. In certain embodiments, the immunoconjugates of the second embodiment can be prepared by a fifth method comprising the steps of: (a) oxidizing a CD123 / IL-3Ra-binding agent having a N-terminal 2- hydroxyethylamine moiety (e.g., Ser / Thr) with an oxidizing agent to form an oxidized CD123 / IL-3Ra-binding agent having a N-terminal aldehyde group; (b) reacting the oxidized CD123 / IL-3Ra-binding agent having the N-terminal aldehyde group with a linker compound having an aldehyde reactive group to form a modified CD123 / IL-3Ra-binding agent having a linker bound thereto, followed by reacting the modified CD123 / IL-3Ra-binding agent with a cytotoxic agent. In certain embodiments, the immunoconjugates of the second embodiment can be prepared by a sixth method comprising the steps of: (a) oxidizing the CD123 / IL-3Ra-binding agent having a N-terminal 2- hydroxyethylamine moiety (e.g., Ser / Thr) with an oxidizing agent to form an oxidized CD123 / IL-3Ra-binding agent having a N-terminal aldehyde group; (b) contacting the oxidized CD123 / IL-3Ro-binding agent having the N-terminal aldehyde group with a cytotoxic agent followed by addition of a linker compound having an aldehyde reactive group. In one embodiment, for the first or fourth method described above, the cytotoxic agent having an aldehyde reactive group is represented by the following formula: Foy Py ORR Ze CR Rica o X 3 N 0. o HN=,, LD B ‘OMe MeO’ oO 0 (S1a’), Fo Py ORR Ze (CR Rees X © X XY Y \ N o o N= 0 0 = © O nd (Sla’l), RE w” Sel Jes lo fF = o o IN, o o (QIR) Ar w= 9 oT (SIb),or RS wees o Y X X, Y -A, o. o. nN Oo 0 (S1h*'1) = © oT (Sib, or a pharmaceutically acceptable salt thereof, wherein Jeg is represented by the following formula: NH, NH Fy f—un —0” 2 H . cor 3 sor ¢ NH Hy fn” # and the remaining variables are as described above in any one of 1% to 7% and 25* specific embodiments and any more specific embodiments described therein. In another embodiment, for the first or fourth method described above, the cytotoxic agent having an aldehyde reactive group is represented by the following formula: NH N Jes o Nt 00 ci oX OMe AALS rN (S4a’), rT __~ 0 SENNA ome oRNH 0 or a pharmaceutically acceptable salt thereof, wherein Jcs is as described above and the remaining variables are as described in the any one of he 19" to 25% specific embodiments and any more specific embodiments described therein. In one embodiment, for the second, third, fifth or sixth method described above, the compound is represented by the following formula: r 1 Bk: Raz Q (L'a) as lata pith Se bd haat i ats tabi al Fos Ros Jes =n Jp a | r Rf Raz Q | wherein Jp —SH, —-SSR¢, or ~SC(=O)R¢; R¢ is phenyl, nitrophenyl, dinitrophenyl, carboxynitrophenyl, pyridyl or nitropyridyl; RE is an alkyl; Jcs is as described above; the cytotoxic agent is represented by the following formula: HN—, Q, .SH Re, JR N YX N o o HN—, 4 ° . Q SH Re PR N YX X ; NY —7 =N OL. N=, N< XX N OMe wl 0 0 0 . RZ ww” SH Lg =N o° ° HN—, N 0 o . Caan Q Ri: 0 , or RX w SH Y, X X. -N OL. Nt! N oO Oo and the remaining variables are as described above in any one of the 8% to 13" and 25% specific embodiments and any more specific embodiments described therein. In another embodiment, for the second, third, fifth or sixth method described above, the linker compound is represented by formula (La) above; the cytotoxic compound is represented by the following formula: x 1 v \ Q Sr > ag 3 L R, Re MeO, MARL Ao Y No SENANA A ved HE N o and the remaining variables are as described in any one of the 14% to 18% and 25™ specific embodiments and any more specific embodiments described therein. In one embodiment, for the first or fourth methods described above, the cytotoxic agent is reacted with an imine-reactive reagent, such as NaHSO3, to form a modified cytotoxic agent before reacting with the oxidized CD123 / IL-3Ra-binding agent having the N- terminal aldehyde. In one embodiment, the modified cytotoxic agent is not purified before reacting with the oxidized CBA having the N-terminal aldehyde. Alternatively, the modified cytotoxic agent is purified before reacting with the oxidized CBA having the N-terminal aldehyde. In another embodiment, for the second or fifth method described above, the cytotoxic agent is reacted with an imine-reactive reagent, such as NaHSOs, to form a modified cytotoxic agent before reacting with the modified CD123 / IL-3Ro-binding agent having a linker bound thereto. In one embodiment, the modified cytotoxic agent is purified before reacting with the modified CD123 / IL-3Ra-binding agent having a linker bound thereto. Alternatively, the modified cytotoxic agent is not purified before reacting with the oxidized CD123 / IL-3Ra-binding agent having the N-terminal aldehyde. In yet another embodiment, for the third or sixth methods described above, the reaction of the oxidized CD123 / IL-3Ra-binding agent, the cytotoxic agent and the linker compound is carried out in the presence of an imine reactive reagent, such as NaHSOs. Any suitable oxidizing agent can be used in step (a) of the fourth, fifth or sixth method described above. In certain embodiments, the oxidizing agent is a periodate. More specifically, the oxidizing agent is sodium periodate. Excess molar equivalents of the oxidizing agent relative to the CD123 / IL-3Ra- binding agent can be used. In certain embodiments, about 2-100, 5-80, 10-50, 1-10 or 5-10 molar equivalents of the oxidizing agent can be used. In certain embodiments, about 10 or about 50 equivalents of the oxidizing agent can be used. When large amount of the oxidizing agent is used, short reaction time is used to avoid over-oxidation. For example, when 50 equivalents of the oxidizing agent is used, the oxidation reaction is carried out for about 5 to about 60 minutes. Alternatively, when 10 equivalents of the oxidizing agent is used, the reaction is carried out for about 30 minutes to about 24 hours. In one embodiment, 5-10 molar equivalents of the oxidizing agent is used and the oxidation reaction is carried out for about 5 to about 60 minutes (e.g., about 10 to about 30 minutes, about 20 to about 30 minutes). In certain embodiments, a catalyst is present in the reaction in the first, second or third method described above or in the reaction of step (b) in the fourth, fifth or sixth method described above. Any suitable catalyst in the art can be used. In one embodiment, the catalyst is an aniline or substituted aniline. Exemplary aniline catalyst include, but are not limited to, aniline, o-phenylenediamine, m-phenylenediamine, 3,5-diaminobenzoic acid, p-phenylenediamine, 2-methyl-p-phenylenediamine, N-methyl-p-phenylenediamine, o-aminophenol, m-aminophenol, p-aminophenol, p-methoxyaniline, 5-methoxy-anthranilic acid, o-aminobenzoid acid, and 4-aminophenethylalcohol. In one embodiment, the catalyst is 4-aminophenethylalcohol. In certain embodiments, the reaction of step (b) is carried out at pH about 5.0 to about 6.5. In certain embodiments, the reaction of step (b) is carried out at pH about 5.0. In certain embodiments, for the reaction in the first, second or third method described above or in the reaction of step (b) in the fourth, fifth or sixth method described above, the compound having an aldehyde reactive group (e.g., cytotoxic agent, or the linker compound described herein) is used in molar excess relative to the oxidized cell-binding agent (e.g., oxidized antibody or oxidized antigen binding portion). In certain embodiments, the ratio for the compound having an aldehyde reactive group to the oxidized cell-binding agent is between about 10:1 to about 1.1:1, between about 5:1 to about 2:1. In one embodiment, the ratio is about 4:1. In a third embodiment, the immunoconjugates of the present invention comprises a CD123 / IL-3Ra-binding agent (including antibody, antigen-binding fragment thereof, or polypeptide comprising the antibody or antigen-binding fragment thereof) described in the first aspect of the invention covalently linked to a cytotoxic agent described herein through the thiol group (-SH) of one or more cysteine residues located on the CD123-binding agent. In a 1* specific embodiment, the immunoconjugate of the third embodiment is represented by the following formula: cea{—cy! \, (C1), wherein: CBA is a CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject antibody or antigen-binding fragment thereof described herein above, or a subject polypeptide thereof described above), covalently linked to Cy©! through a cysteine residue; Weis lor2; Cy‘! is represented by the following formula: Rs oP _(CRaRo)m te} N YY Y, X _ N, o 5 HN— JOA N OMe MeO’ I 0 = ow 0 i (Cla); Roy Po ORR 0 0 YX X = OL. nt Im Ww a) o (Clal} (Clal); RS wee} 0 YX = 0. o. ip om wy 95) o oO (Clb), or RS we” eto} o Y, X Xx 7 \ =N, o. o. N— / N Oo o = © Oo 7 (Clbl) or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-C4)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SOsM, and Mis H" ora cation; Rsis -H or a (C1-Cs)alkyl; P is an amino acid residue or a peptide containing 2 to 20 amino acid residues; Ra and Re, for each occurrence, are independently -H, (Ci-Ca)alkyl, or a charged substituent or an ionizable group Q; W’ is -NR¢, R® is -(CH;-CH;-0)s-R¥; nis an integer from 2 to 6; Rk is -H or -Me; R® is a (C1-Ce)alkyl; and, Lc is represented by: s2 RM 2 Vii 2 Au Re YY st Ryo Ris wherein s1 is the site covalently linked to CBA, and s2 is the site covalently linked to the -C(=0)- group on Cy€!; wherein: Rus and Ray, for each occurrence, are independently -H or a (C;-Cj)alkyl; m” is an integer between 1 and 10; and R"is -H or a (C;-C3)alkyl. In a 2™ specific embodiment, for immunoconjugate of formula (C1), Cy®! is represented by formula (Cla) or (Clal); and the remaining variables are as described above in the 1% specific embodiment. In a 3* specific embodiment, for immunoconjugate of formula (C1), Cy! is represented by formula (C1b) or (C1b1); and the remaining variables are as described above in the 1% specific embodiment. In a 4" specific embodiment, for immunoconjugate of formula (C1), Cy! is represented by formula (Cla) or (Clal); Ra and Ry are both H; and Rs is H or Me; and the remaining variables are as described above in the 1% or 2™ specific embodiment. In a 5% specific embodiment, for immunoconjugate of formula (C1), P is a peptide containing 2 to 5 amino acid residues; and the remaining variables are as described above in the 1%, 27¢ or 4'h specific embodiment. In a more specific embodiment, P is selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu- Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N’-nitro-Arg, Phe-Phe-Lys, D-Phe- Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val- Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val- Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala- Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In another more specific embodiment, P is Gly- Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala. In a 6% specific embodiment, for immunoconjugates of formula (C1), Q is -SO:M; and the remaining variables are as describe above in the 1%, 2%, 4 or 5% specific embodiment or any more specific embodiments described therein. In a 7% specific embodiment, for immunoconjugates of formula (C1), R19 and Rao are both H; and m” is an integer from 1 to 6; and the remaining variables are as described above in the 1%, 24, 31 4th 5% or 6% specific embodiment or any more specific embodiments described therein. In a 8" specific embodiment, for immunoconjugates of formula (C1), -L-Lc- is represented by the following formula: H N OX dns d and the remaining variables are as described above in the 1%, 20d, 3, 4th 5th 6th or 7th gpecific embodiment or any more specific embodiments described therein. In a 9% specific embodiment, the immunoconjugate of the third embodiment is represented by the following formula: wu, 9 H a NA N oy TINY Yeon x 0 0 o NN Ao on N= N OMe MeO’ N Jw, LL Ho o 4 0 HN WSN SY spon % o My 0 Y N. 0. 0. Ner¥ © Com ne | 0 o << PYROS TE > / / we H 3 SecA MeO GAO Ay TT X ° he Yoh 0. 0. N < SL Co ” N OMe MeO N, is Ae sor XX! X | 3% <NODE 1 J we t o I MeO No SNS INN X oO x te y | \ Y =N o. o. Ney < JX CC > N OMe MeO’ N rs 0 J we or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or -SO3M. In a more specific embodiment, the double line == between N and C represents a double bond, X is absent and Y is —H. In another more specific embodiment, the double line == between N and C represents a single bond, X is —-H and Y is —SO:M. In a 10™ specific embodiment, the immunoconjugate of the third embodiment is represented by the following formula: caA-{—cy® he (C2), wherein: CBA is a CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject antibody or antigen-binding fragment thereof described herein above, or a subject polypeptide thereof described above), covalently linked to Cy? through a cysteine residue; Weis 1lor2; Cy“? is represented by the following formula: HN—, Q -S Re, Dro Se N YE N o ° HN—, oO oO (C2a), Q -S. Re. . Dr Sie Y, X X.Y = Oo 0 (C2al), xX RE ws He Sol -N, HN—, OL 0. ~~ N OMe Meo ~~ o ° o = (C2b), or RZ ws Le} Y X xX x A LL. N=, 0 Oo = © OT (C2bl), or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SO3M, and M is H" or a cation; Rx! is a (C)-Ce)alkyl; Reis -H or a (C,-Ce)alkyl; W’ is -NR¢’; R® is -(CH;-CH;-0)s-R¥; nis an integer from 2 to 6; R¥is -H or -Me; R*2 is a (C1-Ce)alkyl; Lc’ is represented by the following formula: sor Riz Riz NM 2s Py s1 Q RuRy © a oO Rh [o} Che I Apt 7 20 ~~ Nn de O Rp Ry Ryo Ris o wherein: sl is the site covalently linked to the CBA and s2 is the site covalently linked to -S- group on Cy®%; Z is -C(=0)-NRy-,0r -NRg-C(=0)-; Q is -H, a charged substituent, or an ionizable group; Ro, Rio, Rit, Riz, Rus, Rig, Rao, Rai and Raa, for each occurrence, are independently -H or a (Ci-C3)alkyl; q and r, for each occurrence, are independently an integer between 0 and 10; m and n are each independently an integer between 0 and 10; RP is -H or a (C1-C3)alkyl; and P’ is an amino acid residue or a peptide containing 2 to 20 amino acid residues. In a more specific embodiment, q and r are each independently an integer between 1 to 6, more specifically, an integer between 1 to 3. Even more specifically, Rio, R11, R12 and Riz are all H. In another more specific embodiment, m and n are each independently an integer between 1 and 6, more specifically, an integer between 1 to 3. Even more specifically, Rio, Rao, R21 and Ras are all H. In a 11% specific embodiment, for immunoconjugates of formula (C2), Cy“? is represented by formula (C2a) or (C2al); and the remaining variables are as described above in the 10% specific embodiment or any more specific embodiments described therein. In a 12 specific embodiment, for immunoconjugates of formula (C2), Cy? is represented by formula (C2b) or (C2b1); and the remaining variables are as described above in the 10" specific embodiment. In a 13% specific embodiment, for immunoconjugates of formula (C2), P’ is a peptide containing 2 to 5 amino acid residues; and the remaining variables are as described in the 10h, 11% or 12% specific embodiment or any more specific embodiments described therein. In a more specific embodiment, P’ is selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°- tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile- Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val- D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D- Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala. In another more specific embodiment, P’ is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D- Ala-Ala, or D-Ala-D-Ala. In a 14™ specific embodiment, for immunoconjugates of formula (C2), -Lc’- is represented by the following formula: p 0 st ¥ Mossy 2 0 H som 0 oO st rondo 0 H 2, or o} \ 9 o H Q H [o] ddd s2 oO Ina 15% specific embodiment, for immunoconjugates of (C2), R¢ is H or Me; R*! is - (CH2)p-(CR'R¥)-, and R*? is -(CHz)p-(CR'RY)-, wherein Rf and R¢ are each independently -H ora (C1-Cs)alkyl; and p is 0, 1, 2 or 3; and the remaining variables are as described above in the 10%, 11%, 12th, 13%, or 14" specific embodiment. More specifically, Rf and R€ are the same or different, and are selected from —H and -Me. In a 16™ specific embodiment, the immunoconjugate of the third embodiment is represented by the following formula: > 2 s SOM 4 Q mA See Sefncan 0 H Xx x e N 0. o. N: > ° ° Jw. Jones il i Wl Ng Rey x sajrcaa x X x d N. 0, 0, N: % {Xn =O ° 0° Jw, > gmt oncom STE § SITIO > Jw, 0 SN, Hon HN’ dhl N Sofncon v, X © / x J o N. O. 0. N: > © 0 we o o. s i 1 ~~ NoNINN N A A ° ae Se NNN ocr Phan lotn” # N. 0 0. N—, o sevpser oi N OMe MeO’ N & ry > Jw, o. o s. ] 1 AON Oy ~. No A > X SY N Sofa Xx x 0 pa Y. 1 Vy =N. 0. 0. Ney o 5 Ln nee | 0 0 Jw, $0 Te, 0 H 0. 0. s. AON Oy ~ AA A M idk 9) ® I N Scan A H 7 < =N o. o. N~, > : Conn wl | § d >" SOM > TT, 0 H AON NO S$. AAR A WC YX 5 N sfc Po Pnn de #7 Y o =N. 0. 0. Nef > N OMe MeO’ N | o 0 Zw, or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or -SOsM. In a more specific embodiment, the double line == between N and C represents a double bond, X is absent and Y is —H. In another specific embodiment, the double line == between N and C represents a single bond, X is —-H and Y is -SOsM. In a 17" specific embodiment, the immunoconjugate of the third embodiment is represented by the following formula: cantor), wherein: CBA is a CD123 / IL-3Ra-binding agent described in the first aspect of the invention (e.g. a subject antibody or antigen-binding fragment thereof described herein above, or a subject polypeptide thereof described above), covalently linked to Cy©? through a cysteine residue; Weis 1lor2; Cy©3 is represented by the following formula: (C3a) wherein: m’islor2; R, and Ry, are each independently -H or a (C;-C3)alkyl; Lc’ is represented by the following formula: Riz Ri 2s Ph dy s1 Q RuRy, © a oO Rh Q, Hd AD SOY Ry O Ry Ra Rao Ris © wherein: sl is the site covalently linked to the CBA and s2 is ...

Claims

THE CLAIMS DEFINING THE INVENTION ARE AS FOLLOWS:

1. An antibody or antigen-binding fragment thereof that: (a) binds an epitope within amino acids 101 to 346 of human CD123 / IL3-Ra antigen, and (b) inhibits IL3-dependent proliferation in antigen-positive TF-1 cells.

2. The antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment thereof binds an epitope within amino acids 101 to 204 of human CD123 antigen.

3. The antibody or antigen-binding fragment thereof of claim 1, wherein said antibody or antigen-binding fragment thereof binds an epitope within amino acids 205 to 346 of human CD123 antigen. 4, An antibody or antigen-binding fragment thereof that: (a) binds an epitope within amino acids 1 to 100 of human CD123 antigen, and (b) inhibits IL3-dependent proliferation in antigen-positive TF-1 cells, with an ICso value of 0.1 nM or less (e.g, 0.08 nM, 0.05 nM, 0.03 nM).

5. The antibody or antigen-binding fragment thereof of any of claims 1-4, wherein said antibody or antigen-binding fragment thereof inhibits the proliferation of leukemic stem cells or leukemic blast cells but not hematopoietic stem cells.

6. The antibody or antigen-binding fragment thereof of any of claims 1-5, wherein said antibody or antigen-binding fragment thereof binds to human CD123 antigen-positive cells with a dissociation constant (Kg) of 0.3 nM or lower.

7. The antibody or antigen-binding fragment thereof of claim 6, wherein said antibody or antigen-binding fragment thereof binds to human CD123 antigen-positive cells with a Ks of between 0.01 nM and 0.3 nM.

8. The antibody or antigen-binding fragment thereof of claim 7, wherein said antibody or antigen-binding fragment thereof binds to human CD123 antigen-positive cells with a Ku of between 0.01 nM and 0.2 nM.

9. The antibody or antigen-binding fragment thereof of claim 8, wherein said antibody or antigen-binding fragment thereof binds to human CD123 antigen-positive cells with a Ks of between 0.01 nM and 0.1 nM.

10. The antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the antibody or antigen-binding fragment thereof binds to cynomolgus monkey CD123.

11. The antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the antibody or antigen-binding fragment thereof binds to cynomolgus monkey CD123 with a Ks of between 0.05 and 0.3 nM.

12. The antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the antibody or antigen-binding fragment thereof binds to cynomolgus monkey CD123 with a Kg of between 0.05 and 0.2 nM.

13. The antibody or antigen-binding fragment thereof of any one of claims 1-9, wherein the antibody or antigen-binding fragment thereof binds to cynomolgus monkey CD123 with a Ks of between 0.05 and 0.1 nM.

14. The antibody or antigen-binding fragment thereof of any one of claims 1-13, wherein the antibody or antigen-binding fragment thereof binds both human and cynomolgus monkey CD123 with a substantially similar binding affinity.

15. The antibody or antigen-binding fragment thereof of claim 14, wherein the antibody or antigen-binding fragment thereof binds to human and cynomolgus monkey CD123 with a Ks of between 0.05 and 0.3 nM.

16. The antibody or antigen-binding fragment thereof of claim 14, wherein the antibody or antigen-binding fragment thereof binds to human and cynomolgus monkey CD123 with a Ku of between 0.05 and 0.2 nM.

17. The antibody or antigen-binding fragment thereof of claim 14, wherein the antibody or antigen-binding fragment thereof binds to human and cynomolgus monkey CD123 with a Ks of between 0.05 and 0.1 nM.

18. The antibody or antigen-binding fragment thereof of any one of claims 6-17, wherein Ka is measured by flow cytometry, surface plasmon resonance, or radioimmunoassay.

19. The antibody or antigen-binding fragment thereof of any of claims 1-18, wherein said antibody or antigen-binding fragment thereof inhibits at least 50% of IL3-dependent proliferation in antigen-positive TF-1 cells at a concentration of 0.5 nM or lower.

20. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) at least one heavy chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR 1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR is selected from the group consisting of: SEQ ID NOs: 1, 5, and 12, CDR2 is selected from the group consisting of: SEQ ID NOs: 2, 3, 6-10, 13, and 14, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 4, 11, and 15; and b) at least one light chain variable region or fragment thereof comprising three sequential complementarity-determining regions (CDR) CDR 1, CDR2, and CDR3, respectively, wherein, with the exception of 1, 2, or 3 conservative amino acid substitutions, CDR is selected from the group consisting of: SEQ ID NOs: 16, 19, 20, and 23, CDR2 is selected from the group consisting of: SEQ ID NOs: 17, 21, and 24, and, optionally, CDR3 is selected from the group consisting of: SEQ ID NOs: 18, 22, and 25.

21. The antibody or antigen-binding fragment thereof of claim 20, wherein said conservative amino acid substitutions comprise a substitution of at least one Lys in a CDR by an Arg.

22. The antibody or antigen-binding fragment thereof of claim 20 or 21, wherein said antibody is a CDR-grafted humanized antibody comprising mouse CDR regions, and wherein one or more (e.g., 1, 2, 3,4, 5, 6, 7, or 8) heavy chain and / or light chain framework region vernier zone residues of said antibody is of mouse origin.

23. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

41.

24. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 34; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

35.

25. The antibody or antigen-binding fragment thereof of claim 24, wherein Xaa, the second residue from the N-terminus of SEQ ID NO: 34, is Phe.

26. The antibody or antigen-binding fragment thereof of claim 24, wherein Xaa, the second residue from the N-terminus of SEQ ID NO: 34, is Val.

27. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40, except that the N-terminal residue is Ser; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

41.

28. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 39 or 40; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41, except that the N-terminal residue is Ser.

29. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the N-terminal residue is Ser, and except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

41.

30. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO: 41, except that the N-terminal residue is Ser.

31. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 38; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

35.

32. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain variable region having the amino acid sequence set forth in SEQ ID NO: 34; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

37.

33. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 56; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

35.

34. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

37.

35. The antibody or antigen-binding fragment thereof of any one of claims 31-34, wherein Xaa, the second residue from the N-terminus of SEQ ID NOS: 38, 34, 56, and 54, is Phe.

36. The antibody or antigen-binding fragment thereof of any one of claims 31-34, wherein Xaa, the second residue from the N-terminus of SEQ ID NOS: 38, 34, 56, and 54, is Val.

37. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 59 or 60, except that the residue corresponding to the 5% to the last residue of SEQ ID NO: 54 is Cys; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

41.

38. The antibody or antigen-binding fragment thereof of any of claims 1-19, comprising: a) an immunoglobulin heavy chain region having the amino acid sequence set forth in SEQ ID NO: 54; and b) an immunoglobulin light chain variable region having the amino acid sequence set forth in SEQ ID NO:

35. 39, The antibody or antigen-binding fragment thereof of claim 38, 33, or 34, wherein Xaa, the second residue from the N-terminus of SEQ ID NO: 54 or 56, is Phe.

40. The antibody or antigen-binding fragment thereof of claim 38, 33, or 34, wherein Xaa, the second residue from the N-terminus of SEQ ID NO: 54 or 56, is Val.

41. The antibody or antigen-binding fragment thereof of any one of claims 1-3 and 5-20, comprising: a) an immunoglobulin heavy chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 1, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 2 or 3, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 4; and b) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 16, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 17, and a CDR3 having an amino acid sequence set forth in SEQ ID NO:

18.

42. The antibody or antigen-binding fragment thereof of any one of claims 1-3 and 5-20, comprising: a) an immunoglobulin heavy chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 5, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 6, 7, 8, 9, or 10, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 11; and b) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 19 or 20, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 21, and a CDR3 having an amino acid sequence set forth in SEQ ID NO:

22.

43. The antibody or antigen-binding fragment thereof of any one of claims 4-20, comprising: a) an immunoglobulin heavy chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 12, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 13 or 14, and a CDR3 having an amino acid sequence set forth in SEQ ID NO: 15; and b) an immunoglobulin light chain variable region comprising a CDR1 having an amino acid sequence set forth in SEQ ID NO: 23, a CDR2 having an amino acid sequence set forth in SEQ ID NO: 24, and a CDR3 having an amino acid sequence set forth in SEQ ID NO:

25. 44, The antibody or antigen-binding fragment thereof of any of claims 1-43, comprising: a) a Vu sequence at least 95% identical to a reference Vu sequence selected from the group consisting of: SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably 26, 28, 30, 32, 34, and 38); and / or, b) a Vi sequence at least 95% identical to a reference Vi sequence selected from the group consisting of: SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (preferably 27, 29, 31, 35, and 37).

45. The antibody or antigen-binding fragment thereof of claim 44, wherein the Vg sequence is at least 99% identical to one of SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably 26, 28, 30, 32, 34, and 38), and / or wherein the V1 sequence is at least 99% identical to one of SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (preferably 27,29, 31, 35, and 37).

46. The antibody or antigen-binding fragment thereof of claim 45, comprising: a) a Vy sequence selected from the group consisting of SEQ ID NOs: 26, 28, 30, 32, 34, 38, 39, and 40 (preferably 26, 28, 30, 32, 34, and 38); and / or, b) a Vi sequence selected from the group consisting of SEQ ID NOs: 27, 29, 31, 33, 35, 37, and 41 (preferably 27, 29, 31, 35, and 37).

47. The antibody or antigen-binding fragment thereof of claim 46, comprising a Vu sequence of SEQ ID NO: 26 and a Vi sequence of SEQ ID NO:

27.

48. The antibody or antigen-binding fragment thereof of claim 46, comprising a Vu sequence of SEQ ID NO: 28 and a Vi sequence of SEQ ID NO:

29.

49. The antibody or antigen-binding fragment thereof of claim 46, comprising a Vu sequence of SEQ ID NO: 30 and a Vi sequence of SEQ ID NO:

31.

50. The antibody or antigen-binding fragment thereof of claim 46, comprising a Va sequence of SEQ ID NO: 34 and a Vi sequence of SEQ ID NO:

35.

51. The antibody or antigen-binding fragment thereof of any one of claims 1-49, wherein said antibody is a murine, non-human mammal, chimeric, humanized, or human antibody.

52. The antibody or antigen-binding fragment thereof of claim 51, wherein said humanized antibody is a CDR-grafted antibody or resurfaced antibody.

53. The antibody or antigen-binding fragment thereof of any one of claims 1-52, wherein said antibody is a full-length antibody.

54. The antibody or antigen-binding fragment thereof of any one of claims 1-52, wherein said antigen-binding fragment thereof is an Fab, Fab’, F(ab’), Fg, single chain Fv or scFv, disulfide linked Fy, V-NAR domain, IgNar, intrabody, IgGACH>, minibody, F(ab’), tetrabody, triabody, diabody, single-domain antibody, DVD-Ig, Fcab, mAb, (scFv), or scFv-Fec.

55. A polypeptide comprising the Vu and V1 sequences of any of claims 1-54.

56. The polypeptide of claim 55, which is a fusion with a protein that is not a pseudomonas toxin.

57. A cell producing the antibody or antigen-binding fragment thereof of any one of claims 1-54, or the polypeptide of claim 55 or 56.

58. A method of producing the antibody or antigen-binding fragment thereof of any one of claims 1-54, or the polypeptide of claim 55 or 56, comprising: (a) culturing the cell of claim 57; and, (b) isolating said antibody, antigen-binding fragment thereof, or polypeptide from said cultured cell.

59. The method of claim 58, wherein said cell is a eukaryotic cell.

60. An immunoconjugate having the following formula: cao), wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 23-26, or the polypeptide thereof of claim 55 or 56, that is covalently linked through a lysine residue to Cy; ‘Wi is an integer from 1 to 20; and Cyl! is represented by the following formula: > Wa HN—, N o.

0. iS o Oo - hat lo} o oT , or wi” Meg J © Wil QO) — 0 0 % eePery, I I or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1- Cas)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SOsM; W’ is -NR€, R® is -(CH,-CH-0)s-R¥; nis an integer from 2 to 6; Ris -H or -Me; R* is a (C1-Ce)alkyl; L’ is represented by the following formula: -NR;s-P-C(=0)-(CRaRp)u-C(=0)- (BI); or -NR;s-P-C(=0)-(CRuRp)m-S-Z5!- (B37); Rs is -H or a (C1-Ca)alkyl; P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues; Ra and Ry, for each occurrence, are each independently -H, (Ci- Cs)alkyl, or a charged substituent or an ionizable group Q; m is an integer from 1 to 6; and Z:! is selected from any one of the following formulas: mcr Ae . 0 bl); rr (bl); o (b2); 0 (b3); o gong 3 OM Jens 5 %, AY AAA (bd): (b4); 0 (b5), Ford hrp he 0 [ (b6), 0 (Saas £ ML Ts Tn > (b7); o (b8); o ° (b9); and “J 7 0 A 0 ( SOM AAA 0 ¢ (b10), wherein: q is an integer from 1 to 5; and M is H™ or a cation.

61. The immunoconjugate of claim 60, wherein Ra and Rs are both H; and Rs is H or Me.

62. The immunoconjugate of claim 60 or 61, wherein P is a peptide containing 2 to 5 amino acid residues.

63. The immunoconjugate of any one of claims 60-62, wherein P is selected from Gly- Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe- Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu- Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D- Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg- D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala.

64. The immunoconjugate of claim 63, wherein P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala- D-Ala, D-Ala-Ala, or D-Ala-D-Ala.

65. The immunoconjugate of any one of claims 60-64, wherein Q is -SO3M.

66. The immunoconjugate of claim 60, wherein the immunoconjugate is represented by the following formula: 2 on 2H ) aA FT a tp daa Y N, 0.

0. N=f > N OMe MeO N, | o o i J wi Idiom be CBA Aandi l Gf “Api wm > La t= Jw Y§ i adoro fn hen Pow tooo hey > Od & Jw Ks © TN Ja a Afi 1 rr Ds by > Zw lal = < NAO ae Moan > 2 ond fos ~ NS 0 0 H 3 < NA © CNL > CL OMe wd | 0 g 0 ow, ~N o oy 0 SAA dca H H 0 o H Xy N 0.

0. Ney > oe * ~ or CC 0 o 5 a 9 Q SOM fe H N_ A s. NCBA wy YK ~ wiry - X < N Oa ne’ ” mM (Cn As 0 0 J Be zr = Jw ou 0 fi NA s Neon CBA wy rx NY - X Y < R Ds Ne > OO N OMe MeO N, |b 0 J Jw, a 4 0 fo N= s NCBA op YK ~NY H Oxy © N. fo) 0. N= / > (Com nA is 0 3 Jw IA 1 io fica ; s oN SK NN " AE 0 N fo) 0. ) > N OMe MeO N o 0 J Jw, Q 0 SOM 4 H SH JN : s Ne CBA HN” YK Ne NY - 0 x o H ry N.

0.

0. N= / > Is 0 Jw o 4 0 fa AS SRN YT 524 f Ls Wf ” Gf wl Os 0 J, Lad ir N_ s Neon CBA HN YK ~NY H C0 xy © N. fo) 0. N= / > (Com nA is 0 3 Jw 9 0 SOM fe H . JN : s Netan CBA as SK NN " - 0 x 0 N fo) 0. ) > N OMe MeO N o 0 J Jw, oa L,Y o SOM An No 2 s New CBA oN YK ~~. AN WOYTN 0 IN xX . > Joo 3 Hy a 8 0.

0. Ney Cn A Is 0 Jw a 4, XY o H NA S Netw CBA wy NK ~ NN A - YH ¥ 0 N\ xX . > i o Bo / \ N 0. o. Ne’ (Cn nL J % 0 J, > 9 y Y 7 fo NA s Net CBA op NO ~NY H Oxy © N. fo) 0. N= / > is 0 Jw < ~ EE CN / - > SAS 70% fon ~ S. HN NX NN “ - 0 x v 0 < N.

0.

0. N= / > Cm A | oO o Nn Jw sor O.

0. f CBA Og Oy ronson ~Y * & O. R < NY TF N OMe MeO N | 0 0 wy or a pharmaceutically acceptable salt thereof, wherein Wi is an integer from 1 to 10; the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when itis a single bond, X is -H, and Y is -OH or -SO3M.

67. An immunoconjugate having the formula: CBA Aor), wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 23-26, or the polypeptide thereof of claim 55 or 36, that is covalently linked to Cy? through a lysine residue; W. is an integer from 1 to 20; and Cy? is represented by the following formula: Q, -S. "IN oer YX N, 0. 0 HN—, 0 oO . Oo o aor we any Y, oS am > I J OMe MeO ® Bes or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (Ci- Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SO:M; R*! and R® are independently (C1-Ce)alkyl; Reis -H or a (C,-Ce)alkyl; W’ is -NR€', R¢' is -(CH2-CH2-0)a-R¥; nis an integer from 2 to 6; R¥ is -H or -Me; Z*! is selected from any one of the following formulas: ar o A caf 7 Lv NN oA A ~ (bh?) SY bl); C (bl); o (b2); 0 (b3); SoM ii 5 %, ANA AAA (b4): (b4); 0 (b5), 9 ig 1 I~ Sehr (b6), gp 0 Fu 0 ~ A gh gp (b7); o (b8); o ° (b9); and J 2 0 A 0 ( SOM SOM Ju AAA | (b10), wherein: q is an integer from 1 to 5; and M is -H™ or a cation.

68. The immunoconjugate of claim 67, wherein R® is H or Me; R*! and R* are independently -(CH2),-(CR'R®)-, wherein Rf and R¢ are each independently -H or a (Ci1-Cq)alkyl; and pis 0, 1, 2 or 3.

69. The immunoconjugate of claim 68, wherein Rand RE are the same or different, and are selected from -H and -Me.

70. The immunoconjugate of claim 67, wherein the immunoconjugate is represented by the following formula: > dorian ies tn Sande SE Ap > \ SF adorn Len f Oa SN SE AL, } Jw PN I a Os Wo Jol XL a Jw > [+] SOM, ada AA on mM | &- o MeO J O nN Jw, H Ono Ss ed CBA X Q y | H N 0. O. N > | $ d wo . sor or of Nee CBA ONO NENA AN Yo Se ph i \ TTT Yt ¥ \ Qe Ri > Go = 0 or a pharmaceutically acceptable salt thereof, wherein Wy is an integer from 1 to 10; the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when it is a single bond, X is -H and Y is -OH or -SO:M.

71. The immunoconjugate of any one of claims 60-70, wherein the double line == between N and C represents a double bond, X is absent and Y is -H.

72. The immunoconjugate of any one of claims 60-70, wherein the double line == between N and C represents a single bond, X is -H, and Y is -SO:M.

73. The immunoconjugate of claim 72, wherein M is H", Na” or K™.

74. An immunoconjugate having the formula: CBA 4c), wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 23-26, or the polypeptide of claim 55 or 56, which is covalently linked to Cy-® through a Lys residue; Woy is an integer from 1 to 20; CyL is represented by the following formula: o WN s ; act av 9 5 Ry Re MeO, N . SEAN 1 = 4 Med’ HO N ° The m’is1or2; Ri; and Ry, are each independently H or a (C1-Cs)alkyl; and Z%! is selected from any one of the following formulas: er 0 A crap Ls vc NN ¥ oA A ~ (bh?) SY bl); or (bl); o (b2); 0 (b3); SoM AAA o ANA i" o Brg 0 { (b6), le) (Saas 1 ThA NTNNA & “A 7): ~ 7 sr wid Q © boy, AAR NY wherein: q is an integer from 1 to 5; and M is H or a cation.

75. The immunoconjugate of claim 74, wherein m’ is 1, and R; and R> are both H.

76. The immunoconjugate of claim 74, wherein m’ is 2, and R; and R; are both Me.

77. The immunoconjugate of claim 74, wherein the immunoconjugate is represented by the following formula: 0 hY _S 2 § NCBA . 3 o SOM 89 eo, N . ~— LX ~N"So med HO N J L aw COWL Cr, ~~ 1 med HE NO Ju Lor Q 0 aq qo” H H N i o YOY “NY A oe 0 a3 XA ® < eo iy > LA — Med’ nd N © rd Wi eT YY oy Nononn CBA Sy i ° “ S. Tl CO - & ° wed HO yo Tow or a pharmaceutically acceptable salt thereof, wherein Wr is an integer from 1 to 10.

78. The immunoconjugate of claim 77, wherein M is H", Na* or K*.

79. An immunoconjugate having the following formula: —or) 2 Jos ceadr wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of claim 55 or 56, covalently linked to the Jes’ group, Wsis 1,2, 3, ord; Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of claim 55 or 56, and an aldehyde reactive group on Cy*!, and is represented by the following formula: 0 Hy, H 0 s1 Fee, s1 F-y, s1 Fey 2, Hy H sic “py " ie, KH Yim, RK sift staf H Ne=N N. Pode Ee 1 jor wherein s1 is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy*!; Cy! is represented by the following formula: Foy Py OR — Za CR— Jo 0 xX ab 0 Yo .l N 0 o. HN—=, o o , Or oD, SO =O or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SO3M, and M is H" or a cation; Rs is -H or a (C;-C3)alkyl; P is an amino acid residue or a peptide containing 2 to 20 amino acid residues; Zs is absent, -C(=0)-NRy-, or -NRy-C(=0)-; Ry is -H or a (C;-Cs)alkyl; Ra and Ry, for each occurrence, are independently -H, (C1-Cs)alkyl, or a charged substituent or an ionizable group Q; rand r’ are independently an integer from 1 to 6; W’ is -NR¢, R® is -(CH,-CH-0)s-R¥; n is an integer from 2 to 6; Ris -H or -Me; R* is a (C)-Cs)alkyl; L is -NRg-(CRaRb) or absent; and 1 is an integer from 0 to 6.

80. The immunoconjugate of claim 79, wherein Ra and Rs are both H, and Rs and Rg are both H or Me.

81. The immunoconjugate of claim 79 or 80, wherein P is a peptide containing 2 to 5 amino acid residues.

82. The immunoconjugate of any one of claims 79-81, wherein P is selected from the group consisting of: Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys- Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°- nitro-Arg, Phe-Phe-Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D- Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala.

83. The immunoconjugate of claim 82, wherein P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala- D-Ala, D-Ala-Ala, or D-Ala-D-Ala.

84. The immunoconjugate of any one of claims 79-83, wherein Q is -SOsM.

85. The immunoconjugate of claim 80, which is represented by the following formula: 0-4 X 9 H Hoo: i Jy N. WSS ~N SN=CmhCBA mA TH I ee g X N Do hy > Cn wt o o y 2 wg ; 0-4 > 0 9 H H AA A Aaa N HN N N—CamrCBA TH ° 04 H 7 Xx H NY Roo oN > Cn neg: 0 o J] ws > App 4 H ge oy ig GH wt | 4 < ws ; 0 Hs 2 H ” . A WINS NG NV TH 0° nH X H NAO NL > Cm wa 0 o 5 < ws y > 9 H J HAI AA, HN =C CBA of 0 gt x N o o Ney’ > Ce WH ry , < ws oO uo. Q H N N Hy AS N—CdcBA PY 4 o HH ed Vv Xx H id - < —No ALO Je IR ola NY > 1 ' oo H X i 0.

0. Neg¥ Com WH S 3 2) ws Og Oe i q t NY ~~ SN=C JwCBA A [I oa b XxX < R a OY Job BO a AS > Eo w- | a ° x, 0-4 < i 0.

0. N= / AL fo N OMe MeO’ N ys J ws H H H 0 0 » N A No NSN ~~ SNe CBA P J % 0-4 Hy < _H ) LY NN. 0 Js 0 ~~ N= / > - 0 x . 0-4 | < y o 0 N= / ~ / ™ N OMe MeO’ N Ys J NF xX Sow s R o 0.

0. NTN SN= AION SNS N gms H he 0 xX < RR CY Jo IL TO. A > LCC 0 i IY ( OMe wl ey ws Xx < RH 4 tls A > H 0 OO NaS On— Ls 0 NTN N &] CBA o X H | < N Os N=" ” ~ 7 N OMe MeO N Is 3 9] ws H 0.

0. N Oa SO i 0 Nad N: CH mnfon-CBA oO > 20 3. Sia 0 x TY R Ola N= / 5 rl / ™ N OMe MeO N ot J J Ws sor H N.

0.

0. AINE SN— BA ~N Chg z © x H | TY < NN ALESAO ANS = ie 3 J H TY % NO oss» LIX Co N OMe MeO N TY J I Ws or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or - SOM.

86. An immunoconjugate having the following formula: $2 ceadr Jog —Cy ). wherein: CBA is the antibody or antigen-binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of any claim 55 or 56, covalently linked to the Jes’ group, Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of claim 55 or 56, and an aldehyde reactive group on Cy*2, and is represented by the following formula: Ho H i il st Fea fe, s1§—c Hy fo, st Feta " Hy sor Roe 3 bad ’ tad H, H ste sig H C —N Ne=N Ne—N s1 “Ni 2 7 ~o—} ” a ~o— @ 4 sor wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy*%; Cy* is represented by the following formula: pt Sf Oe OO i J te LL sor RX? wo s-L—$ Y, IC pod OO I J ove Ls 2D or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (Ci- Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, and Y is -OH or -SO:M; Mis H' or a cation; R*! is a (C1-Ce)alkyl; Reis -H or a (C-Cs)alkyl; W’ is -NR¢, R® is -(CH2-CH-O)s-R¥; n is an integer from 2 to 6; R¥ is -H or -Me; R* ji sa (C 1-Cs)alk yl; L, is represented by the following formula: Raz Q Ras Ry, s4 $3 Zp 2 a r q1 | Raz Q Rat wherein: s3 is the site covalently linked to the group Jes’; s4 is the site covalently linked to the -S- group on Cy*2; Za is absent, -C(=0)-NRy-, or -NRy-C(=0)-; Ro is -H or a (C;-C3)alkyl; Q is H, a charged substituent or an ionizable group; Rai, Raz, Ras, Rag, for each occurrence, are independently H or (Ci-Ca)alkyl; and ql and rl are each independently an integer from 0 to 10, provided that q1 and rl are not both 0.

87. The immunoconjugate of claim 86, wherein -L;- is represented by the following formula: , $3 , DN coM s Ans “ wold Ss A Ns] oi, vw R vw R ne wt EAM AA st nN wai 0 0 sor 0 or a pharmaceutically acceptable salt thereof, wherein R is H or -SOsM.

88. The immunoconjugate of claim 86 or 87, wherein R° is H or Me; and R*! is -(CHa)p- (CR'R®)-, and R* is -(CH2)p-(CR'R®)-, wherein Rf and RS are each independently -H or a (C1-Cs)alkyl; and pis 0, 1, 2 or 3.

89. The immunoconjugate of claim 88, wherein Rf and Re are the same or different, and are selected from -H and -Me.

90. The immunoconjugate of claim 86, which is represented by the following formula: 0 g H S. AA N=Clcea I H oy > N.

0.

0. N: Sie "J o Oo J ws. J ws. o 9 H 4 N-C¢cea MINAS H x H y > u OL. N a nee 0 0 J we u 0 xy > SM ° 0 / J ows 1 1 s 1 mA ~ YY “ito H Xx ° > N 0.

0. N={ 0 0 “we Av YI Wg 9 H s. No __H2 HN ~~ Y N—C'frcen z 0 H | Y > N 0 0. N OMe MeO’ , | oO 0 ’ oo oo ows. 0 SOM yy N. H ASN AN “v=o o X H TF N.

0. N: > (SK nee o > Wg 0 SOM H N HN SAY SN—c~rcBa Ss Tr HR H Xx N 0 0 N=( > Ks TR 0 0 NJ © oo J J Ws 1 i i s. mA Se NY VY ae Xx 0 k Os he > XX OC 5 o 0 i. a do ~ ad J Ws. 1 { R S\. SN=C nnhnCBA aD NY ~~ i, H Ty FN 0.

0. N: > XX OC 3 o o >. 7 Wg o SOM § i s SN==C CBA mA X 0-4 H | ¥ N.

0.

0. N; > a o o J J “Wg o SOM pH iN N I OD ¢ “NY “Nc CBA 04 H, Yao 0 H N 0, 0. N={ > 3 o oO a 7 ws Q H s. Omg hcan mA NN NN c X o H 1 N 0.

0. N > 0 o | ga YN Jug o H RNY Ng o tng N. 0, 0. N: > { XX OC 0 o | ov © Na I Jus SOM yy 0. sda AA goes X o OL n y > o o 1 oO ov NA I Jus SOM N 0. NN NN ge H Hy X o H 1 N 0.

0. N > 3 o o 1 SE vo IF Jus Aves 8 H HN 7 Ng pot -can Ne f 0.

0. Nel > SIE 0 | we we s RN i £d-con ~ N—C HN % YY ~~ No >. % SOM 0 i o o. Ne! > Sr TRS 0 o Fi No °o Jus ONO AS pon ® Hi x o “en gel Re, > So wl 0 0 Ws s y ANNO “xX STN 3 a xX A 8 2| Kad 1 Z\ 2 ~~ X H Ys N 0.

0. N—, A» * on NS C » 0 0 Ws EY] 0.

0. Ss R PN SNC ~~ SN=¢ CBA x H ! \ OL N ° 0. ~— < or > N OMe MeO N o o JF Wg SOM $s AANA 0.

0. Oo Oy ~~. NN - ~~ o Ng] CBA o NA i < © O ™, > N OMe MeO N. o o 7 Wg fo) O. S. NN N=C CBA AION STN ~~ oo” et X | H < en Sel N—, r ™ N OMe MeO’ N | [] oO Ws 0. 0 S Rc CBA Ao NX ~Ne NTN gf X | H < en J, Ns, a ™ N OMe MeO’ N oY : 1 | COM < EY Ws R N——{ CBA AON ONIN TN No = =g 1 | X com © | H 2 < YN oa N-, > A A 0 0 Wg i CoM < Oo ON S R Rc CBA o WC ~ SN NN a Xx | com © < Yen Os R=, ’ r JX OMe MeO’ " o o H X 1 i Ws 0 0.

0. S. N—C CBA Oo Oy ~— AU N— TT N H « x s N Yo H > xr 0.

0. N—, ™ Cem A, o 0 We CZ A NF aa Ws 9 H O.

0. S. N—-°C: CBA AON Oy ~~. AU ~ z . Ks N 2 Y. | H N 0.

0. N—, N—( : ‘OMe MeO’ : rN 0 o ” Wg | 2 x © ws or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H; and when it is a single bond, X is -H; and Y is -OH or - SOsM.

91. The immunoconjugate of any one of claims 70-90, wherein the double line == between N and C represents a double bond, X is absent and Y is -H.

92. The immunoconjugate of any one of claims 79-90, wherein the double line == between N and C represents a single bond, X is -H and Y is -SOsM.

93. The immunoconjugate of claim 92, wherein M is H", Na* or K*.

94. An immunoconjugate having the following formula: —or) avr Jes! CB wherein: CBA is the antibody or antigen-binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of claim 55 or 56, covalently linked to the Jcs’ group; Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of claim 55 or 56, and an aldehyde reactive group on Cy*3, and is represented by the following formula: o Ho H o —~ s1 Fey) sl Fay, s1 Fey 2, H, sor H H st stl H stf—C-NQ, Ne=Na, Neh, N i 2, b —1 2 5 Hz °— 52 wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy*3; Cy* is represented by the following formula: - 1d ICPILOLIIILU DY LIL 1ULOW LE 101d. o WN s + ~ Hie L—i ay 3 © KR MeO MARL . © No ~~ 1 Ao SENN A ved HE N © wherein: m’is 1 or2; Ri and Ry, are each independently H or a (C1-C3)alkyl; L, is represented by the following formula: Raz Q Ras Ry, s4 $3 Zp 2 a r q1 | Raz Q Rat wherein: s3 is the site covalently linked to the group Jes’; s4 is the site covalently linked to the -S- group on Cy%3; Za is absent, -C(=0)-NRy-, or -NRy-C(=0)-; Ro is -H or a (C;-C3)alkyl; Q is H, a charged substituent or an ionizable group; Rai, Raz, Ras, Rag, for each occurrence, are independently H or a (C1-Ca)alkyl; and ql and rl are each independently an integer from 0 to 10, provided that q1 and rl are not both 0.

95. The immunoconjugate of claim 94, wherein m’ is 1 and R; and R; are both H.

96. The immunoconjugate of claim 94, wherein m’ is 2 and R; and R; are both Me.

97. The immunoconjugate of any one of claims 94-96, wherein -L;- is represented by the following formula: , $3 YO CoM : Ano , vod 1s) ? os s4 vw R Ss N S iy 1 2 s4 oF ‘On ’ S . Fa ors yo 0 sor o or a pharmaceutically acceptable salt thereof, wherein R is H or -SOsM and M is H* or a cation..

98. The immunoconjugate of claim 94, wherein the immunoconjugate is represented by the following formula: conn, Foi Ang ws, osafor, A, PN s Ay | N © J Ws. 0 CBA: —N, += WO Se { 0M 3 Hoar =U;M O J We Ss. gy 0 tod NSA | OM ) CL SUM : - 4 Ws. contin t ~Ho I J Ws / \ Jug, u 0 opag—g—H, ANN ES on I J Wg, Bh 2, Jug. H 0 rion oe 2 J O CoH / N\ Jug. 0 H H CBA——C—N, N, TN NN O,H J Wa QO $ COH / N\ dum, or a pharmaceutically acceptable salt thereof; wherein DM is represented by following formula: Me, \ SN 0 Nt 0 A Cl \ V MeO, AARL, ’ CN Y Ao SESE ny ved Hd N o 99. An immunoconjugate having the following formula: 4 car ics — Cy \. wherein: CBA is the antibody or antigen-binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of any claim 66 or 56, covalently linked to the Jes’ group, Jes’ is a moiety formed by reacting an aldehyde group derived from oxidation of a 2-hydroxyethylamine moiety on an N-terminal of said antibody or antigen- binding fragment thereof of any one of claims 27-36, or the polypeptide thereof of claim 55 or 56, and an aldehyde reactive group on Cy** and is represented by the following formula: = i + =N. c—N I s1 C=N_, i 2 s1 = , s1 ~N 2, A H, sor Hy H si sil H C =N Ne=N —N s1 = “Ni 52, $= ~o—} 2 Se “o— s2 wherein sl is the site covalently linked to the CBA; and s2 is the site covalently linked to Cy*; Cy™ is represented by the following formula: 0 NIN oo cl > OMe, MAAL rN rT __~ 0 SPAN As ome oRNH 0 L,’ is represented by the following formula: s3 2, Z s4 “ wh Re! Ry © . sor E Z s4 2 02, 2 $3 Zs Ene —N SY i Rs Ri oo Ros Rua wherein: s3 is the site covalently linked to the group Jes’ group; s4 is the site covalently linked to -NMe- group on Cy*; Zy) and Zs are both absent, or one of Z) and Zs: is absent and the other is - CH,-0- or -O-CH;-; Zyy” and Zy2' are each independently absent, -CHz-O-, -O-CH»-, -NRg-C(=0)- CHa-, or -CH2-C(=0)-NRo-; Ry is H or (C;-C3)alkyl; nl and m1 are each independently an integer from 1 to 6; one of Ei and Ez is -C(=0)-, and the other is -NRy-; or one of E; and Ez is - C(=0)- or -NRy-, and the other is absent; P is an amino acid residue or a peptide containing between 2 to 20 amino acid residues; and Ro1, Roz, Rus, Res, Ros and Res, for each occurrence, are each independently H ora (C;-Cs)alkyl.

100. The immunoconjugate of claim 99, wherein Roi, Rb2, Res, Ros, Ros, and Res are all H.

101. The immunoconjugate of claim 100, wherein Rg is H.

102. The immunoconjugate of any one of claims 99-101, wherein Zs,’ and Zs,’ are both absent; or Zs)’ is -CH2-O-; and Zv,’ is absent; or Zy;’ is -CH2-C(=0)-NRy-; and Zs?’ is -O-CHs- or absent.

103. The immunoconjugate of any one of claims 99-102, wherein P is a peptide containing 2 to 5 amino acid residues.

104. The immunoconjugate of any one of claims 99-103, wherein P is selected from Gly- Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N%-nitro-Arg, Phe-Phe- Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu- Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D- Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg- D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala.

105. The immunoconjugate of claim 104, wherein P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, and D-Ala-D-Ala.

106. The immunoconjugate of claim 99, wherein immunoconjugate is represented by the following formula: o o O, cangun, A NS. S ws, o o oeafor RN AoA, f i] 3 dws, 3 0 coat ] J ws Oo cong ton Tt 5 ws, : H H foc DM EE | Jw DM | o A y My HN AN N cea ws, 3 2 o a ~ Ju, ou] 0 H rr 2 My f Ny ~ A BACH, y cl Jus, OM | Qn N ad aA ~ Nn 1 N cBA—G— - oY ws, DM Ts Eo | H H Nw Ty Y A Jue, fu DM 1 i OY ¢ R AN Ny | Soy J we ; i DM R IR Ao OY ‘ H No~y TN I CN. N I cosa; ws, tJ A CBAG=N ~NT i | 4 Ws. cBAF—G—N N N Fy N om { J ws, CBASE=N. x l ws, cag ~™ | ws, or a pharmaceutically acceptable salt thereof, wherein DM is represented by the following structural formula: Me, \ No \ 0 Nt " o~ cl \ v MeO, MARL, rN 1 I I «A yo MeO HO H 107. An immunoconjugate represented by the following formula: cea{—cy®! , wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 37,29, 30, 38, 33, and 34, or the polypeptide thereof of claim 55 or 56, covalently linked to Cy©! through a cysteine residue; Wcislor2; Cy! is represented by the following formula: xX Rey PN (CRaRo)m te} N YT YX - N. o o HN—, oC » OMe MeO I 0 . 0 \——— sor wee X i J) - ny or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (C1-Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is -OH or -SO3M, and M is H* or a cation; Rsis -H or a (C1-Cs)alkyl; P is an amino acid residue or a peptide containing 2 to 20 amino acid residues; Ra and Ry, for each occurrence, are independently -H, (C1-Cs)alkyl, or a charged substituent or an ionizable group Q; W’ is -NR¢, R® is -(CH2-CH>-O)-R%; nis an integer from 2 to 6; Rk is -H or -Me; R*¥ is a (C1-Ce)alkyl; and, RM RB hy Ne HY R2o Rig © Lc is represented by Raz Te 7 , sl is the site covalently linked to CBA, and s2 is the site covalently linked to the -C(=0)- group on Cy‘; wherein: Rig and Rao, for each occurrence, are independently -H or a (C;-Cs)alkyl; m” is an integer between 1 and 10; and R" is -H or a (C,-Cs)alkyl.

108. The immunoconjugate of claim 107, wherein Ra and Ry are both H; and Rs is H or Me.

109. The immunoconjugate of claim 107 or 108, wherein P is a peptide containing 2 to 5 amino acid residues.

110. The immunoconjugate of any one of claims 107-109, wherein P is selected from Gly- Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N°-tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe- Lys, D-Phe-Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu- Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D- Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg- D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala.

111. The immunoconjugate of claim 110, wherein P is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala.

112. The immunoconjugate of any one of claims 107-111, wherein Q is -SOsM.

113. The immunoconjugate of any one of claims 107-112, wherein Rg and Ryo are both H; and m” is an integer from 1 to 6.

114. The immunoconjugate of claim 113, wherein -Lc- is represented by the following formula: H N 2 ds oO 115. The immunoconjugate of claim 107, which is represented by the following formula: 0 K : o 8 o Bn < PNA Se \ we sor oO << PYYONSINONYY TT, > 5 0, H SepavCBA MeO Ng Oy NT ~Y n Xx o Y N Ol, R- < "a — N OMe MeO N i" 0 J we or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or - SOM.

116. An immunoconjugate represented by the following formula: ceA-{—cy? hu, wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 37,29, 30, 38, 33, and 34, or the polypeptide thereof of claim 55 or 56, covalently linked to Cy? through a cysteine residue; Wcislor2; Cy? is represented by the following formula: re PR YX C] - Soa oly + OF x2 were Y, Xx ? Col Ory > ow 0 0 6 or a pharmaceutically acceptable salt thereof, wherein: the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H or a (Ci- Cs)alkyl; and when it is a single bond, X is -H or an amine protecting moiety, Y is - OH or -SO:M, and M is H" or a cation; R*! is a (C1-Ce)alkyl; Reis -H or a (C1-Cs)alkyl; W’ is -NR¢"; R® is -(CH-CH;-0)1-R%; nis an integer from 2 to 6; Rk is -H or -Me; R* is a (C)-Cs)alkyl; Lc’ is represented by the following formula: Riz Rn 2s Ph Tay Q RyRy © Rh pa oO Rh Q Cod ha SOY SRE O RyRy Rao Rie © wherein: sl is the site covalently linked to the CBA and s2 is the site covalently linked to -S- group on Cy<2; Z is -C(=0)-NRg-,or -NRg-C(=0)-; Q is -H, a charged substituent, or an ionizable group; Ro, Rio, Rit, Ruz, Ris, Rig, Rao, Rai and Ray, for each occurrence, are independently -H or a (Ci-Cs)alkyl; q and r, for each occurrence, are independently an integer between 0 and 10; m and n are each independently an integer between 0 and 10; R" is -H or a (C,-Cs)alkyl; and P’ is an amino acid residue or a peptide containing 2 to 20 amino acid residues.

117. The immunoconjugate of claim 116, wherein P’ is a peptide containing 2 to 5 amino acid residues.

118. The immunoconjugate of claim 116 or 117, wherein P’ is selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Ile-Cit, Trp, Cit, Phe-Ala, Phe-N-tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe-Lys, D-Phe- Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala.

119. The immunoconjugate of claim 118, wherein P’ is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala.

120. The immunoconjugate of claim 116, wherein -Lc’- is represented by the following formula: 0 o st 2S ON SN X Ls Va Oo Q # YC dons, 0 H 2, ot 0 HAE find s1 N. N. NN s2 Yr era oO 121. The immunoconjugate of any one of claims 116-120, R¢ is H or Me; RX! is -(CHa)p- (CRRE)-, and R®? is -(CHa),-(CRIRE)-, wherein Rf and Re are each independently -H ora (C1-Cs)alkyl; and pis 0, 1, 2 or 3.

122. The immunoconjugate of claim 121, wherein Rf and R& are the same or different, and are selected from -H and -Me. > The immunoconjugate of claim 116, which is represented by the following formula: a SOM y Q S. N mA SoA pe o { OL hl ‘ N, 0.

0. N; > (QC o o Swe 2 o orig I Ker CR ” 0 0 we o. o s i 1 NNN N A Pe LC AE ll 0 s f-can Yo | H N, 0.

0. Nor 0 5 CC oC | © o we SOM List Tu 0 ANNONA EIS NA A Sw CBA x I he Yl H I~ ==N.

0.

0. N~, o > Ae OMe MeO’ XL | o 0 we or a pharmaceutically acceptable salt thereof, wherein the double line == between N and C represents a single bond or a double bond, provided that when it is a double bond, X is absent and Y is -H, and when it is a single bond, X is -H, and Y is -OH or - SOsM.

124. The immunoconjugate of any one of claims 116-123, wherein the double line == between N and C represents a double bond, X is absent and Y is -H.

125. The immunoconjugate of any one of claims 116-123, wherein the double line == between N and C represents a single bond, X is -H and Y is -SOsM.

126. The immunoconjugate of claim 125, wherein M is H", Na” or K™.

127. An immunoconjugate having the following formula: cBAH{—cy® ),. wherein: CBA is an antibody or antigen-binding fragment thereof of any one of claims 37,29, 30, 38, 33, and 34, or the polypeptide thereof of claim 55 or 56, covalently linked to Cy©3 through a cysteine residue; Wcislor2; Cy©3 is represented by the following formula: I ICPIGOLIIICU DY LUG 10110W He 10111 o N s + fs? Hie Le ca § 3 o R, Rq ! MeO, MARL . © No YY Ao SENNA A ved HE N o wherein: m’is 1 or2; R, and Ry, are each independently -H or a (C;-C3)alkyl; Lc’ is represented by the following formula: Riz Ri NM eh pty 1 Q RuR;,y O oO Rh 0, Cg Apt re SY ~~ “Wa {si O Rp Ry Rao Ris © wherein: sl is the site covalently linked to the CBA and s2 is the site covalently linked to -S- group on Cy©<3; Z is -C(=0)-NRg-,or -NRo-C(=0)-; Q is H, a charged substituent, or an ionizable group; Ro, Rio, Rit, Ria, Ria, Rig, Rao, R21 and Ry, for each occurrence, are independently -H or a (C;-Cs)alkyl; q and r, for each occurrence, are independently an integer between 0 and 10; m and n are each independently an integer between 0 and 10; RP is -H or a (C,-C3)alkyl; and P’ is an amino acid residue or a peptide containing 2 to 20 amino acid residues.

128. The immunoconjugate of claim 127, wherein P’ is a peptide containing 2 to 5 amino acid residues.

129. The immunoconjugate of claim 127 or 128, wherein P’ is selected from Gly-Gly-Gly, Ala-Val, Val-Ala, Val-Cit, Val-Lys, Phe-Lys, Lys-Lys, Ala-Lys, Phe-Cit, Leu-Cit, Lle-Cit, Trp, Cit, Phe-Ala, Phe-N-tosyl-Arg, Phe-N°-nitro-Arg, Phe-Phe-Lys, D-Phe- Phe-Lys, Gly-Phe-Lys, Leu-Ala-Leu, Ile-Ala-Leu, Val-Ala-Val, Ala-Leu-Ala-Leu (SEQ ID NO: 55), B-Ala-Leu-Ala-Leu (SEQ ID NO: 57), Gly-Phe-Leu-Gly (SEQ ID NO: 73), Val-Arg, Arg-Val, Arg-Arg, Val-D-Cit, Val-D-Lys, Val-D-Arg, D-Val-Cit, D-Val-Lys, D-Val-Arg, D-Val-D-Cit, D-Val-D-Lys, D-Val-D-Arg, D-Arg-D-Arg, Ala-Ala, Ala-D-Ala, D-Ala-Ala, D-Ala-D-Ala, Ala-Met, and Met-Ala.

130. The immunoconjugate of claim 129, wherein P’ is Gly-Gly-Gly, Ala-Val, Ala-Ala, Ala-D-Ala, D-Ala-Ala, or D-Ala-D-Ala.

131. The immunoconjugate of claim 127, wherein -Lc’- is represented by the following formula: 0 J st My As x Yin Ye Oo oO # rol 0 H 2, or OL I~ Ix IA { s1 N N. J NN N TY TA s2 Q wherein M is H or a cation.

132. The immunoconjugate of any one of claims 127-131, wherein m’ is 1 and R1 and Ra are both H.

133. The immunoconjugate of any one of claims 127-131, wherein m’ is 2 and R; and R> are both Me.

134. The immunoconjugate of claim 127, wherein the immunoconjugate is represented by the following formula: o A 0 A Mon canes” Hodom § 1 J we, Lg cana WI on b 4d ov ~ © Jwe. or cos (TC SN Lk Jk 0 N~ N N DM | 0 N N TY ey ; oO Ww oO o mo o 0 Tah 7 0 Uy or a pharmaceutically acceptable salt thereof, wherein DM is a drug moiety represented by the following formula: 0 Nt Lg MeO, AA, Ao hone ne. 3 7 ~ MeO HO H 135. A pharmaceutical composition comprising the antibody or antigen-binding fragment thereof of any one of claims 1-54, or the polypeptide of claim 55 or 56, or the immunoconjugate of any one of claims 60-134, and a pharmaceutically acceptable carrier.

136. A method for inhibiting the growth of a cell expressing CD123, comprising contacting the cell with the antibody or antigen-binding fragment thereof of any one of claims 1-54, or the polypeptide of claim 55 or 56, or the immunoconjugate of any one of claims 60-134, or the pharmaceutical composition of claim 135.

137. The method of claim 136, wherein said cell is a tumor cell.

138. The method of claim 137, wherein said cell is a leukemia cell or a lymphoma cell.

139. A method for treating a subject having cancer, wherein cells of the cancer expresses CD123, the method comprising administering to said subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of any one of claims 1-54, or the polypeptide of claim 55 or 56, or the immunoconjugate of any one of claims 60-134, or the pharmaceutical composition of claim 135.

140. The method of claim 139, wherein said cancer is leukemia or lymphoma.

141. The method of claim 139, wherein said cancer is selected from the group consisting of: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and Chronic lymphocytic leukemia (CLL).

142. The method of claim 141, wherein said cancer is acute myeloid leukemia (AML).

143. The method of claim 141, wherein said cancer is B-cell acute lymphoblastic leukemia (B-ALL).

144. A method for treating a cell-proliferative disorder in a subject, wherein cells of the cell-proliferative disorder expresses CD123, the method comprising administering to said subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of any one of claims 1-54, or the polypeptide of claim 55 or 56, or the immunoconjugate of any one of claims 60-134, or the pharmaceutical composition of claim 135, in an amount sufficient to treat said cell-proliferative disorder.

145. The method of claim 144, wherein said cell-proliferative disorder is selected from the group consisting of: acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), B-cell lineage acute lymphoblastic leukemia (B-ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), myelodysplastic syndrome, basic plasmacytoid DC neoplasm (BPDCN) leukemia, non-Hodgkin lymphomas (NHL), mantle cell lymphoma, and Hodgkin’s leukemia (HL).

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