DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Claims 1-13, 22, 24-29 are pending and being examined.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
2. Claims 1-13, 22, 24-29 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 1 and 8 recite: “wherein an associated VH an VL specifically bind to CD20 or a subunit thereof”. This phrase does not refer back to the VH and VL regions previously recited in claim 1, therefore appears to be a separate VH and VL. It is unclear how to what these VH and VL are “associated” with.
Claims 1 and 8 subsequently recite “wherein the VH comprises three immunoglobulin complementarity determining regions: HCDR1, HCDR2, HCDR3, and the VL comprises…” As stated above, it appears there are two sets of VH and VL in the claims and it is unclear which set of VH and VL this phrase is referring to – the VH and VL from the phrase “heavy chain variable region (VH) and an IgM constant region and two light chains, each comprising a light chain variable region (VL) and a light chain constant region”, or the VH and VL from the phrase “wherein an associated VH an VL specifically bind to CD20 or a subunit thereof”? Dependent claims are rejected for depending upon and encompassing rejected claims 1 and 8.
Examiner Suggestion: Amend claims 1 and 8 to recite: “wherein the VH and VL specifically bind to CD20”.
3. Claim 25 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claim 25 depends from claim 1 and recites “the heavy chain comprises SEQ ID NO…” Claim 1 recites plural heavy chains: “each binding unit comprises two IgM heavy chains” and recites plural light chains: “and two light chains”. Therefore, it is unclear which heavy chain and which light chain is being referenced in claim 25.
Examiner Suggestion: Amend claim 25 to recite “wherein the heavy chains comprise[[s]] SEQ ID NO:61 and the light chains comprise[[s]] SEQ ID NO:62.”
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
4. Claim(s) 1, 2, 12, 22, and 24-29 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/059380, Keyt et al; in view of Baliga et al (Blood, November 13, 2019; 134, Suppl. 1; p. 1574); ClinicalTrials.gov NCT04082936 (Revision History October 4, 2019); Le Tourneau et al (Journal of National Cancer Institute, 2009, 101:708-720); and Bannerji et al (Blood, November 5, 2020, 136(Supplement_1):42).
Keyt teaches a method of treating cancer in a human comprising administering a T cell engaging multimeric binding molecule comprising an anti-CD20 IgM pentamer with a modified J-chain comprising an anti-CD3 scFv, wherein the cancer is non-Hodgkin’s lymphoma (Figures, 1, 4, 5, 8, 22, 27; p. 44-47, 97, 110; Examples 1, and 6-15; Table 10; claims 67-76).
Figure 1:
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Keyt teaches the sequences of the anti-CD20 IgM, J-chain, and anti-CD3 scFv that are 100% identical to the instantly claimed sequences (see sequence alignments below):
Structure
Instantly claimed sequence
Keyt sequences
CD20 IgM VH CDRs 1-3
(1.5.3 antibody)
55+56+57
64, 82
CD20 IgM VL CDRs 1-3
(1.5.3 antibody)
58+59+60
68, 84
CD3 scFv
31
98, 100, 102
J chain
7
26, 23, 92, 90, 25, 1
J-chain
34
102
CD20 IgM heavy chain
(1.5.3 antibody)
61
82
CD20 IgM light chain
(1.5.3 antibody)
62
84
In Example 3, Keyt teaches: “The half-life of IgMs in human plasma is estimated to be around 2-3 days and shorter still in mice (FIG. 9). This is significantly shorter than for IgGs, which interact with the neonatal Fc receptor (FcRn) and are recycled after endocytosis enabling a much longer half-life of roughly 21 days. In order to increase the half-life of IgMs, tethering of scFvs to either terminus of the J-chain was performed, without significantly altering the effector functions of IgMs such as CDC (FIG. 7).”
Keyt exemplifies administering 100 ug of the multimeric binding molecule to mice to assess pharmacokinetics (Examples 6 and 7; Figure 17). Keyt exemplifies determining the half life (AUC ug/ml/hr) of the multimeric binding molecules in mice (Figure 22 and 27; Example 14). Keyt exemplifies administering multimeric binding molecule to CD34+ humanized mice and determined B-lymphocyte levels were reduced to <10% of the pre-dose levels for both 1.5.3-V15J15-HSA (K573P) and 1.5.3-V15J15-HAS wt with as little as 10 ug dosed at a single time (Example 15; Figure 28).
Keyt teaches “there is a need for binding molecules with increased avidity that will provide increased potency so that lower dosage levels can be used, thereby preventing the occurrence of immune-related adverse events, while still achieving effective blockade of T- cell inhibitory signaling pathways” (p. 3).
Keyt teaches: “Actual dosage levels of the active ingredients in the pharmaceutical compositions of the present invention may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. The selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions of the present invention employed, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts” (p. 110-111).
Keyt does not teach the various doses and administration regimens claimed:
Administering a dosage of 75 mg to 600 mg of the T cell-engaging multimeric binding molecule (claim 1);
Administering 100 mg to 300 mg (claim 2);
Wherein the subject previously received a cancer therapy comprising chemotherapy or immunotherapy (claim 12), and the cancer is relapsed or refractory or CD20+ cancer (claim 27).
Baliga teaches clinically administering IGM-2323, a T cell-engaging multimeric binding molecule comprising an anti-CD20 IgM pentamer with a modified J chain comprising anti-CD3 scFv, to relapsed/refractory non-Hodgkin’s lymphoma patients. Baliga teaches the T cell-engaging multimeric binding molecule binds CD20 antigen with more than 1000-fold increased avidity and mediates CDC of CD20-expressing cells with greater than 100-fold higher potency when compared to the corresponding IgG bispecific antibody. IGM-2323 demonstrates vastly reduced cytokine release in vitro and in vivo, with at least equivalent T cell dependent killing of CD20-expressing target cells, providing a potentially safer and more effective bispecific format than IgG-based T cell CD20xCD3 bispecifics. Data indicates that IgM-based bispecific can induce T cell engagement at very potent cytotoxicity that can be dissociated from the cytokine release, unlike what has been observed with other bispecific antibodies. In vivo efficacy studies in humanized NSG mice indicated that doses as low as 3 ug/mouse cause compete B cell elimination. Similarly, bispecific IgM completely depletes circulating B cells in cynomolgus monkeys at doses of 300 mg/kg. Durable depletion of B cell in spleen and lymphoid tissues was noted in the primate studies without any observable adverse effects despite repeated doses at the highest dose tested, 25 mg/kg. Cytokine levels were only minimally increased during these primate studies.
NCT04082936 teaches clinically treating relapsed/refractory non-Hodgkin’s lymphoma patients with IMG-2323. Patients treated are CD20+ (Study Design; Detailed Description; Conditions), and relapsed or refractory to at least two prior systemic treatment regimens including anti-CD20 chemo-immunotherapy regimen (Key Inclusion Criteria). NCT04082936 teaches that in their preclinical studies, they observed activity of IMG-2323 against rituximab resistant cells carrying low levels of CD20, and observed much lower cytokine release with IGM-2323 relative to comparable IgG CD20xCD3 bispecifics, which is expected to reduce the risk of serious adverse events from cytokine release syndrome (CRS) (Detailed Description).
NCT04082936 teaches conducting a dose-escalation phase and a dose-expansion phase. In the dose-escalation phase, patients will receive IGM-2323 infusion on Days 1, 8, 15, of a 21-day cycle and treated with 4 cycles. Patients benefitting from therapy can receive up to 8 cycles or longer with good response. Dose escalation will be guided by the observed incidence of dose limiting cytotoxicities (DLTs) at each dose level. In the dose expansion-phase, patients will receive IGM-2323 infusion at a recommended Phase 2 dose (RP2D) and schedule to be determined after reviewing all available response and safety data (Arms and Interventions). NCT04082936 teaches monitoring adverse events during treatment (Outcome Measures).
Le Tourneau teaches standard protocol for determining dose escalation in cancer clinical trials based on DLTs. Le Tourneau teaches a principal goal of phase I dose escalation study is to establish the recommended dose and/or schedule of an experimental drug for efficacy in testing Phase 2 trials (p. 708, col. 1). Le Tourneau reviews the known different methods of dose escalation for phase I cancer clinical trials of single agents, including the traditional 3+3 design (p. 709-710). Le Tourneau teaches the general principal design for dose escalation methods is to escalate or de-escalate the dose with diminishing fractions of the preceding dose depending on the absence or presence of severe toxicity in the previous cohort of treated patients (Figure 2, A). The simple up-and-down design converges to a dose that corresponds to a probability of sever toxicity of approximately 50% which is higher than the 33% threshold commonly accepted in most Phase I cancer clinical trials (p. 709, col. 1-2). Le Tourneau teaches the 3+3 design remains the prevailing method for conducting Phase I cancer clinical trials (p. 709, col. 2). Le Tourneau explains for 3+3 design (p. 709-710) (bold emphasis added):
“The traditional 3+3 design remains the prevailing method for conducting phase I cancer clinical trials ( 7 ). It requires no modeling of the dose–toxicity curve beyond the classical assumption for cytotoxic drugs that toxicity increases with dose. This rule-based design proceeds with cohorts of three patients; the first cohort is treated at a starting dose that is considered to be safe based on extrapolation from animal toxicological data, and the subsequent cohorts are treated at increasing dose levels that have been fixed in advance ( Figure 2, B ). Historically, dose escalation has followed a modified Fibonacci sequence in which the dose increments become smaller as the dose increases (eg, the dose first increases by 100% of the preceding dose, and thereafter by 67%, 50%, 40%, and 30%–35% of the preceding doses). In most cases, the prespecified dose levels do not fit the exact Fibonacci sequence as described in the 12th century ( 5 ). If none of the three patients in a cohort experiences a dose-limiting toxicity, another three patients will be treated at the next higher dose level. However, if one of the first three patients experiences a dose-limiting toxicity, three more patients will be treated at the same dose level. The dose escalation continues until at least two patients among a cohort of three to six patients experience dose-limiting toxicities (ie, ≥33% of patients with a dose-limiting toxicity at that dose level). The recommended dose for phase II trials is conventionally defined as the dose level just below this toxic dose level.”
Le Tourneau further teaches the accelerated titration design, which combines features from the traditional 3+3 design and the model-based design. The accelerated titration design comprises allowing dose escalation within a single patient at each cycle of treatment until DLT is observed. Allowing for intrapatient dose escalation is appealing because it gives some patients the opportunity to be treated at higher and presumably more effective doses (p. 710, col. 2 to p. 711, col. 2; Figure 2, C).
Le Tourneau summarizes the various methods of dose escalation in Figure 2 demonstrating known methods of decreasing/maitnaining the dose in response to observed DLT symptoms, or increasing the dose when there are no DLTs, benefit is observed, and arriving at the recommended dose (RD):
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245
645
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223
645
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229
645
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Le Tourneau teaches the advantages of the various dose escalation methods (Table 2), wherein 3+3 is easy to implement and safe, and provides some data on pharmacokinetic interpatient variability; and wherein the acerated titration design provides more rapid dose escalation, and data from all patients, cumulative toxicity, and intrapatient variability can be fit to a model to establish the RP2D (recommended phase 2 dose).
Bannerji demonstrates conducting a FIH dose escalation and dose expansion Phase I trial for treating relapsed/refractory non-Hodgkin’s lymphoma patients with a IgGCD20xCD3 bispecific antibody. Patients were treated with a starting fixed dose ranging from 0.03-320 mg. Bannerji teaches that no DLTs were reported during dose escalation and maximum tolerated dose (MTD) was not reached with the bispecific antibody at doses up to 320 mg weekly (Results). Bannerji teaches the most frequent treatment-related adverse event (AE) was cytokine release syndrome (CRS) (fever) and chills. Most of the CRS events occurred during the first 2 weeks of step-up dosing and resolved within a median of 2 days with supportive care (Results). Dexamethasone premedication mitigated step-up dosing risk of CRS and allowed for administration up to 320 mg weekly without DLTs (Conclusions). Based on evaluation of antitumor activity and PK, a RP2DR was identified for dose expansion cohorts.
Administering the IgMCD20xCD3 bispecific antibody at a dose in the range of 75 mg – 600 mg, or 100 mg – 300 mg:
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the T cell engaging multimeric binding molecule (IgMCD20xCD3 bispecific antibody) of Keyt at a dose within the range of 75 mg – 600 mg, or 100-300 mg, to treat cancer. One would have been motivated to and have a reasonable expectation of success to because: (1) Le Tourneau teaches identifying starting doses considered to be safe based on extrapolation from animal toxicological data, and subsequently increasing the fixed doses in dose escalation methods for cancer clinical trials, (2) Keyt and Baliga determined doses of IGM-2323 or IgMCD20xCD3 bispecific antibody safe based on PK data in mice and monkeys, including doses of 10 µg or 3µg/mouse, 300 mg/kg in monkeys, or repeated doses of 25 mg/kg in monkeys that did not result in serious cytokine release; and teach that IGM-2323 or IgMCD20xCD3 bispecific antibody demonstrate, significantly, vastly reduced cytokine release in vitro and in vivo, providing a safer and more effective bispecific antibody format than IgG-based T cell CD20xCD3 bispecifics; and (3) Bannerji exemplifies administering starting doses of IgG-based CD20xCD3 bispecific antibody in the range of 0.03 mg to 320 mg weekly to treat cancer in a clinical Phase I dose-escalation study and successfully arriving at a starting does of 320 mg weekly for Phase 2 dose escalation studies.
In the test of whether it is “obvious to try” there must be:
(1) a finding in the art at the time of filing of the invention that there had been a recognized problem or need in the art;
(2) a finding that there had been a finite number of identified, predictable potential solutions to the recognized need or problem;
(3) a finding that one of ordinary skill in the art could have pursued the known potential solutions with a reasonable expectation of success.
Given: (1) the recognized need to treat cancer, particularly relapsed/refractory non-Hodgkin’s lymphoma, with the IgMCD20xCD3 bispecific antibody of Keyt, and with a safe starting dose; and (2) the known solution of identifying the safe starting dose through animal PK data (taught by Le Tourneau, Keyt and Baliga), wherein Keyt and Baliga determined through animal testing that doses of the T cell engaging multimeric binding molecule were safe even at high and repeated doses (i.e., 10 or 3ug in mice, 320 mg/kg and 25 mg/kg in monkeys) due to its vastly reduced cytokine release properties, and (3) the knowledge of starting doses in relevant treatment methods of 0.03 – 320 mg of IgGCD20xCD3 bispecific antibody as safe doses; one of skill in the art could have pursued administering the IgMCD20xCD3 bispecific antibody of Keyt at a dose within the range of 75 mg – 600 mg, or 100-300 mg, to treat cancer with a reasonable expectation of success.
5. Claim(s) 3-11 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/059380, Keyt et al; Baliga et al (Blood, November 13, 2019; 134, Suppl. 1; p. 1574); ClinicalTrials.gov NCT04082936 (Revision History October 4, 2019); Le Tourneau et al (Journal of National Cancer Institute, 2009, 101:708-720); and Bannerji et al (Blood, November 5, 2020, 136(Supplement_1):42); as applied to claims 1, 2, 12, 22, 24-29 above, and further in view of Patel et al (Blood, 2019, 134(Supplement_1):4079).
Keyt; Baliga; ClinicalTrials.gov NCT04082936; Le Tourneau; and Bannerji (the combined references) teach a method of treating relapsed/refractory non-Hodgkin’s lymphoma comprising administering the IgMCD20xCD3 bispecific antibody at a dose in the range of 75 mg – 600 mg, or 100-300 mg, and routine methods of dose escalation and dose expansion in clinical trial, as set forth above.
The combined references do not teach:
Patient received prior dose of the T cell-engaging multimeric binding molecule and the prior dose was <100 mg (claim 3) or the prior dose comprise 2 or 3 prior doses of the T cell-engaging multimeric binding molecule and were each <100mg (claim 4);
Administering: (a) a first dose of 10 mg to 50 mg of the T cell-engaging multimeric binding molecule to the subject, then (b) administering the dose of 75 mg to 600 mg (claim 5), then 5 days later administering another 75 mg to 600 mg (claim 6); wherein the dose in step (b) is 100 mg to 300 mg, or 300 mg (claim 7);
(a) Administering the T cell-engaging multimeric binding molecule at a determined dose; (b) monitoring the subject for an administration-related symptom; and (c)(i) administering the T cell-engaging multimeric binding molecule to the subject at the same or a reduced dosage relative to the dose in (a) if the subject had the administration-related symptom, and (c)(ii) administering the T cell-engaging multimeric binding molecule to the subject at an increased dose relative to (a) if the subject did not have the administration-related symptom (claim 8), wherein the administration-related symptom comprises chills, fever (claim 9);
Further comprising repeating steps (b) and (c) one or more times (claim 10); and
Wherein the increased dose of the T cell-engaging multimeric binding molecule in step (c)(ii) is: 25-1000% greater than the determined dose in (a), 30-300 mg; 100-300 mg, or 100 – 300 mg (claim 11).
Patel exemplifies applying a 3+3 dose escalation method (taught by Le Tourneau) to Phase I first-in-human (FIH) trial for a CD2-xCD3 bispecific antibody in refractory/relapsed non-Hodgkin’s lymphoma patients. Patel teaches (Methods):
The study is a first-in-human, multi-center, open-label, phase 1, dose-escalation study in subjects with R/R NHL and R/R CLL with a standard 3 + 3 design. The primary objectives are to determine safety, tolerability, and the maximum tolerated dose (MTD) or recommended dose of XmAb13676. Secondary objectives include preliminary anti-tumor activity and PK/PD of XmAb13676. This study is designed in two parts: Part A, escalating dose cohorts that establish an initial priming dose as part of repeated weekly infusions at a fixed dose in a 28-day cycle; and Part B, with a dosing schedule consisting of a priming dose on C1D1 , established in Part A, followed by escalated dose(s) on subsequent weeks. Cytokine Release Syndrome (CRS) prophylaxis with dexamethasone was mandated prior to each administration of XmAb13676. Treatment was continued for 2 cycles or longer if there was evidence of therapeutic benefit.
Patel teaches the treatment-related serious adverse events used to determine toxicity and MTD include symptoms of cytokine release syndrome (fever), chills, and hypotension (Table 1A).
In summary: Le Tourneau, Patel, and Bannerji teach and demonstrate established dose escalation methods to determine a CD20xCD3 bispecific antibody’s MTD and RP2DR for Phase II dose expansion phase studies in relapsed/refractory non-Hodgkin’s lymphoma patients, wherein their dose escalation methods rely upon monitoring patient anti-tumor response, adverse events (CRS, fever, chills, hypotension), and DLTs after dose escalation, and either: (1) increasing dose if no AE’s and DLTs are observed, (2) mitigating observed AEs to maintain subsequent doses, or (3) decreasing the dose if DLTs or AEs are observed. Keyt, Baliga, and NCT04082936 recognize the need to determine safe and effective doses of bispecific anti-CD20IgMxCD3 to treat cancer patients, including non-Hodgkin’s lymphoma patients, in order to minimize cytokine release symptoms and avoid DLTs; and NCT04082936 demonstrates applying phase I dose escalation studies to IGM-2323 in order to determine the RP2D for Phase 2 expansion dose studies.
Administering multiple doses that escalate in subsequent doses, wherein a first dose is <100 mg (i.e., 10-20 mg), a second dose is higher (i.e., 75-600 mg or 100-300 mg, or 300 mg) and administered at least 5 days after the first dose; and the third dose is 75-600 mg given at least 5 days after the second dose (i.e., 3 weeks or cycles with dose escalation after the first dose) (claims 3-7):
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the T cell engaging multimeric binding molecule (IgMCD20xCD3 bispecific antibody) of Keyt multiple times (weekly in multiple cycles) and at escalating doses as recited in instant claims 3-7. One would have been motivated to and have a reasonable expectation of success to because: (1) the combined references identified safe doses of IgMCD20xCD3 bispecific antibody for cancer treatment and render obvious the claimed doses falling within the claimed dose ranges, (2) the combined references teach administering the antibody repeatedly weekly, where NCT04082936 teaches administering the antibody on days 1, 8, and 15 in 21 day cycles for at least 4 cycles (i.e., more than 5 days between doses), or longer if patients are benefitting and do not show DLTs, and NCT04082936 teaches administering the antibody in a Phase I dose escalation study to determine the recommended Phase 2 dose (RP2D) for Phase 2 dose expansion studies; (3) Le Tourneau reviews established dose escalation methods where patient dose is increased in subsequent cycles to determine MTD and RP2D; and (4) Patel and Bannerji successfully demonstrate practicing dose escalation methods to determine a CD20xCD3 bispecific antibody’s MTD and RP2DR for Phase II dose expansion trial.
Given: (1) the recognized need to repeat administration of IgMCD20xCD3 bispecific antibody in cycles, including weekly (which is more than 5 days between doses), for cancer treatment; (2) the need to perform dose escalation methods in the Phase I clinical trial of IgMCD20xCD3 bispecific antibody in order to identify the antibody’s MTD and RP2DR for Phase II dose expansion; (3) the known and successful solution of established dose escalation methods to identify the MTD and RP2D for Phase II dose expansion; one of skill in the art could have pursued administering the IgMCD20xCD3 bispecific antibody of the combined references weekly in multiple 21-day cycles and increase the doses weekly or by cycle from 10-50 mg, to <100 mg, to 75-600 mg or 300 mg, with a reasonable expectation of success.
Administering the IgMCD20xCD3 bispecific antibody at a determined dose; monitoring for an administration-related symptom; and either (1) administering the bispecific antibody at the same or a reduced dosage relative to the determined dose if the subject had the administration-related symptom, or (2) administering the bispecific antibody at an increased dose relative to the determined dose if the subject did not have the administration-related symptom, wherein the administration-related symptom comprises chills, fever; and repeating these steps one or more times (claims 8-10):
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to administer the IgMCD20xCD3 bispecific antibody of the combined references at a determined dose (i.e., safe dose) to a cancer patient, monitor the patient for adverse events (AEs) such as cytokine release syndrome (CRS), fever, chills, and hypotension, then either: (1) repeat the dose or lower the dose if the patient has an AE, or (2) increase the dose if the subject did not experience an AE; then repeat monitoring and dose adjustment steps. One would have been motivated to, and have a reasonable expectation of success to, because: (1) the combined references identified and rendered obvious predetermined safe doses of IgMCD20xCD3 bispecific antibody for cancer treatment for the reasons stated above, recognizing that CRS is an AE/DLT to avoid (2) the combined references teach administering the antibody repeatedly weekly, where NCT04082936 teaches administering the antibody on days 1, 8, and 15 in 21 day cycles for at least 4 cycles, or longer if patients are benefitting and do not show DLTs, and NCT04082936 teaches administering the antibody in a Phase I dose escalation study to determine the recommended Phase 2 dose (RP2D) for Phase 2 dose expansion studies; (4) Le Tourneau reviews established dose escalation methods to determine MTD and RP2D, wherein subsequent patient doses are increased if there are no AE or DLTs, or wherein subsequent patient doses are maintained or lowered when the patient displays AE or DLTs; (4) Patel and Bannerji successfully demonstrate practicing dose escalation methods to determine a CD20xCD3 bispecific antibody’s MTD and RP2DR for Phase II dose expansion trial; and (5) Patel demonstrates successfully monitoring AEs during repeated dosage of bispecific antibody, including CRS, fever, chills, and hypotension, in order to determine the MTD.
Increasing the dose of the bispecific antibody IgMCD20xCD3 bispecific antibody by 25%-1000% greater than the determined dose, by 30-300mg, by 100-300mg, or by 100-300mg, when the monitored patient exhibits no AE after the determined dose (claim 11):
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to increase the subsequent dose of IgMCD20xCD3 bispecific antibody by increments within 30 to 300 mg or by 25-1000% if the patient does not exhibit AEs/DLTs. One would have been motivated to, and have a reasonable expectation of success to, because the combined references identified and rendered obvious safe doses of IgMCD20xCD3 bispecific antibody for cancer treatment for the reasons stated above and falling within the claimed range, and provide motivation to and reasonable expectation of success to increase the dose until the MTD or RP2D is identified in the absence of unmanageable AEs/DLTs, for the reasons stated above.
6. Claim(s) 13 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/059380, Keyt et al; Baliga et al (Blood, November 13, 2019; 134, Suppl. 1; p. 1574); ClinicalTrials.gov NCT04082936 (Revision History October 4, 2019); Le Tourneau et al (Journal of National Cancer Institute, 2009, 101:708-720); and Bannerji et al (Blood, November 5, 2020, 136(Supplement_1):42); as applied to claims 1, 2, 12, 22, and 24-29 above, and further in view of Salles et al (Adv. Ther. 2017, 34:2232-2273).
Keyt; Baliga; NCT04082936; Le Tourneau; and Bannerji (the combined references) teach a method of treating cancer patients previously treated with chemotherapy and anti-CD20 immunotherapy, including relapsed/refractory non-Hodgkin’s lymphoma comprising administering the IgMCD20xCD3 bispecific antibody at a dose in the range of 75 mg – 600 mg, or 100-300 mg, and routine methods of dose escalation and dose expansion in clinical trial, as set forth above. NCT04082936 and Bannerji, specifically teach refractory/relapsed non-Hodgkin’s lymphoma patients in need of treatment are relapsed or refractory to prior anti-CD20 therapy. Baliga teaches IGM-2323 shows highly potent T cell dependent cytotoxicity, even on cells with very low surface expression of CD20 and on rituximab-resistant variants of Ramos cells, and suggests treating relapsed/refractory NHL in a phase I dose-escalation study.
The combined references do not teach that the prior anti-CD20 immunotherapy was rituximab (claim 13).
Salles teaches that rituximab is an anti-CD20 immunotherapy routinely used to treat non-Hodgkin’s lymphoma (NHL) and many patients develop resistance (p. 2252, col. 2). Salles teach the need to produce the next generation of anti-CD20 antibody with different mechanism of action for therapy of patients who relapsed on rituximab (p. 2253, col. 1).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to treat NHL patient relapsed/refractory to rituximab in the method of the combined references. One would have been motivated to, and have a reasonable expectation of success to, because the combined references teach treating a population of relapsed/refractory NHL patients who failed prior anti-CD20 immunotherapy, and Salles teach rituximab is the anti-CD20 immunotherapy that NHL patients become relapsed or refractory to.
SEQ ID NOs:55+56+57 aligned with Keyt SEQ ID NO:64:
ID BDU65252 standard; protein; 122 AA.
XX
AC BDU65252;
XX
DT 18-MAY-2017 (first entry)
XX
DE Anti-CD20 1.5.3 antibody heavy chain variable region, SEQ ID 64.
XX
KW B-lymphocyte antigen CD20; CD20; acute lymphoblastic leukemia;
KW acute myelogenous leukemia; age related macular degeneration;
KW alzheimers disease; antiarthritic; antibody; antibody therapy;
KW antiinflammatory; astrocytoma; bladder cancer; breast tumor; cancer;
KW central nervous system tumor; chronic lymphocytic leukemia;
KW chronic myelocytic leukemia; colorectal tumor; cytostatic;
KW esophagus tumor; glioma; heavy chain variable region;
KW hematological neoplasm; hodgkins disease; immunosuppressive; leukemia;
KW liver tumor; lymphoma; melanoma; meningioma; multiple myeloma;
KW myelodysplastic syndrome; nasopharyngeal carcinoma; neuroprotective;
KW non-Hodgkin’s lymphoma ; non-small-cell lung cancer; nootropic;
KW oligodendroglioma; ophthalmological; ovary tumor; pancreas tumor;
KW renal tumor; rheumatoid arthritis; stomach tumor; therapeutic;
KW thyroid tumor.
XX
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 64; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is an anti-CD20 antibody heavy
CC chain variable region, used in the invention for treating above mentioned
CC diseases.
XX
SQ Sequence 122 AA;
ALIGNMENT:
Query Match 89.4%; Score 206.4; Length 122;
Best Local Similarity 46.5%;
Matches 40; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 GYSFTSYWI--------------GIIYPGDSDTRYSPSFQG------------------- 27
||||||||| ||||||||||||||||||
Db 26 GYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSITTAYLQWSS 85
Qy 28 -------------HPSYGSGSPNFDY 40
|||||||||||||
Db 86 LKASDTAMYYCARHPSYGSGSPNFDY 111
SEQ ID NO:55+56+57 aligned with Keyt SEQ ID NO:82:
ID BDU65270 standard; protein; 575 AA.
XX
AC BDU65270;
XX
DT 18-MAY-2017 (first entry)
XX
DE Anti-CD20 1.5.3 IgM antibody heavy chain, SEQ ID 82.
XX
KW B-lymphocyte antigen CD20; CD20; Immunoglobulin M;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; glioma; heavy chain;
KW hematological neoplasm; hodgkins disease; immunosuppressive; leukemia;
KW liver tumor; lymphoma; melanoma; meningioma; multiple myeloma;
KW myelodysplastic syndrome; nasopharyngeal carcinoma; neuroprotective;
KW non-Hodgkin’s lymphoma ; non-small-cell lung cancer; nootropic;
KW oligodendroglioma; ophthalmological; ovary tumor; pancreas tumor;
KW renal tumor; rheumatoid arthritis; stomach tumor; therapeutic;
KW thyroid tumor.
XX
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
DR N-PSDB; BDU65269.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 82; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is an anti-CD20 1.5.3 IgM
CC antibody heavy chain, used in the invention for treating above mentioned
CC diseases.
XX
SQ Sequence 575 AA;
ALIGNMENT:
Query Match 89.4%; Score 206.4; Length 575;
Best Local Similarity 46.5%;
Matches 40; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 GYSFTSYWI--------------GIIYPGDSDTRYSPSFQG------------------- 27
||||||||| ||||||||||||||||||
Db 26 GYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISADKSITTAYLQWSS 85
Qy 28 -------------HPSYGSGSPNFDY 40
|||||||||||||
Db 86 LKASDTAMYYCARHPSYGSGSPNFDY 111
SEQ ID NO:58+59+60 aligned with Keyt SEQ ID NO:68:
ID BDU65256 standard; protein; 112 AA.
XX
AC BDU65256;
XX
DT 18-MAY-2017 (first entry)
XX
DE Anti-CD20 1.5.3 antibody light chain variable region, SEQ ID 68.
XX
KW B-lymphocyte antigen CD20; CD20; acute lymphoblastic leukemia;
KW acute myelogenous leukemia; age related macular degeneration;
KW alzheimers disease; antiarthritic; antibody; antibody therapy;
KW antiinflammatory; astrocytoma; bladder cancer; breast tumor; cancer;
KW central nervous system tumor; chronic lymphocytic leukemia;
KW chronic myelocytic leukemia; colorectal tumor; cytostatic;
KW esophagus tumor; glioma; hematological neoplasm; hodgkins disease;
KW immunosuppressive; leukemia; light chain variable region; liver tumor;
KW lymphoma; melanoma; meningioma; multiple myeloma;
KW myelodysplastic syndrome; nasopharyngeal carcinoma; neuroprotective;
KW non-Hodgkin’s lymphoma ; non-small-cell lung cancer; nootropic;
KW oligodendroglioma; ophthalmological; ovary tumor; pancreas tumor;
KW renal tumor; rheumatoid arthritis; stomach tumor; therapeutic;
KW thyroid tumor.
XX
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 68; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is an anti-CD20 antibody light
CC chain variable region, used in the invention for treating above mentioned
CC diseases.
XX
SQ Sequence 112 AA;
ALIGNMENT:
Query Match 84.4%; Score 133.3; Length 112;
Best Local Similarity 40.5%;
Matches 32; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RSSQSLVYSDGNTYLS---------------KISNRFS---------------------- 23
|||||||||||||||| |||||||
Db 24 RSSQSLVYSDGNTYLSWLQQRPGQPPRLLIYKISNRFSGVPDRFSGSGAGTDFTLKISRV 83
Qy 24 ----------VQATQFPLT 32
|||||||||
Db 84 EAEDVGVYYCVQATQFPLT 102
SEQ ID NO:58+59+60 aligned with Keyt SEQ ID NO:84:
ID BDU65272 standard; protein; 219 AA.
XX
AC BDU65272;
XX
DT 18-MAY-2017 (first entry)
XX
DE Anti-CD20 1.5.3 IgM antibody light chain, SEQ ID 84.
XX
KW B-lymphocyte antigen CD20; CD20; Immunoglobulin M;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; glioma;
KW hematological neoplasm; hodgkins disease; immunosuppressive; leukemia;
KW light chain; liver tumor; lymphoma; melanoma; meningioma;
KW multiple myeloma; myelodysplastic syndrome; nasopharyngeal carcinoma;
KW neuroprotective; non-Hodgkin’s lymphoma ; non-small-cell lung cancer;
KW nootropic; oligodendroglioma; ophthalmological; ovary tumor;
KW pancreas tumor; renal tumor; rheumatoid arthritis; stomach tumor;
KW therapeutic; thyroid tumor.
XX
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 84; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is an anti-CD20 1.5.3 IgM
CC antibody light chain, used in the invention for treating above mentioned
CC diseases.
XX
SQ Sequence 219 AA;
Query Match 84.4%; Score 133.3; Length 219;
Best Local Similarity 40.5%;
Matches 32; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RSSQSLVYSDGNTYLS---------------KISNRFS---------------------- 23
|||||||||||||||| |||||||
Db 24 RSSQSLVYSDGNTYLSWLQQRPGQPPRLLIYKISNRFSGVPDRFSGSGAGTDFTLKISRV 83
Qy 24 ----------VQATQFPLT 32
|||||||||
Db 84 EAEDVGVYYCVQATQFPLT 102
SEQ ID NO:31 aligned with Keyt SEQ ID NO:98:
RESULT 7
BDU65286
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BDU65286 standard; protein; 483 AA.
XX
AC BDU65286;
XX
DT 18-MAY-2017 (first entry)
XX
DE Cancer treating related fusion protein (V15J15), SEQ ID 98.
XX
KW B-lymphocyte antigen CD20; CD20; Immunoglobulin J;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; fusion protein; glioma;
KW hematological neoplasm; hodgkins disease; immunosuppressive; leukemia;
KW liver tumor; lymphoma; melanoma; meningioma; multiple myeloma;
KW myelodysplastic syndrome; nasopharyngeal carcinoma; neuroprotective;
KW non-Hodgkin’s lymphoma ; non-small-cell lung cancer; nootropic;
KW oligodendroglioma; ophthalmological; ovary tumor; pancreas tumor;
KW renal tumor; rheumatoid arthritis; stomach tumor; therapeutic;
KW thyroid tumor.
XX
OS Homo sapiens.
OS Synthetic.
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
DR N-PSDB; BDU65285.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 98; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is a fusion protein comprising
CC albumin binding domain (ABD), human J chain and anti-CD20 antibody, used
CC in the invention for treating cancer.
XX
SQ Sequence 483 AA;
Query Match 100.0%; Score 1275; Length 483;
Best Local Similarity 100.0%;
Matches 241; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 20 QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHY 79
Qy 61 NQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSAYYDYDGFAYWGQGTLVTVSS120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 80 NQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSAYYDYDGFAYWGQGTLVTVSS139
Qy 121 GGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKR180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 140 GGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKR199
Qy 181 LIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGGTKVEI240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 200 LIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGGTKVEI259
Qy 241 K 241
|
Db 260 K 260
SEQ ID NO:31 aligned with Keyt SEQ ID NO:102:
RESULT 11
BDU65290
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
ID BDU65290 standard; protein; 1012 AA.
XX
AC BDU65290;
XX
DT 18-MAY-2017 (first entry)
XX
DE Cancer treating related fusion protein, SEQ 102.
XX
KW B-lymphocyte antigen CD20; CD20; HSA; Immunoglobulin J;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; fusion protein; glioma;
KW hematological neoplasm; hodgkins disease; human serum albumin;
KW immunosuppressive; leukemia; liver tumor; lymphoma; melanoma; meningioma;
KW multiple myeloma; myelodysplastic syndrome; nasopharyngeal carcinoma;
KW neuroprotective; non-Hodgkin’s lymphoma ; non-small-cell lung cancer;
KW nootropic; oligodendroglioma; ophthalmological; ovary tumor;
KW pancreas tumor; renal tumor; rheumatoid arthritis; stomach tumor;
KW therapeutic; thyroid tumor.
XX
OS Homo sapiens.
OS Synthetic.
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
DR N-PSDB; BDU65289.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 102; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is a fusion protein comprising
CC human serum albumin (HSA), human J chain and anti-CD20 antibody, used in
CC the invention for treating cancer.
XX
SQ Sequence 1012 AA;
Query Match 100.0%; Score 1275; Length 1012;
Best Local Similarity 100.0%;
Matches 241; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 20 QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHY 79
Qy 61 NQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSAYYDYDGFAYWGQGTLVTVSS120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 80 NQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSAYYDYDGFAYWGQGTLVTVSS139
Qy 121 GGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKR180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 140 GGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKR199
Qy 181 LIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGGTKVEI240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 200 LIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGGTKVEI259
Qy 241 K 241
|
Db 260 K 260
SEQ ID NO:7 aligned with Keyt SEQ ID NO:26:
RESULT 8
BDU65214
ID BDU65214 standard; protein; 157 AA.
XX
AC BDU65214;
XX
DT 18-MAY-2017 (first entry)
XX
DE Homo sapiens J chain protein, SEQ ID 26.
XX
KW Immunoglobulin J; acute lymphoblastic leukemia;
KW acute myelogenous leukemia; age related macular degeneration;
KW alzheimers disease; antiarthritic; antibody therapy; antiinflammatory;
KW astrocytoma; bladder cancer; breast tumor; cancer;
KW central nervous system tumor; chronic lymphocytic leukemia;
KW chronic myelocytic leukemia; colorectal tumor; cytostatic;
KW esophagus tumor; glioma; hematological neoplasm; hodgkins disease;
KW immunosuppressive; leukemia; liver tumor; lymphoma; melanoma; meningioma;
KW multiple myeloma; myelodysplastic syndrome; nasopharyngeal carcinoma;
KW neuroprotective; non-Hodgkin’s lymphoma ; non-small-cell lung cancer;
KW nootropic; oligodendroglioma; ophthalmological; ovary tumor;
KW pancreas tumor; renal tumor; rheumatoid arthritis; stomach tumor;
KW therapeutic; thyroid tumor.
XX
OS Homo sapiens.
OS Synthetic.
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Claim 39; SEQ ID NO 26; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is a Homo sapiens J chain
CC protein, used in the invention for treating above mentioned diseases.
XX
SQ Sequence 157 AA;
Query Match 100.0%; Score 729; Length 157;
Best Local Similarity 100.0%;
Matches 137; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QEDERIVLVDNKCKCARITSRIIRSSEDPNEDIVERNIRIIVPLNNRENISDPTSPLRTR 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QEDERIVLVDNKCKCARITSRIIRSSEDPNEDIVERNIRIIVPLNNRENISDPTSPLRTR 60
Qy 61 FVYHLSDLCKKCDPTEVELDNQIVTATQSNICDEDSATETCYTYDRNKCYTAVVPLVYGG120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 FVYHLSDLCKKCDPTEVELDNQIVTATQSNICDEDSATETCYTYDRNKCYTAVVPLVYGG120
Qy 121 ETKMVETALTPDACYPD 137
|||||||||||||||||
Db 121 ETKMVETALTPDACYPD 137
SEQ ID NO:34 aligned with Keyt SEQ ID NO:102:
ID BDU65290 standard; protein; 1012 AA.
XX
AC BDU65290;
XX
DT 18-MAY-2017 (first entry)
XX
DE Cancer treating related fusion protein, SEQ 102.
XX
KW B-lymphocyte antigen CD20; CD20; HSA; Immunoglobulin J;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; fusion protein; glioma;
KW hematological neoplasm; hodgkins disease; human serum albumin;
KW immunosuppressive; leukemia; liver tumor; lymphoma; melanoma; meningioma;
KW multiple myeloma; myelodysplastic syndrome; nasopharyngeal carcinoma;
KW neuroprotective; non-Hodgkin’s lymphoma ; non-small-cell lung cancer;
KW nootropic; oligodendroglioma; ophthalmological; ovary tumor;
KW pancreas tumor; renal tumor; rheumatoid arthritis; stomach tumor;
KW therapeutic; thyroid tumor.
XX
OS Homo sapiens.
OS Synthetic.
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
DR N-PSDB; BDU65289.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 102; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is a fusion protein comprising
CC human serum albumin (HSA), human J chain and anti-CD20 antibody, used in
CC the invention for treating cancer.
XX
SQ Sequence 1012 AA;
Query Match 100.0%; Score 5275; Length 1012;
Best Local Similarity 100.0%;
Matches 993; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 20 QVQLVQSGAEVKKPGASVKVSCKASGYTFISYTMHWVRQAPGQGLEWMGYINPRSGYTHY 79
Qy 61 NQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSAYYDYDGFAYWGQGTLVTVSS120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 80 NQKLKDKATLTADKSASTAYMELSSLRSEDTAVYYCARSAYYDYDGFAYWGQGTLVTVSS139
Qy 121 GGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKR180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 140 GGGGSGGGGSGGGGSDIQMTQSPSSLSASVGDRVTITCSASSSVSYMNWYQQKPGKAPKR199
Qy 181 LIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGGTKVEI240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 200 LIYDTSKLASGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQWSSNPPTFGGGTKVEI259
Qy 241 KGGGGSGGGGSGGGGSQEDERIVLVDNKCKCARITSRIIRSSEDPNEDIVERNIRIIVPL300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 260 KGGGGSGGGGSGGGGSQEDERIVLVDNKCKCARITSRIIRSSEDPNEDIVERNIRIIVPL319
Qy 301 NNRENISDPTSPLRTRFVYHLSDLCKKCDPTEVELDNQIVTATQSNICDEDSATETCYTY360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 320 NNRENISDPTSPLRTRFVYHLSDLCKKCDPTEVELDNQIVTATQSNICDEDSATETCYTY379
Qy 361 DRNKCYTAVVPLVYGGETKMVETALTPDACYPDGGGGSGGGGSGGGGSDAHKSEVAHRFK420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 380 DRNKCYTAVVPLVYGGETKMVETALTPDACYPDGGGGSGGGGSGGGGSDAHKSEVAHRFK439
Qy 421 DLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGD480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 440 DLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGD499
Qy 481 KLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEE540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 500 KLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEE559
Qy 541 TFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKAS600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 560 TFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKAS619
Qy 601 SAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLE660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 620 SAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLE679
Qy 661 CADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVES720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 680 CADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVES739
Qy 721 KDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAK780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 740 KDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAK799
Qy 781 VFDEFKPLVEEPQNLIKQNCELFKQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGK840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 800 VFDEFKPLVEEPQNLIKQNCELFKQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGK859
Qy 841 VGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALE900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 860 VGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALE919
Qy 901 VDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFA960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 920 VDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFA979
Qy 961 AFVEKCCKADDKETCFAEEGKKLVAASQAALGL 993
|||||||||||||||||||||||||||||||||
Db 980 AFVEKCCKADDKETCFAEEGKKLVAASQAALGL 1012
SEQ ID NO:61 aligned with Keyt SEQ ID NO:82:
ID BDU65270 standard; protein; 575 AA.
XX
AC BDU65270;
XX
DT 18-MAY-2017 (first entry)
XX
DE Anti-CD20 1.5.3 IgM antibody heavy chain, SEQ ID 82.
XX
KW B-lymphocyte antigen CD20; CD20; Immunoglobulin M;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; glioma; heavy chain;
KW hematological neoplasm; hodgkins disease; immunosuppressive; leukemia;
KW liver tumor; lymphoma; melanoma; meningioma; multiple myeloma;
KW myelodysplastic syndrome; nasopharyngeal carcinoma; neuroprotective;
KW non-Hodgkin’s lymphoma ; non-small-cell lung cancer; nootropic;
KW oligodendroglioma; ophthalmological; ovary tumor; pancreas tumor;
KW renal tumor; rheumatoid arthritis; stomach tumor; therapeutic;
KW thyroid tumor.
XX
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
DR N-PSDB; BDU65269.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 82; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is an anti-CD20 1.5.3 IgM
CC antibody heavy chain, used in the invention for treating above mentioned
CC diseases.
XX
SQ Sequence 575 AA;
Query Match 100.0%; Score 3050; Length 575;
Best Local Similarity 100.0%;
Matches 575; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRY 60
Qy 61 SPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHPSYGSGSPNFDYWGQGTLVTV120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SPSFQGQVTISADKSITTAYLQWSSLKASDTAMYYCARHPSYGSGSPNFDYWGQGTLVTV120
Qy 121 SSGSASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKNNSDISSTRGFPS180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SSGSASAPTLFPLVSCENSPSDTSSVAVGCLAQDFLPDSITFSWKYKNNSDISSTRGFPS180
Qy 181 VLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQHPNGNKEKNVPLPVIAELPPKVSVFVP240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VLRGGKYAATSQVLLPSKDVMQGTDEHVVCKVQHPNGNKEKNVPLPVIAELPPKVSVFVP240
Qy 241 PRDGFFGNPRKSKLICQATGFSPRQIQVSWLREGKQVGSGVTTDQVQAEAKESGPTTYKV300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PRDGFFGNPRKSKLICQATGFSPRQIQVSWLREGKQVGSGVTTDQVQAEAKESGPTTYKV300
Qy 301 TSTLTIKESDWLSQSMFTCRVDHRGLTFQQNASSMCVPDQDTAIRVFAIPPSFASIFLTK360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TSTLTIKESDWLSQSMFTCRVDHRGLTFQQNASSMCVPDQDTAIRVFAIPPSFASIFLTK360
Qy 361 STKLTCLVTDLTTYDSVTISWTRQNGEAVKTHTNISESHPNATFSAVGEASICEDDWNSG420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 STKLTCLVTDLTTYDSVTISWTRQNGEAVKTHTNISESHPNATFSAVGEASICEDDWNSG420
Qy 421 ERFTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNLRESATITCLVTGFSP480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 ERFTCTVTHTDLPSPLKQTISRPKGVALHRPDVYLLPPAREQLNLRESATITCLVTGFSP480
Qy 481 ADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSILTVSEEEWNTGETYTCVVAHE540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 ADVFVQWMQRGQPLSPEKYVTSAPMPEPQAPGRYFAHSILTVSEEEWNTGETYTCVVAHE540
Qy 541 ALPNRVTERTVDKSTGKPTLYNVSLVMSDTAGTCY 575
|||||||||||||||||||||||||||||||||||
Db 541 ALPNRVTERTVDKSTGKPTLYNVSLVMSDTAGTCY 575
SEQ ID NO:62 aligned with Keyt SEQ ID NO:84:
ID BDU65272 standard; protein; 219 AA.
XX
AC BDU65272;
XX
DT 18-MAY-2017 (first entry)
XX
DE Anti-CD20 1.5.3 IgM antibody light chain, SEQ ID 84.
XX
KW B-lymphocyte antigen CD20; CD20; Immunoglobulin M;
KW acute lymphoblastic leukemia; acute myelogenous leukemia;
KW age related macular degeneration; alzheimers disease; antiarthritic;
KW antibody; antibody therapy; antiinflammatory; astrocytoma;
KW bladder cancer; breast tumor; cancer; central nervous system tumor;
KW chronic lymphocytic leukemia; chronic myelocytic leukemia;
KW colorectal tumor; cytostatic; esophagus tumor; glioma;
KW hematological neoplasm; hodgkins disease; immunosuppressive; leukemia;
KW light chain; liver tumor; lymphoma; melanoma; meningioma;
KW multiple myeloma; myelodysplastic syndrome; nasopharyngeal carcinoma;
KW neuroprotective; non-Hodgkin’s lymphoma ; non-small-cell lung cancer;
KW nootropic; oligodendroglioma; ophthalmological; ovary tumor;
KW pancreas tumor; renal tumor; rheumatoid arthritis; stomach tumor;
KW therapeutic; thyroid tumor.
XX
OS Unidentified.
XX
CC PN WO2017059380-A1.
XX
CC PD 06-APR-2017.
XX
CC PF 30-SEP-2016; 2016WO-US055041.
XX
PR 30-SEP-2015; 2015US-0235518P.
XX
CC PA (IGMB-) IGM BIOSCIENCES INC.
XX
CC PI Keyt B, Presta LG, Baliga R;
XX
DR WPI; 2017-234830/31.
XX
CC PT New binding molecule comprises immunoglobulin (Ig)M, IgA, IgG/IgM or
CC PT IgG/IgA antibody with modified J-chain comprises absorption,
CC PT distribution, metabolism and/or excretion (ADME)-modulating moiety, used
CC PT for treating cancer.
XX
CC PS Example 11; SEQ ID NO 84; 184pp; English.
XX
CC The present invention relates to a novel binding molecule comprises
CC immunoglobulin (Ig) M, IgA, IgG/IgM or IgG/IgA antibody with modified J-
CC chain useful for treating cancer. The invention further relates to a
CC pharmaceutical composition comprises an effective amount of the binding
CC molecule and a pharmaceutically acceptable carrier for treating
CC rheumatoid arthritis, age-related macular degeneration and Alzheimer's
CC disease. The cancer is chosen from hematologic cancer (e.g., leukemia,
CC acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous
CC leukemia, or chronic lymphocytic leukemia), lymphoma (e.g., Hodgkin's
CC lymphoma or non-Hodgkin's lymphoma, myeloma, or myelodysplastic
CC syndrome), an epithelial cancer (e.g., melanoma, non-small-cell lung,
CC nasopharyngeal, colorectal, liver, urinary bladder, ovarian, gastric,
CC esophageal, pancreatic, renal, thyroid or breast cancer), or a central
CC nervous system cancer (e.g., glioma, astrocytoma, meningioma, neuroma and
CC oligodendroglioma). The present sequence is an anti-CD20 1.5.3 IgM
CC antibody light chain, used in the invention for treating above mentioned
CC diseases.
XX
SQ Sequence 219 AA;
Query Match 100.0%; Score 1134; Length 219;
Best Local Similarity 100.0%;
Matches 219; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVMTQTPLSSPVTLGQPASISCRSSQSLVYSDGNTYLSWLQQRPGQPPRLLIYKISNRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVMTQTPLSSPVTLGQPASISCRSSQSLVYSDGNTYLSWLQQRPGQPPRLLIYKISNRF 60
Qy 61 SGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCVQATQFPLTFGGGTKVEIKRTVAAPSV120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGAGTDFTLKISRVEAEDVGVYYCVQATQFPLTFGGGTKVEIKRTVAAPSV120
Qy 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 FIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSL180
Qy 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
|||||||||||||||||||||||||||||||||||||||
Db 181 SSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 219
7. Conclusion: No claim is allowed.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Laura B Goddard/Primary Examiner, Art Unit 1642