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 .
Claims 9, 29, 44 and 112 are under consideration.
Rejections/Objections Withdrawn
The 35 USC 112(b) rejection of claims 9, 29, 44 and 112 has been withdrawn in view of claim amendments.
Rejections Maintained
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 9 and 112 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kovtun (Kovtun, et al., US 2017/0029514 A1; Published 02/02/2017, of record) in view of Walter (Walter, et al., Blood 2004, Vol 103, No. 11, of record) and Bogenberger (Bogenberger, et al., Leukemia 2014 Vol. 28, p 1657-1665, of record).
Kovtun teaches on the subject of immunoconjugates that bind to CD123 antigen (Kovtun, Abstract). Regarding the HC and LC limitations of claim 9, Kovtun teaches of an antibody comprising a HC of SEQ ID NO: 50 and a LC of SEQ ID NO: 51, which are 100% matches for instant SEQ ID NOs: 3 and 4, respectively (Kovtun, ¶ 0967). Regarding the ADC structure limitations of claim 9, Kovtun teaches that the immunoconjugate has a structure that is the same as the structure of claim 9 (Kovtun, ¶ 0240):
PNG
media_image1.png
324
1158
media_image1.png
Greyscale
… wherein the bond connecting the C (to which Y is attached) and the N (to which X is attached) is a single bond, X is hydrogen and Y is sulfonate (Kovtun, ¶ 0241) and Wc is 2 (Kovtun, ¶ 0245).
Kovtun teaches methods of treating cancer wherein the cancer comprises cancer cells of the cancer express CD123, the method comprising administering to said subject, inducing a human subject (¶ 0386), an effective amount of the immunoconjugate (Kovtun, claim 139) and that such cancers include AML (Kovtun, ¶ 0302). Kovtun also teaches that the immunoconjugate is effective at doses ranging from 0.8 mg/kg (Kovtun, ¶ 1029) to 0.1 micrograms/kg (Kovtun, ¶ 1034).
Additionally, Kovtun teaches that the immunoconjugates of Kovtun were successfully tested vs numerous blood cancer cell lines in xenograft models including the Katsumi-3 line (Kovtun, ¶ 1022-1030), the EOL-1 line (Kovtun, ¶ 1037-1042) and the MV4-11 line (Kovtun, ¶ 1046-1049) and none of these xenograft models included prior treatment and, as such, they are all examples of “front-line” therapy. Kovtun also teaches that treatment with a humanized anti-CD123 ADC caused an initial regression of tumor burden over time, reaching a nadir (low point) on day 27 (Kovtun, ¶ 1028).
Kovtun does not teach a method of treating hematological malignancies as a front-line therapy further comprising the administration of a BCL-2 inhibitor that is venetoclax and a hypomethylating agent that is azacytidine. Kovtun does not teach that the immunoconjugate is administered on a 28-day cycle or that the immunoconjugate is administered at a dose of 0.045 mg/kg.
Bogenberger teaches on the subject of synergistic molecular vulnerabilities enhancing hypomethylating agents in myeloid malignancies (Bogenberger, Abstract). Bogenberger teaches that the selective BCL-2 inhibitor ABT-199 (same as venetoclax) was able to shift the EC50 of azacytidine by at least 1.6-fold in 5 out of 7 cancer cell lines tested (Bogenberger, p 1660, Fig 2a). Bogenberger concludes by proposing clinical trials wherein BCL-2 family inhibitors are combined with azacytidine.
Walter teaches on the subject of tumor cell resistance to ADCs as well as strategies to overcome said resistance (Walter, Abstract). One such ADC taught by Walter is Gemtuzumab ozogamicin (GO), which targets CD33 and was developed for treatment of AML (Walter, p 4276, ¶ 2). Walter teaches that BCL-2 antisense oligonucleotides can increase GO-induced cytotoxicity in HL-60 cells, suggesting that antiapoptotic proteins may limit the efficacy of the ADC (Walter, p 4282, ¶ 4). Walter further teaches that in a direct test of this possibility, Walter and colleagues found that BCL-2 and BCL-xL overexpression is associated with GO resistance (Walter, P 48282, ¶ 4; p 4282, Fig 4a).
It would be prima facie obvious to one of ordinary skill in the art to combine the method of treating hematological malignancies including AML taught by Kovtun, said method comprising administration of the immunoconjugate of Kovtun with administration of venetoclax and azacytidine in view of the teachings of Walter and Bogenberger and to use the resultant combination of the immunoconjugate of Kovtun, azacytidine and venetoclax as a front-line therapy. The net result of this combination would be a front-line method of treating a hematological malignancy such as AML, said method comprising administration of azacytidine, venetoclax and the anti-CD123 immunoconjugate of Kovtun. One of ordinary skill in the art would be motivated to make this combination in order to better treat AML. One of ordinary skill in the art would have a reasonable expectation of success treating hematological malignancies including AML using a combination of azacytidine, venetoclax and the anti-CD123 immunoconjugate of Kovtun as a front-line therapy because: 1) Kovtun teaches that the anti-CD123 immunoconjugate of Kovtun is used to treat hematological malignancies, including AML, 2) Walter teaches that inhibition of BCL-2 is known to both counteract resistance to ADCs, 3) Bogenberger teaches that venetoclax is both a selective inhibitor of BCL-2 and also increases the anti-cancer effects of the hypomethylating agent azacytidine and 4) the numerous successful xenograft studies described in the Kovtun reference (none of which involved prior treatment) would lead one of skill in the art to realize the immunoconjugates of Kovtun are suitable for front-line use.
Regarding the “unfit AML” limitation of claim 9, the instant Specification states that “unfit AML” refers to a subject having AML who is ineligible for intensive therapy and that there are numerous different measures for determining if a subject has “unfit AML” (Specification, ¶ 0119). The instant Specification also discloses that AML patients deemed “fit” are judged to tolerate intensive treatment, which typically comprises a combination of the chemotherapeutics cytarabine and an anthracycline (typically daunorubicin) followed by high dose cytarabine and results in a median duration of remission of 1 year and 25-35% cures, whereas “unfit” AML patients receive venetoclax (a BCL-2 inhibitor) and azacitidine (a hypomethylating agent), with the majority of “unfit” AML patients relapsing (Specification, ¶ 0006). It would therefore be prima facie obvious to one of ordinary skill in the art to administer the combination of the immunoconjugate of Kovtun, venetoclax and azacytidine as front-line therapy for “unfit AML”. One of ordinary skill in the art would be motivated to do this in order to treat AML in a patient ineligible to receive intensive chemotherapeutic treatment received by “fit” AML patients. One of ordinary skill in the art would have a reasonable expectation of success administering the immunoconjugate of Kovtun, venetoclax and azacytidine as a front line therapy to a patient having “unfit AML”, because this method is an immunoconjugate-based method and not an intensive chemotherapeutic-based method and one of ordinary skill in the art would reasonably deduce that a patient ineligible for intensive chemotherapeutic therapy may be eligible for immunoconjugate-based therapy due to the drastically different mechanisms of action that chemotherapeutics and immunoconjugates have.
It would be prima facie obvious to one of ordinary skill in the art to administer the instant combination on a 28-day cycle in view of the teachings of Kovtun. One of ordinary skill in the art would be motivated to administer the instant combination on a 28-day cycle in order to maintain the anti-tumor effect of the ADC over time. Kovtun teaches that regression of tumor burden caused by the immunoconjugate reaches a low point at about 27 days, and this creates a motivation to readminister the immunoconjugate of Kovtun on a cycle, with the exact cycle being a matter of routine optimization, which is within the purview of one of skill in the art. One of ordinary skill in the art would have a reasonable expectation of success starting with the knowledge that the treatment reaches a low point at about 27 days and arriving at a 28-day cycle through routine experimentation because routine experimentation is within the purview of one of ordinary skill in the art. Additionally, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F. 2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see MPEP 2144.05). Further with respect to optimal dosing regimens, it is not inventive to discover such regimens by routine experimentation when general conditions of a claim are disclosed in the prior art. See in re Aller, 220 F.2d 545, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05(11)).
It would be prima facie obvious to one of ordinary skill in the art to administer to the patient in need of treatment a dosage of immunoconjugate of 0.045 mg/kg. One of ordinary skill in the art would be motivated to administer at these doses in order to provide the patients an optimal dosage of the immunoconjugate of Kovtun. One of ordinary skill in the art would have a reasonable expectation of success administering, to a patient in need thereof, the immunoconjugate of Kovtun on a 28 day cycle, with the dose of immunoconjugate being dosed at 0.045 mg/kg because Kovtun teaches doses between 0.0001 mg/kg (same as 0.1 micrograms/kg) and 0.8 mg/kg and that significant therapeutic effects were observed in mice at both the high and low ends of this range (See Kovtun, Col. 362, Table and Kovtun, Col 364, Table), establishing a motivation to optimize the doses to some value within this range and routine optimization is within the purview of one of skill in the art. Additionally, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F. 2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (see MPEP 2144.05). Further with respect to optimal dosing regimens, it is not inventive to discover such regimens by routine experimentation when general conditions of a claim are disclosed in the prior art. See in re Aller, 220 F.2d 545, 456, 105 USPQ 233, 235 (CCPA 1955) (see MPEP 2144.05(11)).
Response to Arguments
Applicant's arguments filed 3/20/2026 have been fully considered but they are not persuasive.
Applicant argues that the prima facie case of obvious in this rejection is in error because Kovtun, Walter and Bogenberger (individually or combined) do not teach, suggest or motivate one of skill in the art to the critical combination of limitations of claim 9. Additionally, Applicant also argues the Examiner has not presented a proper motivation to arrive at the instant claimed method of using the immunoconjugate with a DAR of 2 with venetoclax and azacitidine for the treatment of unfit AML with the immunoconjugate being administered at a dose of 0.045 mg/kg once in a 28-day cycle.
Applicant also argues that Kovtun is silent with respect to administration of immunoconjugate at any particular cycles or intervals. Applicant argues, with respect to the 28-day dosing cycle, that Kovtun teaches that regression of tumor burden reached a low point at day 27 but the immunoconjugate was still highly active at day 27, which Applicant argues would cause one of skill in the art to surmise the immunoconjugate is no longer effective against the remaining tumor cells and, as such, would not be motivated to administer the same compound again on day 28.
In response, the conclusion that the immunoconjugates of Kovtun were “highly active” at day 27 and this conclusion was based on determine %T/C values for the mice treated using the immunoconjugates of Kovtun at day 27 (Kovtun, p. 1028). Kovtun teaches that tumor burden in the mice was measured using an AML cell line engineered to express luciferase, which allows for quantification of tumor burden using a live animal imager, which detects the bioluminescence produced by the luciferase expressed by the AML cell line of Kovtun (Kovtun, p 1023). Kovtun teaches that %T/C (tumor growth inhibition value) is calculated by dividing the median bioluminescence of the treated group by the median bioluminescence of the control group (Kovtun, p 1025). Because these bioluminescence measurements are taken at day 27, the tumor burden reduction observed in the treatment group is reflective of the cumulative anti-tumor effect exerted by the immunoconjugate from days 1 through 27 and not the specific activity of the immunoconjugate of Kovtun at day 27. Also, Kovtun’s teaching that the rate of tumor burden reduction reaches a low point at day 27 following injection of the immunoconjugate provides more than sufficient teaching and motivation for one of skill in the art to administer the instant claimed immunoconjugate at 28-day cycles. Kovtun teaches that the rate of tumor burden reduction reached a low point at 27 days after injection. This does not mean that the subject’s tumor is completely eliminated after the 27 days. One of skill in the art would be motivated to re-administer the immunoconjugate at day 28 so that the immunoconjugate can continue to exert its anti-tumor effect on the patient’s remaining tumor cells.
Applicant re-states the examiner’s reasoning that, since immunoconjugates are mechanistically different from chemotherapies, one of skill in the art would expect that a patient ineligible for intensive chemotherapy could receive an immunoconjugate and argues that “this allegation is entirely speculative and conclusory”. Applicant states that the motivation to combine references must be supported by evidence or technical reasoning showing why administering the immunoconjugate in conjunction with venetoclax and azacitidine would be an obvious choice for unfit AML.
In response, the mechanistic differences between chemotherapies and immunoconjugates are both well-known and highly significant. Chemotherapeutics are exert toxicity on both tumor cells as well as healthy cells. Immunotherapeutics, on the other hand, are targeted therapeutics designed to exert toxicity on tumor cells only. The killing of healthy cells by chemotherapeutics is widely known to cause a myriad of deleterious side effects in patients. If a patient is ineligible for chemotherapeutic treatment due to that particular patient’s inability to tolerate these side effects, an immunotherapeutic is a natural alternative, as the immunotherapeutic does kill cancer cells but not target/kill healthy cells, thus avoiding side effects caused by the killing of the patient’s healthy cells. Regarding the venetoclax and azacitidine administered in the instant claimed method, the combined teachings of Walter and Bogenberger demonstrate that venetoclax and azacitidine work in concert with one another to increase ADC effectiveness, providing one of skill in the art sufficient motivation to include administration of venetoclax and azacitidine in the instant claimed method.
Claims 9, 44 and 112 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kovtun (Kovtun, et al., US 2017/0029514 A1; Published 02/02/2017, of record) in view of Walter (Walter, et al., Blood 2004, Vol 103, No. 11, of record) and Bogenberger (Bogenberger, et al., Leukemia 2014 Vol. 28, p 1657-1665, of record) as applied to claims 9 and 112 above and in further view of Prescriber’s Digital Reference (PDR 2013; URL: https://www.pdr.net/drug-summary/Vidaza-azacitidine-1664; accessed 12/11/2021, of record)
The combined teachings of Kovtun, Walter and Bogenberger are discussed above.
The combined teachings of Kovtun, Walter and Bogenberger do not teach that the azacytidine is administered in a 28-day cycle.
The PDR teaches that 75 mg/m2 every day for a 4-week (28 day) cycle is the recommended dosage for azacytidine for both subcutaneous and intravenous administration (PDR 2013, p 2, entire page).
It would be prima facie obvious to one of ordinary skill in the art form a method of treating unfit AML in a human subject comprising administration of the anti CD123 ADC of claim 9, venetoclax and azacytidine, wherein the azacytidine is administered at a dosage of 75 mg/m2 intravenously or subcutaneously on a 28-day cycle in view of the teachings of PDR. One of ordinary skill in the art would be motivated to dose the azacytidine this way in order to use the azacytidine in a manner consistent with established prescribing guidelines. One of ordinary skill in the art would have a reasonable expectation of success administering azacytidine component in the method of treating unfit AML in a human subject described above at a dosage of 75 mg/m2 intravenously or subcutaneously on a 28-day cycle because this is the dosage regimen recommended by the PDR.
Response to Arguments
Applicant provides no arguments specific to this rejection
Claims 9, 29 and 112 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kovtun (Kovtun, et al., US 2017/0029514 A1; Published 02/02/2017, of record) in view of Walter (Walter, et al., Blood 2004, Vol 103, No. 11, of record) and Bogenberger (Bogenberger, et al., Leukemia 2014 Vol. 28, p 1657-1665, of record) as applied to claims 9 and 112 above and in further view of FDA (FDA, 4/2016, Reference ID: 3915259, of record)
The combined teachings of Kovtun, Walter and Bogenberger are discussed above.
The combined teachings of Kovtun, Walter and Bogenberger do not teach that the venetoclax is administered at a dosage of 400 mg/day.
FDA teaches that 400 mg/day is the maximum recommended daily dosage daily dosage for venetoclax (FDA, p 2, ¶ 4).
It would be prima facie obvious to one of ordinary skill in the art form a method of treating unfit AML in a human subject comprising administration of the anti CD123 ADC of claim 9, venetoclax and azacytidine, wherein the venetoclax is administered at a dosage of 400 mg/day in view of the teachings of FDA. One of ordinary skill in the art would be motivated to dose the venetoclax this way in order to use the venetoclax in a manner consistent with established prescribing guidelines and to get the maximum clinical benefit of the venetoclax without using a dose that is higher than what is recommended. One of ordinary skill in the art would have a reasonable expectation of success administering the venetoclax component administered in the method of treating unfit AML in a human subject described above at a dosage of 400 mg/day because this is the dosage regimen recommended by the FDA.
Response to Arguments
Applicant provides no arguments specific to this rejection other than stating the PDR reference does not remedy the alleged deficiencies of Kovtun, Walter and Bogenberger.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 9, 29, 44 and 112 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 11,701,428 B2 in view of Kovtun (Kovtun, et al., US 2017/0029514 A1; Published 02/02/2017).
The ‘428 patent teaches methods of treating hematological malignancies comprising the administration of an immunoconjugate identical to the instant claimed immunoconjugate in combination with venetoclax and/or azacytidine, with the main difference being that the patented method is directed to relapsed and/or refractory malignancies, whereas the instant claimed method is a front-line therapy.
Regarding instant claim 9, patented claim 6 is directed to an immunoconjugate comprising an identical linker-drug moiety linked to an antibody with HC and LC sequences that are the same as the instant claimed sequences. Regarding instant claim 9, patented claim 8 is directed to administering the same immunoconjugate on a 28-day cycle. Regarding instant claim 9, patented claim 10 is directed to doses of 0.045 mg/kg for the immunoconjugate on 28-day cycles. Regarding instant claim 29, patented claim 11 is directed to 400 mg doses of venetoclax. Regarding instant claim 44, patented claim 12 is directed to administering azacytidine on a 28-day cycle. Regarding instant claim 9, patented claims 1-4 are directed to methods of treating AML.
The ‘428 patent does not teach that the method of treating a hematological malignancy comprising administration of the immunoconjugate of the ‘428 patent as well as venetoclax and azacytidine is a front-line therapy. The ‘428 patent does not teach that the hematological malignancy is unfit AML.
Kovtun teaches on the subject of immunoconjugates that bind to CD123 antigen (Kovun, Abstract). The immunoconjugates of Kovtun are identical to the immunoconjugates of the ‘428 patent as well as the instant claimed immunoconjugates with respect to: 1) CDR sequences of the antibody (Kovtun, ¶ 0618), 2) VH and VL sequences of the antibody (Kovtun, ¶ 0618), 3) HC and LC sequences of the antibody (Kovtun, ¶ 0967) and 4) the structure of the linker-drug moiety of the immunoconjugate (Kovtun, ¶ 0240-0245; Kovtun ¶ 0311). Kovtun also teaches that the immunoconjugates of Kovtun are administered in methods of treating a wide range of hematological malignancies, including AML, MDS, ALL, B-ALL and BPDCN (Kovtun, ¶ 0302). Additionally, Kovtun teaches that the immunoconjugates of Kovtun were successfully tested vs numerous blood cancer cell lines in xenograft models including the Katsumi-3 line (Kovtun, ¶ 1022-1030), the EOL-1 line (Kovtun, ¶ 1037-1042) and the MV4-11 line (Kovtun, ¶ 1046-1049) and none of these xenograft models included prior treatment and, as such, they are all examples of “front-line” therapy.
It would be prima facie obvious to one of ordinary skill in the art to apply the method of treating relapsed or refractory AML taught by the ‘428 patent, wherein the method comprises administering the immunoconjugate of the ‘428 patent in combination with venetoclax and azacytidine to the treatment AML as a front-line therapy in view of the teachings of Kovtun. One of ordinary skill in the art would be motivated to do this in order to treat AML in a front-line therapy. One of ordinary skill in the art would have a reasonable expectation of success applying the method of the ‘428 patent to treat AML as a front-line therapy because the Kovtun reference teaches that an identical anti-CD123 immunoconjugate was successfully tested in a number of different in vivo xenograft models, all of these models modeled “front-line” therapy and one of skill in the art would reasonably deduce that these in vivo results could be extrapolated to a human subject.
Regarding the “unfit AML” limitation of claim 9, the instant Specification states that “unfit AML” refers to a subject having AML who is ineligible for intensive therapy and that there are numerous different measures for determining if a subject has “unfit AML” (Specification, ¶ 0119). The instant Specification also discloses that AML patients deemed “fit” are judged to tolerate intensive treatment, which typically comprises a combination of the chemotherapeutics cytarabine and an anthracycline (typically daunorubicin) followed by high dose cytarabine and results in a median duration of remission of 1 year and 25-35% cures, whereas “unfit” AML patients receive venetoclax (a BCL-2 inhibitor) and azacitidine (a hypomethylating agent), with the majority of “unfit” AML patients relapsing (Specification, ¶ 0006). It would therefore be prima facie obvious to one of ordinary skill in the art to apply the method of treating AML taught by the ‘428 patent, said method comprising administration of the immunoconjugate of the ‘428 patent with venetoclax and azacytidine as a front-line therapy for “unfit AML”.
One of ordinary skill in the art would be motivated to do this in order to treat AML in a patient ineligible to receive intensive chemotherapeutic treatment received by “fit” AML patients. One of ordinary skill in the art would have a reasonable expectation of success administering the immunoconjugate of Kovtun, venetoclax and azacytidine as a front line therapy to a patient having “unfit AML”, because this method is an immunoconjugate-based method and not an intensive chemotherapeutic-based method and one of ordinary skill in the art would reasonably deduce that a patient ineligible for intensive chemotherapeutic therapy may be eligible for immunoconjugate-based therapy due to the drastically different mechanisms of action that chemotherapeutics and immunoconjugates have. One of ordinary skill in the art would have a reasonable expectation of success applying the method of treating AML taught by the ‘428 patent to AML in a patient having “unfit AML” because this method is an immunoconjugate-based method and not an intensive chemotherapeutic-based method and one of ordinary skill in the art would reasonably deduce that a patient ineligible for intensive chemotherapeutic therapy may be eligible for immunoconjugate-based therapy due to the drastically different mechanisms of action that chemotherapeutics and immunoconjugates have.
Response to Arguments
Applicant's arguments filed 12/10/2025 have been fully considered but they are not persuasive.
Applicant argues that this rejection relies on Kovtun’s Xenograft models to supply a “front line” teaching. Applicant further argues that xenograft efficacy in treatment-naïve mice does not establish that the same regimen will be effective in human AML patients who are medically unfit for intensive [chemotherapeutic] therapy. Applicant additionally argues that the examiner’s reliance on Kovtun’s xenografts improperly conflates absence of prior treatment in a model with a teaching that the method is suitable for a clinically distinct human subpopulation.
In response, first and foremost, using murine in vivo xenograft models of the efficacy of a drug to predict that drug’s in vivo efficacy in humans is highly routine in the art. Therefore, even though murine in vivo xenograft models of a drug’s efficacy do not perfectly model that drug’s in vivo efficacy in humans, such in vivo murine models are deemed sufficient similar to in vivo human systems that these murine xenograft models are very widely used in the art as models of drug performance in humans. Additionally, as stated and articulated above, Kovtun’s xenograft models demonstrate the instant claimed immunoconjugate as being effective for a wide range of hematological malignancies, including AML. This wide range of hematological malignancies treatable with the instant claimed immunoconjugate would naturally cause one of skill in the art to deduce that the claimed immunoconjugate affects blood cancer cells (including AML cells) via general mechanism of action and not, for example, a highly specific mechanism acting only on blood cancer cells associated with highly specific pathology(ies). This general mechanism of action would naturally lead one of skill in the art to deduce that the instant claimed immunoconjugate is likely to be able to treat unfit AML because Kovtun teaches the instant claimed immunoconjugate would be effective vs unfit AML because unfit AML is caused by cancerous blood cells and Kovtun teaches that the instant claimed immunoconjugate exerts a general, anti-cancer effect on a very wide range of blood cancer cells.
Conclusion
Claims 9, 29, 44 and 112 are rejected.
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sydney Van Druff whose telephone number is (571)272-2085. The examiner can normally be reached 10 am - 6 pm.
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, Julie Wu can be reached on 571-272-5205. 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.
/SYDNEY VAN DRUFF/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643
Prosecution Insights