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 .
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied, and constitute the complete set presently being applied to the instant application.
Response to Arguments
Applicant's arguments filed 2/20/2026 regarding the claim rejections under 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant’s position is that the 1) references of Chen, Najibi, Sims, or Le Tourneau, either alone or in combination, fail to teach or suggest the combination of FLT3, IFNg, and SEQ ID NO: 9 and the order of administration, 2) there is insufficient motivation to combine, 3) a person skilled in the art would not have a reasonable expectation of success in combining the cited references, and 4) the Applicant has demonstrated substantially improved and unexpected results.
Regarding 1), both the former and current claim set are rendered obvious based upon the teachings of Chen, Najibi, Sims, and Le Tourneau; see art rejections below.
Regarding 2), per MPEP 2143: The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. In Ball Aerosol v. Ltd. Brands, 555 F.3d 984, 89 USPQ2d 1870 (Fed. Cir. 2009), the Federal Circuit offered additional instruction as to the need for an explicit analysis. The Federal Circuit explained that the Supreme Court’s requirement for an explicit analysis does not require record evidence of an explicit teaching of a motivation to combine in the prior art.
"[T]he analysis that "should be made explicit" refers not to the teachings in the prior art of a motivation to combine, but to the court’s analysis. . . . Under the flexible inquiry set forth by the Supreme Court, the district court therefore erred by failing to take account of ‘the inferences and creative steps,’ or even routine steps, that an inventor would employ and by failing to find a motivation to combine related pieces from the prior art." Ball Aerosol, 555 F.3d at 993, 89 USPQ2d at 1877.
The above references teach administration of therapeutic combinations, particular those that activate the immune system, to combat the same types of cancers. This is sufficient motivation for one skilled in the art to combine the claimed products into a singular method of treatment (also see MPEP 2144.06(I) - In re Kerkhoven – cited in art rejections below). Further, it provides a framework under which it would be obvious to try the specified combination of products in a singular method (MPEP 2143(I)E).
Regarding 3), per MPEP 2143.02(I): Where there is a reason to modify or combine the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success.
As it is obvious to combine multiple compositions useful for the same purpose – in this case, combine multiple therapeutics all used to treat cancer into a method of treating cancer – a reasonable expectation of success has been established.
Regarding 4), per MPEP 716.02(b)(I): “The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992).” In the instant application, none of the data put forth demonstrate statistical significance, including Example 13/Figure 30 and S1-S5, as cited in arguments. Thus, this requirement has not been met.
Moreover, MPEP 716.02(d) requires that unexpected results be commensurate in scope with the claimed invention: “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range.”
The claims of the instant application are drawn to a method treating cancerous solid tumors in a subject by administering a first, second, and third composition comprising FLT3, IFNg, and SEQ ID NO: 9, respectively. The data in the instant application demonstrate that said combination is effective at treating certain types of solid tumors: colon, breast, lung, melanoma, and prostate (Figures S1-S5 in Remarks). However, the data does not support unexpected results commensurate in scope with the claimed invention as it unclear if all species of solid tumors can be treated by this method; see scope of enablement rejection, below.
Although in some instances unexpected results of a species may be sufficient to overcome an obviousness rejection so long as one skilled in the art could reasonably determine a trend in the exemplified data that would allow them to extrapolate the results (see MPEP 716.02(d)(I)), in the instant case there is no throughline or trend that one skilled in the art would be able to reasonably use to extrapolate therefrom.
Collectively, the arguments set forth in 1)-4) above are insufficient to overcome the outstanding obviousness rejection, which has been maintained/modified herein.
Consequently, the double patenting rejections have also been modified/maintained herein.
Claim Status
Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are pending under examination. Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, and 35 are currently amended. Claims 38-43 are new.
Priority
This application is the 371 national stage entry of PCT/SG2020/050344, filed 6/22/2020. The priority date of 6/22/2020 is acknowledged.
Information Disclosure Statement
The IDS submitted on 2/20/2026 is under consideration.
New - Claim Objections
Claim 13 is objected to because of the following informalities: lines 1-2 recite “comprising comprising”. Appropriate correction is required.
Claim Interpretation
Claim 26 recites that the INFg reprograms a M2 TAM into an M1 TAM, wherein the reprogramming results in a surface marker expression change. Because this is a functional outcome resulting from administration of INFg, the claim is being interpreted based upon the structural limitations of the claim (administration of INFg).
New - 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.
Claim 42 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 42 recites the broad recitation “at least 5 times”, and the claim also recites “at least 4 times,” “at least 3 times,” “at least 2 times,” and “at least 1 time” which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Additionally, claim 42 recites the limitation "the sixth infusion" in line 5. There is insufficient antecedent basis for this limitation in the claim as there is no prior recitation of an infusion, let alone a sixth infusion.
Claim 42 is further rejected for being indefinite based upon the “and/or” limitation. Specifically, the scope of (a) and (b) appear to contradict each other as (b) requires at least a second repetition of steps i)-iv), which is not possible if in (a) the steps are repeated only once. Further, (b) recites that the at least second repetition of steps i)-iv) begins about 16 days after the sixth infusion of the fourth composition, but repeating steps i)-iv) for a second time would have only resulted in two prior administrations of the fourth composition (the first initial administration, as recited in claim 13, and the first repetition), and, thus, is not possible. For these reasons, claim 42 is rejected.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Written description rejection
Claims 5, 13, 31, and 40-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The above claims recite that administration of a composition comprising an anti-PD1 antibody, which recites a feature by functional rather than structural language. There is nothing further in the claim to indicate the structural feature(s) required to meet this functional limitation, and describing an invention by function is insufficient to meet the written description requirement.
Per MPEP 2163(II)(3)(a), disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties).
There are several different anti-PD-1 antibodies, such as nivolumab, BMS-39886, pembrolizumab, pidilizumab, cemiplimab, dostarlimab, and retifanlimab (see Table 1 of 1) Javed et al., 2024, Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges. Front. Immunol. 15:1383456; and 2) Naidoo et al., 2015, Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies, Annals of Oncology, 26, 2375-2391.); and each of these antibodies has its own unique paratope that recognizes a unique epitope on PD-1 (Fessas et al. A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol. 2017 Apr;44(2):136-140.). Based on the lack of structural limitations recited, any of these would meet the limitations of the instant claims. Additionally, the examples recited above only contemplate antibodies for treating humans; however, the claims recite that a subject is administered such antibodies, wherein a subject is inclusive of any mammal. Liu teaches treating mice with PD-1 blocking antibodies, which would also meet the limitations of the above claims (Liu et al. Identification of anti-mouse PD-1 agonist antibodies that inhibit T cell activation. Front Immunol. 2025 Sep 23;16:1631929.).
Applicants have cemiplimab (Libtayo), nivolumab (Opdivo), pembrolizumab (Keytruda) as anti-PD1 antibodies ([0171]). However, the claims listed above are written such that they contemplate or include additional compounds that retain the same functional characteristics beyond these examples in the specification. Thus, the instant specification does not provide adequate written description to possess the broad genera described above.
Scope of enablement rejection
Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, 38-43 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a subset of solid tumors, does not reasonably provide enablement for treating all solid tumors broadly. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Applicant’s attention is drawn to In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) The nature of the invention; 2) the state of the prior art; 3) the relative skill of those in the art; 4) the predictability or unpredictability of the art; 5) the breadth of the claims; 6) the amount of direction or guidance presented; 7) the presence or absence of working examples; and 8) the quantity of experimentation necessary.
1) Nature of the invention and 5) breadth of the claims: The claims are drawn to a
method of treating cancerous solid tumors in a subject in need thereof comprising administering a first composition comprising FLT3, a second composition comprising INFg, and a third composition comprising SEQ ID NO: 9 as a recombinant polypeptide or nucleic acid sequence encoding said polypeptide. In some instances, the method of treatment also includes administering an anti-PD-1 antibody and/or TNFa receptor.
2) State of the prior art and 4) predictability or unpredictability of the art: The art at the
time of filing indicated a variety of tumors release damage-associated molecular patterns (DAMPs) in response to different modes and stages of cell death (see, for instance, Table 1 of Hernandez, Pg 23-24; Hernandez C, Huebener P, Schwabe RF. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene. 2016 Nov 17;35(46):5931-5941.). Beyond calreticulin, HSP70, and HSP90, the three major DAMPs discussed in the instant specification that increase in certain cancer cells in response to treatment with SEQ ID NO: 9 (see instant [0003] and Figures 3-14), there are several other DAMPs that tumor cells can release or express. For instance, adenosine is released by glioblastoma multiforme and HMGB1 is released by glioma (Hernandez, Table 1; Pg 5935, left column, “HMGB1”). Without a clear connection to calreticulin, HSP70, and HSP90, will the instantly claimed method be able to treat these types of solid tumors?
According to Hernandez, the mode of cell death determines the spectrum and activity of the DAMPs released. Additionally, cancer cells can also release DAMPs through stress pathways that either precede or are not directly related to cell death. This suggest that targeting calreticulin, HSP70, and HSP90, as intended by the claims, may be insufficient to effectively treat any and all types of solid tumors as each cancer cell likely releases or expresses its own set of DAMPs depending on the context (Pg 2-4, “1. Release of DAMPs in tumors or their environments”).
In some cases, DAMPs may also promote tumor viability rather than tumor destruction. According to Roh et al., DAMPs may mediate tumor progression by inducing chronic inflammation; HSPs, among others, activate inflammatory pathways and release IL-1, IL-6, LT-β, INFγ, TNF, and TGF-β (Roh JS, Sohn DH. Damage-Associated Molecular Patterns in Inflammatory Diseases. Immune Netw. 2018 Aug 13;18(4):e27.; Pg 7, “DAMPS in cancer”). Further, according to Songjang et al., in situations where drugs induce immunogenic cell death, the outcome may be impacted by the ratio between immunostimulatory and immunoinhibitory DAMPs, with some tumor-derived DAMPs activating tumor-expressed TLRs to promote tumor cell motility, invasion, metastatic spread, and chemotherapeutic-resistance. Cisplatin and oxaliplatin induced DAMP release from cholangiocarcinoma cells (which includes HSP family proteins and calreticulin) promotes tumor activities instead of inhibiting them (Songjang W, Nensat C, Nernpermpisooth N, Seenak P, Pankhong P, Jumroon N, Kumphune S, Jiraviriyakul A. Tumor-Promoting Activity and Proteomic Profiling of Cisplatin/Oxaliplatin-Derived DAMPs in Cholangiocarcinoma Cells. Int J Mol Sci. 2022 Sep 11;23(18):10540.; Abstract, Pg 3, “2.2 Cisplatin and oxaliplatin induced DAMP expression in CAA cells” – Pg 7, “2.4 Chemo-drug-derived DAMPs activated the pro-survival signal of CAA cells”).
Given that DAMPs, including calreticulin, HSP70, and HSP90, can be cancer cell-type
specific, and, in some cases, have tumor promoting capabilities rather than tumor inhibiting capabilities, it is unpredictable whether the claimed method could effectively treat all types of cancerous solid tumors. Applicants have demonstrated that a subset of solid tumors can effectively be targeted by such a method (more below), but this is not comprehensive of solid tumors as a genus.
3) The relative skill of those in the art: The relative skill of those in the art is high.
6) The amount of direction or guidance presented: At the time of filing, no direction or
guidance was presented in either the prior art or the instant specification that would enable one to sequentially administer the above compositions to treat solid tumors as broadly as intended by the claims.
7) The presence or absence of working examples: The instant specification
demonstrates that the invention is capable of treating breast, lung, prostate, and colon cancer as well as melanoma (see Examples 2, 4, 11, and 12).
8) The quantity of experimentation necessary: One skilled in the art would be burdened
with undue experimentation to determine the precise parameters and conditions necessary to effectively treat all types of cancerous solid tumors through sequential administration of the above recited compositions.
Therefore, in view of the Wands factors, as discussed above, Applicants fail to provide information sufficient to practice the claimed invention broadly treating all solid tumors.
Maintained/Modified - 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 (i.e., changing from AIA to pre-AIA ) 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 10,150,801 B1, published 11/12/2018) in view of Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019) and Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.).
Chen teaches recombinant polypeptides, nucleic acids encoding recombinant polypeptides, and methods for using thereof. The methods include treating a cell proliferative disorder, such as cancer, specifically lung, colon, and breast cancer (solid tumor), by administering the polypeptides and/or nucleic acids (Abstract; Col. 3, lines 24-26). One of the peptides taught by Chen is SEQ ID NO: 9, which is identical to the instant SEQ ID NO: 9 (Sequence Listing, Col. 65 – 67).
Chen does not teach a method of treating cancer comprising administering a composition with said SEQ ID NO: 9 after a first composition is administered comprising FLT3 and a second composition is administered comprising INFg.
Najibi teaches vaccine compositions and methods to treat a variety of cancers (Abstract). The method includes administering to the subject a vaccine composition, wherein the vaccine composition comprises a porous scaffold and a recruitment composition, that recruits an immune cell to the scaffold, and administering to the subject an agent that induces an immunogenic cell death, thereby treating cancer ([0007]). The types of cancers that can be treated include breast cancer, colon cancer, and lung cancer among others ([0021]). The recruitment composition comprises a growth factor or cytokine, such as FMS-like tyrosine kinase 3 ligand (FLT3L) ([0029, 0052, 00343]). Cytokines that can be administered include INFg ([00343]).
Le Tourneau teaches dosage optimization in phase I cancer clinical trials (Title, Abstract). Le Tourneau explains that in rule-based phase I trials of drug combinations, the dose level of each drug may be based on several factors such as preclinical data, current tumor-specific standard treatments, the expected control arm if the combination of drugs under evaluation may be benchmarked by future randomized trials, and/or empiricism (Pg 715, “Designs for trials of combinations of agents, second paragraph). Bayesian modeling as well as pharmacokinetic analyses may further provide information regarding toxicities and interactions between different anticancer drugs administered in combination (third and fourth paragraphs). All of these decisions impact the recommended schedules and dosages, which can determine the success or failure of a combination.
Thus, regarding claim 2, Chen teaches a method of treating cancer, including breast, lung, and colon cancer, by administering the instant SEQ ID NO: 9, either as a recombinant polypeptide or as a nucleic acid encoding said polypeptide. Najibi teaches methods of treating cancer via cancer vaccines comprising FLT3L and recruitment compositions comprising cytokines such as INFg, which can also be used to treat breast, lung, and colon cancer. Therefore, it would be prima facie obvious to combine the FLT3L and INFg compositions taught by Najibi to the method of treating cancer using SEQ ID NO: 9 taught by Chen to further improve treatment by combining multiple therapeutics useful for the same purpose. One skilled in the art would have a reasonable expectation of success because all of the compositions had been used to treat the same types of cancers.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See MPEP 2144.06(I).
Although Chen and Najibi do not explicitly teach the schedule (order of administration of the compositions) claimed, it would have been prima facie obvious to one of ordinary skill in the art to optimize because Le Tourneau recognized that the scheduling of combinations of anticancer therapeutics depended on a number of factors, as described above. Thus, it would have been obvious to optimize the schedule (order of administration) in order to effectively treat cancer. See MPEP 2144.05(II).
Regarding claim 5, Najibi teaches administering a composition comprising an anti-PD-1 antibody ([0014, 00440, 00444]).
Regarding claim 7, Najibi teaches that the vaccine composition, described above, may be administered 1 day (24 hours) prior to the administration of the inhibitor of immunosuppression (i.e., an anti-PD-1 antibody, a subsequent composition; [0014]).
Regarding claim 13, Chen and Najibi do not explicitly teach administering the above compositions multiple times. However, one skilled in the art would recognize the potential need to repeat the therapeutic regimen, depending on the type of cancer and its severity. Therefore, it would be obvious to repeat the above recited steps at least once.
Regarding claims 8, 10, 12, 25, 31, and 33, as stated above, although Chen and Najibi do not explicitly teach the schedules or dosages claimed, it would have been prima facie obvious to one of ordinary skill in the art because Le Tourneau recognized that scheduling and dosing of combinations of anticancer therapeutics depended on a number of factors, as described above. Thus, it would have been obvious to optimize the order of administration dosage schedule (claims 8, 10, 12), and dosages (claims 25, 31, and 33) as claimed in order to effectively treat cancer. See MPEP 2144.05(II).
Regarding claims 26, Najibi teaches the vaccine composition can include INFg. The instant specification indicates that IFNg is an IL-10 inhibitor that reprograms M2 TAM to M1 TAM ([0169]).
Regarding claim 32, Najibi teaches establishing 4T1 tumors (solid tumor) in Balb/c mice by subcutaneous injection, wherein after 5 or 6 days the tumors reached a diameter of 6-7mm (0.6-0.7cm) ([00502, 00504]) or after 9 days the tumors reached a diameter of ~10-12mm (1.0-1.2cm) ([00505]); the tumors are then subsequently treated.
Regarding claim 35, Najibi teaches that the vaccine composition can be administered intravenously ([0018]).
Regarding claim 43, Najibi teaches anti-PD-1 antibodies such as nivolumab and pembrolizumab ([00440 and 00444]).
Claim(s) 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 10,150,801 B1, published 11/12/2018), Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019), and Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.), as applied to claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 43 above, and further in view of Sims (US20010053764 A1, published 12/20/2001, cited on IDS filed 11/27/2024).
The teachings of Chen, Najibi, and Le Tourneau have been set forth above. Najibi teaches that the vaccine composition, described above, can be administered subsequently or concurrently with other cancer therapies (chemotherapy, e.g., administration of an agent that induces immunogenic cell death; [00243]). Chen, Najibi, and Le Tourneau do not teach a method comprising administering a fourth composition comprising TNFa receptor.
Sims teaches methods treating cancer with IL-1 inhibitors, compositions, or combination therapies ([0045]). Cytokine inhibitors can be used in combination with type II IL-1 receptors such as those that antagonize TNF, particularly TNFa ([0026]). TNFa antagonists include recombinant proteins comprising all or portions of the receptors for TNFa ([0028]); said TNFa inhibitor can be used in combination with soluble type II IL-1 receptor to treat cancers such as lung, colon and breast cancer ([0045]).
Thus, regarding claims 38 and 40, Chen, Najibi, and Le Tourneau teach administration of a first composition comprising FLT3, followed by a second composition comprising INFg, followed by a third composition comprising SEQ ID NO: 9, to treat solid tumors such as breast, lung, and colon cancer; additional combination therapies can be administered concurrently or subsequent to administration of the described compositions, per Najibi. Sims teaches treating breast, lung, and colon cancer with the TNFa receptor as part of combination therapy. Therefore, it would be prima facie obvious to administer a composition comprising the TNFa receptor, concurrent with or subsequent to administration of the third composition, to further improve treatment by combining multiple therapeutics useful for the same purpose. One skilled in the art would have a reasonable expectation of success because all of the compositions had been used to treat the same types of cancers.
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See MPEP 2144.06(I).
Regarding claims 39 and 41-42, as stated above, although Chen, Najibi, and Sims do not explicitly teach the schedules or dosages claimed, it would have been prima facie obvious to one of ordinary skill in the art because Le Tourneau recognized that scheduling and dosing of combinations of anticancer therapeutics depended on a number of factors, as described above. Thus, it would have been obvious to optimize the order of administration dosage schedule (claim 42) and dosages (claims 39 and 41) as claimed in order to effectively treat cancer. See MPEP 2144.05(II).
Maintained/Modified - 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,150,801 B1 (‘801) in view of Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019), Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.), and Sims (US20010053764 A1, published 12/20/2001, cited on IDS filed 11/27/2024).
Claim 1 of US ‘801 recites a recombinant polypeptide comprising an amino acid sequence of SEQ ID NO: 9. SEQ ID NO: 9 of US ‘801 and the instant SEQ ID NO: 9 are identical. US ‘801 discloses that SEQ ID NO: 9 can be used to treat cancer.
Dependent claims further include a pharmaceutical compositions (claims 2 and 3).
US ‘801 does not teach a method of treating cancer comprising first administering a composition comprising FLT3, followed by administration of a second composition comprising INFg, followed by a third composition comprising SEQ ID NO: 9.
Najibi teaches vaccine compositions and methods to treat cancer. The method includes administering to the subject a vaccine composition, wherein the vaccine composition comprises FLT3L, and a recruitment composition, wherein the recruitment composition comprises INFg; anti-PD-1 antibody inhibitors can also be administered in combination. Le Tourneau teaches optimization of drug combinations in clinical trials. Sims further teaches methods treating cancer with combination therapies that include TNFa receptor.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Najibi, Le Tourneau, and Sims into US ‘801, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Najibi, Le Tourneau, and Sims teach using combinations of different therapeutics to treat cancer. Thus, the claims are obvious in view of US ‘801.
Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 10,351,607 B1 (‘607) in view of Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019), Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.), and Sims (US20010053764 A1, published 12/20/2001, cited on IDS filed 11/27/2024).
Claim 1 of US ‘607 recites a nucleic acid encoding a recombinant polypeptide comprising an amino acid sequence of SEQ ID NO: 9. SEQ ID NO: 9 of US ‘607 and the instant SEQ ID NO: 9 are identical. US ‘607 discloses that SEQ ID NO: 9 can be used to treat cancer.
Dependent claims further include an expression vector comprising the nucleic acid sequence (claim 2).
US ‘607 does not teach a method of treating cancer comprising first administering a composition comprising FLT3, followed by administration of a second composition comprising INFg, followed by a third composition comprising SEQ ID NO: 9.
Najibi teaches vaccine compositions and methods to treat cancer. The method includes administering to the subject a vaccine composition, wherein the vaccine composition comprises FLT3L, and a recruitment composition, wherein the recruitment composition comprises INFg; anti-PD-1 antibody inhibitors can also be administered in combination. Le Tourneau teaches optimization of drug combinations in clinical trials. Sims further teaches methods treating cancer with combination therapies that include TNFa receptor.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Najibi, Le Tourneau, and Sims into US ‘607, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Najibi, Le Tourneau, and Sims teach using combinations of different therapeutics to treat cancer. Thus, the claims are obvious in view of US ‘607.
Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10,301,364 B1 (‘364) in view of Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019), Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.), and Sims (US20010053764 A1, published 12/20/2001, cited on IDS filed 11/27/2024).
Claim 1 of US ‘364 recites a method of enhancing or inducing an immune response against a cancer cell in a subject in need thereof comprising administering to said subject the recombinant polypeptide SEQ ID NO: 9. SEQ ID NO: 9 of US ‘364 and the instant SEQ ID NO: 9 are identical. Claim 7 further recites a method of enhancing or inducing the endogenous presentation of disease associated antigens on the surface of a cancer cell in a subject in need thereof, comprising administering to said subject the recombinant polypeptide of SEQ ID NO: 9. Claim 10 also recite a method of treating or alleviating at least one of the symptoms of cancer in subject in need thereof comprising administering to said subject a therapeutically effective amount of the recombinant polypeptide of SEQ ID NO: 9.
Dependent claims further include the immune response comprises immunogenic cell death of the cancer cell (claim 2), the immunogenic cell death comprises endogenous dendritic cell activation or an increase in DAMP signals (claims 3 and 4), administering SEQ ID NO: 9 with a pharmaceutically acceptable carrier (claims 5, 6, 8, 9, 11, 12).
US ‘364 does not teach a method of treating cancer comprising first administering a composition comprising FLT3, followed by administration of a second composition comprising INFg, followed by a third composition comprising SEQ ID NO: 9.
Najibi teaches vaccine compositions and methods to treat cancer. The method includes administering to the subject a vaccine composition, wherein the vaccine composition comprises FLT3L, and a recruitment composition, wherein the recruitment composition comprises INFg; anti-PD-1 antibody inhibitors can also be administered in combination. Le Tourneau teaches optimization of drug combinations in clinical trials. Sims further teaches methods treating cancer with combination therapies that include TNFa receptor.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Najibi, Le Tourneau, and Sims into US ‘364, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Najibi, Le Tourneau, and Sims teach using combinations of different therapeutics to treat cancer. Thus, the claims are obvious in view of US ‘364.
Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,675,332 B1 (‘332) in view of Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019), Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.), and Sims (US20010053764 A1, published 12/20/2001, cited on IDS filed 11/27/2024).
Claim 1 of US ‘332 recites a method of treating cancer in a subject in need thereof comprising: a) administering a first amount of an agent that reduces IL-10 to the subject; b) administering a first amount of a recombinant polypeptide comprising an amino acid sequence having at least 99% sequence identity to the polypeptide of SEQ ID NO: 9 or a nucleic acid encoding the recombinant polypeptide comprising an amino acid sequence having at least 99% sequence identity to the polypeptide of SEQ ID NO: 9 to the subject between 2-24 hours after the administration of the first amount of the agent; and c) administering a second amount of the recombinant polypeptide or the nucleic acid to the subject at least 20 hours after the administration of the first amount of the recombinant polypeptide or the nucleic acid. SEQ ID NO: 9 of US ‘332 and the instant SEQ ID NO: 9 are identical. Claim 27 further recites a method of treating cancer in a subject comprising: a) administering a first amount of a recombinant polypeptide comprising an amino acid sequence having at least 99% sequence identity to the polypeptide of SEQ ID NO: 9 or a nucleic acid encoding the recombinant polypeptide comprising an amino acid sequence having at least 99% sequence identity to the polypeptide of SEQ ID NO: 9 to the subject; and b) administering a second amount of the recombinant polypeptide or the nucleic acid to the subject at least 20 hours after the administration of the first amount of the recombinant polypeptide or the nucleic acid.
Dependent claims further include the relative timings of the administrations (claims 2-6), dosages (claims 7-12, 15-20, 26), mode of administration (claims 13-14), the IL-10 reducing agent (claims 22-23), the cancer (claims 24-25), the amino acid or nucleic acid sequence comprises SEQ ID NO: 9 (claims 21 and 28).
US ‘332 does not teach a method of treating cancer comprising first administering a composition comprising FLT3 prior to administration of the composition comprising INFg, followed by a composition comprising SEQ ID NO: 9.
Najibi teaches vaccine compositions and methods to treat cancer. The method includes administering to the subject a vaccine composition, wherein the vaccine composition comprises FLT3L, and a recruitment composition, wherein the recruitment composition comprises INFg; anti-PD-1 antibody inhibitors can also be administered in combination. Le Tourneau teaches optimization of drug combinations in clinical trials. Sims further teaches methods treating cancer with combination therapies that include TNFa receptor.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Najibi, Le Tourneau, and Sims into US ‘332, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Najibi, Le Tourneau, and Sims teach using combinations of different therapeutics to treat cancer. Thus, the claims are obvious in view of US ‘332.
Claims 2, 5, 7-8, 10, 12-13, 25-26, 31-33, 35, and 38-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-11 of copending Application No. 19/082,728 (‘728 reference application; claim set filed 3/18/2025) in view of Najibi et al. (WO 2021061837 A1, effectively filed 9/23/2019), Le Tourneau et al. (Dose escalation methods in phase I cancer clinical trials. J Natl Cancer Inst. 2009 May 20;101(10):708-20.), and Sims (US20010053764 A1, published 12/20/2001, cited on IDS filed 11/27/2024).
Claim 1 of copending Application No. ‘728 recites a nucleic acid encoding a recombinant polypeptide comprising an amino acid sequence having at least 99% sequence identity to the recombinant polypeptide of SEQ ID NO: 9. SEQ ID NO: 9 of copending Application No. ‘728 and the instant SEQ ID NO: 9 are identical.
Dependent claims include an expression vector or recombinant peptide (claims 2 and 3), a pharmaceutical composition (claims 4 and 5), a method of enhancing or inducing an immune response against a cancer cell (claims 6 and 7), a method of enhancing or inducing the endogenous presentation of disease associated antigens on the surface of a cancer cell in a subject in need thereof (claims 8 and 9), and a method of treating, preventing, or alleviating at least one of the symptoms of cancer in a subject in need (claims 10 and 11).
Copending Application No. ‘728 does not teach a method of treating cancer comprising first administering a composition comprising FLT3, followed by administration of a second composition comprising INFg, followed by a third composition comprising SEQ ID NO: 9.
Najibi teaches vaccine compositions and methods to treat cancer. The method includes administering to the subject a vaccine composition, wherein the vaccine composition comprises FLT3L, and a recruitment composition, wherein the recruitment composition comprises INFg; anti-PD-1 antibody inhibitors can also be administered in combination. Le Tourneau teaches optimization of drug combinations in clinical trials. Sims further teaches methods treating cancer with combination therapies that include TNFa receptor.
Therefore, it would be prima facie obvious to one of ordinary skill in the art to incorporate the teachings of Najibi, Le Tourneau, and Sims into copending Application No. ‘728, thereby arriving at the instant invention. One skilled in the art would have a reasonable expectation of success as Najibi, Le Tourneau, and Sims teach using combinations of different therapeutics to treat cancer. Thus, the claims are obvious in view of copending Application No. ‘728.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Prior Art Cited but not Referenced
US 10,301,364 B1 (filed 9/21/2018, published 5/28/2019) and US 10,351,607 B1 (filed 9/21/2018, published 7/16/2019) both teach the instant recombinant protein SEQ ID NO: 9, and a nucleic acid encoding thereof, as well as methods for treating a proliferative cell disorder, such as cancer by administering the disclosed protein and/or nucleic acid to a subject in need.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/SARA E KONOPELSKI SNAVELY/Examiner, Art Unit 1658
/FRED H REYNOLDS/Primary Examiner, Art Unit 1658
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