palmDETAILED 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 .
Election/Restrictions
Applicant’s election without traverse of group I, claims 3-8, 36-40, 106-108, 123-124 and species the combination of peptide, polysaccharides, proteins ; polyphenols, curcumin, demothoxycurcumin, and bisdemethoxycurcumin, and terpenoid, ar-turmerone, a-turmerone, and b-turmerone and PTTG1 in the reply filed on 01/15/2026 is acknowledged.
Claim 36 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/15/2026.
Claims 3-8, 37-40, 47, 106-108, 123-124 is under examination with respect to PTTG1 and the combination of peptide, polysaccharides, proteins ; polyphenols, curcumin, demothoxycurcumin, and bisdemethoxycurcumin, and terpenoid, ar-turmerone, a-turmerone, and b-turmerone.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/848194, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The claims require treating a patient with head and neck cancer comprising administering a polypharmaceutical composition comprising high polarity compounds comprising peptides, polysaccharides, and proteins, medium polarity compounds comprising polyphenols, curcumin, demethoxycurcumin, and bisdemethoxycurcumin, and non-polar compounds comprising terpenoids, ar-turmerone, a-turmerone, and b-turmerone isolated from Curcuma longa. The claims further comprise measuring PTTG1. Additional claims require evaluating a response to a cancer therapy by measuring a level of PTTG1 in a sample. While ‘194 provides support for apigenin derivative, flavonoid derivative, and APG-157 (originally filed claims) and provides support for treating patients with APG-157, ‘194 does not provide support for the genus of polypharmaceutical composition isolated from Curcuma longa as required in claims 1-8, 36-40, and 47. Additionally ‘194 does not provide support for determining response to a cancer therapy by measuring a level of PTTG1. While ‘194 provides method for measuring expression of PTTG1 before and after administering an apigenin derivative, specifically APG-157, ‘194 does not provide support for the genus of any cancer or any cancer treatment as encompassed by claims 106-108 and 123-124. As such the priority date for the instant claims is 05/15/2020.
Claim Objections
Claims 3, 8, 37-39, and 47 are objected to because of the following informalities: the claims are not grammatically correct. The claims are missing commas in the preamble of claim 1 and after the claim number in claims 8, 37-39, and 47 . Appropriate correction is required.
Claim 3 is objected to because of the following informalities: Curcuma longa should be italicized. Appropriate correction is required.
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.
Claims 8, 37-40, 47 and 123-124 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.
Claims 8, 37-39 and 47 recite “The method of claim 3 any of claims 3-7”,“The method of claim 3 any of claims 3-35”, “The method of claim 3 any of claims 3-36”, “The method of claim 3 any of claims 3-37”, “The method of claim 39 any of claims 39-46”. These recitations render the claim indefinite. It is unclear if the claim requires the method of claim 3 or if the claim is requiring any of the claims 3-35, 3-36, 3-37 or 39-46. The metes and bound of the claim limitations are unclear. Additionally claims 37-39 and 47 are incomplete claims because each of the claims depend from canceled claims. Specifically for claims 37-39, claims 9-35 are canceled and for claim 47, claims 41-46 are canceled. Claim 40 depends from claim 39 and is indefinite for the reasons applied to claim 39.
Claim 123 recites “the method of claim 106 any of claims 106-122”. This recitation renders the claim indefinite. It is unclear if the claim requires the method of claim 106 or any of claims 106-122. If the claim requires any of claims 106-122, the claim is incomplete as claims 109-122 are canceled. Claim 124 is indefinite depending from claim 123 for the reasons applied to claim 123.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 106-108 and 123-124 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract idea and law of nature without significantly more.
Claim 106 recites a method for evaluating response to a cancer therapy. Claim 123 recites comparing the level of expression to a control level of expression. These steps encompass an abstract idea that is a mental process, evaluating response to a therapy and comparing expression to a control level. Each of these steps of evaluating and comparing are mental processes. Neither the specification nor the claims set forth limiting definition for evaluating or comparing, the claims do not set forth how each step is accomplished and the broadest reasonably interpretation is a step that can be accomplished mentally be evaluating data and critical thinking process such that one mentally reads information regarding expression of PTTG1 then draws a mental conclusion. Such evaluating and comparing encompass process that may be performed mentally and this is an abstract idea.
The claims recite a law of nature/natural phenomenon. Claim 106 recites evaluating response to a cancer therapy by measuring expression of PTTG1. The recited relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of a natural process.
This judicial exception is not integrated into a practical application because the claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application. The steps in addition to the judicial exception are data gathering steps that do not apply or integrate the judicial exception in any way. The claims do not include elements that are sufficient to amount to significantly more than the judicial except because the steps in addition to the judicial exception are data gathering steps recited at a high level of generality employing techniques that were well established, routine and conventional at the time of the invention. The courts have recognized that measuring expression is among the well-understood, routine and conventional activity in the life sciences arts when claimed in a merely generic matter. Prior to the invention, X taught measuring PTTG1 expression in cancer samples. This evidences that these steps were conventional at the time of the invention.
Claim 107 and 108 limit the biological sample, thus a field of use limitation which does not amount to significantly more than the judicial exception. Additionally it was routine and convention to assay expression in cfDNA and tissue samples as taught by X.
Claims 123-124 adds additional steps to the data analysis which is an additional judicial exception since the comparing could be carried out in the mind.
Claim Rejections - 35 USC § 112
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.
Claims 3-8, 37-40, 47, 106-108, 123-124 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 a method of treating a subject with OSCC cancer by administering APG-157 and measuring expression levels of PTGG1, does not reasonably provide enablement for a method of determining cancer therapy response or a method of treating a patient with head and neck cancer by administering a polypharmaceutical composition and measuring a level of expression of PTTG1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Nature of the invention and breadth of the claims
The claimed methods are drawn to treating a patient with head and neck cancer comprising administering to the patient a polypharmaceutical compositions comprising high polarity compounds, medium polarity compounds, and non-polar compounds isolated from Curcuma longa, wherein the composition is administered after a biological sample from the patient is measured for a first level of PTTG1.
The claims encompass treatment of any head and neck cancer. The claims generically encompass any level of PTTG1 measured and any polypharmaceutical composition with the claimed compounds and ratio isolated from Curcmina longa.
Additional claims encompass evaluating any response to any cancer therapy by measuring any level, increase or decrease, of PTTG1 from any sample including tissue or plasma sample.
The claims thus require knowledge of reliable and robust association between the expression of PTTG1 and response to cancer therapy. Additionally, the claims require knowledge of any polypharmaceutical composition as claimed for treating head and neck cancer.
Direction provided by the specification and working example
The instant specification provides an example wherein samples from human subjects with oral squamous cell carcinoma (OSCC) patients were treated with APG-157 and were analyzed to determine expression of PTTG1. The specification provides data for 3 subjects with OSCC treated with APG-157 and measuring PTTG1 expression before and after treatment. The data in the specification comprises treating the patients with either 100mg or 200mg of APG-157 and measuring in plasma samples PTTG1 expression at 3 hours before treatment, 3 hours after treatment and 24 hours after treatment. Figure 5 demonstrates the expression values of PTTG1 of 3 patients treated with APG-157, 3 patients treated with a placebo and 3 healthy patients. The expression values vary dramatically among the patients treated. Patient 1 has a slight increase prior to treatment followed by increase after 3 hours and again after 24 hours whereas patient 2 has no expression measured prior to treatment, a very large increase in expression after 3 hours and a decreased expression after 24 hours and patient 3, similar to patient 1 has a slight increase in PTTG1 expression prior to treatment but then has a larger increase after 3 hours of treatment which is reduced after 24 hours of treatment. Each of the control groups have increased expression of PTTG1, similar to expression at different times points of the patients treated with APG157. Due to the varying expression levels of a limited population of subjects with no statistical analysis performed, it is cannot be concluded based on the data provided in the specification that expression of PTTG1 is related to response of treatment. None of the subjects are monitored over time to determine if the therapy is responsive. It is inconclusive based on the guidance in the specification if treatment of APG 157 was effective and which dosage of APG157 is effective and correlating this with PTTG1 expression. The specification provides no treatment with any other drug other than APG157 for OSSC.
Relevant to the breadth of the claims, there is no analysis of any non-human subjects. There is no analysis of any other therapy and any other cancer other than OSSC and APG157. The specification teaches only three subjects with OSSC treated with APG-157, treated with a placebo and healthy subjects with PTTG1 expression in plasma samples. There is no analysis of other therapies, cancers, or other biological samples.
State of the art, level of skill in the art, and level of unpredictability
While the state of the art and level of skill in the art with regard to measuring gene expression in human samples is high, the unpredictability in associating any particular expression with a specific phenotype, or identifying treatment response, as is encompassed by the claims, is even higher. The unpredictability is demonstrated by the related art and the instant specification.
Because the claims encompass and any subject organism, while the specification teaches only the analysis of human subjects, it is relevant to point out the unpredictability in extrapolating the gene expression, or its association with any phenotype, from one animal to any other different animal.
The claims encompass measuring PTTG1 expression in samples from subjects with cancer and specifically head and neck cancer. The claims encompass evaluating response to cancer therapy by measuring any level of PTTG1 expression. The specification asserts that increased expression of PTTG1 is correlated with treatment response, however the specification does not provide examples of different cancers with different treatment response and expression of PTTG1. The post filing art and prior demonstrate that overexpression of PTTG1 is associated with cancer and higher grade of cancer. The art demonstrates that a decrease in PTTG1 not an increase in associated with treatment response.
Xu (Oncology Letters, 15, 257-263, 2018) demonstrates that PTTG1 is overexpressed in lung cancer tissue (see fig 3). Ren (Biomedicine and Pharmacotherapy, 89, 2017, 108-115) teaches PTTG1 is overexpression in colorectal cancer and is an in dependent poor prognostic factor for colorectal cancer patients (see abstract).
Wang (Front. Bioscie (Landmark Ed) 2024, 29(2): 87) teaches PTTG1 is overexpressed in nearly all tumors, indicating promising prognostic and diagnostic capabilities (see abstract). Wang teaches PTTG1 is overexpression in various cancers and correlates with poor prognosis (see pg. 12, 2nd column). Wang does not teach that PTTG1 expression is correlated with therapy response.
Nakachi (Clin Transl Sci 2016, 9, 293-301) teaches PTTG1 expression response to aracatinib chemotherapy for ovarian cancer. Nakachi teaches sensitive cells had a reduction rate of PTTG1 expression while resistant cells had no change in expression of PTTG1 (see figure 4). Nakachi demonstrates that a decrease not an increase in expression of PTTG1 following treatment indicates a positive response to therapy.
Read (Cancer Res 78(20): 5863-76) teaches patients with high tumoral PTTG in HNSCC had the poorest overall survival. Read teaches PTTG expression in tumor tissue is upregulated in HNSCC (see elevated PTTG expression and phosphorylation). Read teaches overexpression of PTTG is associated with increased tumor invasiveness and cell migration in multiple settings. Read does not teach any expression of PTTG in response to treatment.
A review of PTTG1 in cancer biology by Rakoczy (Cells, 2025, 14, 330, p 1-24) teaches PTTG1 is a potential therapeutic target in various cancers and role as a biomarker. Rakoczy teaches PTTG1 overexpression in cancer and higher levels of expression of PTTG1 is correlated with higher histological grade of cancer. In breast cancer, Lin teaches suppressing PTTG1 may suppress breast cancer highlighting a potential therapeutic strategy involving PTTG1 suppression (see 3.5). Rakoczy teaches suppression of PTTG1 indicates therapeutic response and an increase in PTTG1 indicates higher grade of cancer.
Quantity of experimentation required
A large and prohibitive amount of experimentation would be required to make and use the claimed invention. Given that the claims generically encompass any cancer therapy with any cancer with any increase or decrease of PTTG1 to evaluate therapeutic response, one would have to perform large case: control studies, and validation of any results, to determine which therapies, cancers, and expression values may be reliably and robustly associated with therapeutic outcome. Additionally the claims encompass polypharmaceutical compositions derived from C. longa for treatment of head and neck cancer and measuring of PTTG1. One would have to perform large case: control studies and validation of a large genus of polypharmaceutical compositions to determine which compositions would treat HNC and how the expression of PTTG1 is related to therapy. Even for the particular distinct polypharmaceutical, APG157 disclosed in the specification, given the lack of statistically significant results with regard to the association of PTTG1 expression and therapeutic response of APG157, one would have to perform an analysis to see if expression of PTTG1 are robustly and reliably associated with therapeutic response.
Conclusion
Taking into consideration the factors outlined above, including the nature of the invention and breadth of the claims, the state of the art, the level of skill in the art and its high level of unpredictability, and the particular guidance in the specification including the examples, it is the conclusion that an undue amount of experimentation would be required to make and use the invention as claimed.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 106-108, 123-124 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (US20170073769A1).
Zhang teaches a method for predicting efficacy of a chemotherapy regimen in a subject. Zhang teaches the method comprising determining expression of PTGG1 and determining response to chemotherapy remine (see para 9). Zhang teaches determining expression from a sample, the sample includes plasma and tissue samples (see para 76) (claims 107-108). Zhang teaches comparing expression to a control group by applying a model to the expression of the biomolecules to predict probability of pathological complete response based on previously treated patients (see para 78) (claims 123-124).
The claims are enabled to the extent of the specification. In order to provide compost prosecution, Zhang has been provided as it teaches the positive active steps of the claims.
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.
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.
Claims 3, 6, 8, 37-40 are rejected under 35 U.S.C. 103 as being unpatentable over Mehta (WO2019195349A1, cited on IDS) in view of Read (Cancer Res, 2018, 78(2):5863-76)
Mehta teaches polypharmaceutical compositions that comprise high polarity compounds isolated from C. longa comprising peptides, polysaccharides, and proteins, medium polarity compounds comprising polyphenols, curcumin, demethoxycurcumin and bisdemethoxycurcumin, and non-polar compounds comprising terpenoid, ar-tumerone, a-tumerone, and b-tumerone with a ration of 1:1:1: to 3:6:1 by weight (see para 7). Mehta teaches methods of treating cancer by administering an effective amount of the polypharmaceutical composition. Mehta teaches the cancer is oral squamous cell carcinoma (see para 15) (claim 6, 8). Mehta teaches the composition is administered through oral mucosal route (see para 46) (claim 38). Mehta teaches administering AV1016 and measuring expression level of biomarkers (see para 113). Mehta teaches analysis of biopsy samples of expression before and after treatment with AV1016 (See para 42). Mehta does not teach measuring PTTG1 expression.
However Read teaches patients with HNSCC have a high PTTG and have the poorest overall survival (see abstract). Read teaches PTTG expression is significantly elevated in HNSCC patients (see elevated PTTG expression and phosphorylation).
Given the prior art teaches PTTG expression is elevated in HNSCC and is correlated with poorest survival, it would have been prima facie obvious to the ordinary artisan at the invention was made to include analysis of additional known biomarkers, including PTTG in the method of Mehta to all for a robust analysis of biomarkers with treatment of HNSCC. The skilled artisan would have been motivated to include analysis of PTTG expression before and after, including 7 days after administration of the polypharmaceutical compassion as taught by Mehta because Read teaches PTTG expression is correlated with poorest overall survival and Mehta suggests measuring biomarkers associated with cancer during treatment of OSCC with the claimed polypharmaceutical composition. Additionally the skilled artisan would have had a reasonable expectation of success of measuring PTTG expression before and after administration of polypharmaceutical of Mehta because Mehta teaches polypharmaceutical compositions for treatment of HNSCC and Read teaches PTTG is a biomarker for severity of HNSCC.
The claims are enabled to the extent of the specification. In order to provide compact prosecution, Mehta in view of Read has been provided as it renders obvious the positive active steps of the claims.
Claims 3-5, 8, 37-40 and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Mehta (WO2019195349A1, cited on IDS) in view of Fu (WO2019232485A1)
Mehta teaches polypharmaceutical compositions that comprise high polarity compounds isolated from C. longa comprising peptides, polysaccharides, and proteins, medium polarity compounds comprising polyphenols, curcumin, demethoxycurcumin and bisdemethoxycurcumin, and non-polar compounds comprising terpenoid, ar-tumerone, a-tumerone, and b-tumerone with a ratio of 1:1:1: to 3:6:1 by weight (see para 7). Mehta teaches methods of treating cancer by administering an effective amount of the polypharmaceutical composition. Mehta teaches the cancer is oral squamous cell carcinoma (see para 15) (claim 6, 8). Mehta teaches the composition is administered through oral mucosal route (see para 46) (claim 38). Mehta teaches administering AV1016 and measuring expression level of biomarkers (see para 113). Mehta teaches analysis of biopsy samples of expression before and after treatment with AV1016 (See para 42). Mehta does not teach measuring PTTG1 expression or measuring expression in cfRNA.
Fu teaches blood test to predict cancer incidence, recurrence, and monitor treatment. Fu teaches detecting amplification of PTTG1 using ctDNA in a blood test from a sample to determine cancer incidence and guide cancer treatment (see para 93).
It would have been prima facie obvious to the ordinary artisan at the invention was made to include analysis of additional known biomarkers, including PTTG1 in the method of Mehta to all for a robust analysis of biomarkers with treatment of HNSCC. The skilled artisan would have been motivated to include analysis of PTTG1 expression from blood samples using cfDNA before and after, including 7 days after administration of the polypharmaceutical composition as taught by Mehta because Fu teaches measuring amplification of PTTG1 in a blood sample from a patient for cancer prognosis and guide treatment allowing for a noninvasive method of analysis and Mehta suggests measuring biomarkers associated with cancer during treatment of OSCC with the claimed polypharmaceutical composition. Additionally the skilled artisan would have had a reasonable expectation of success of measuring PTTG expression from isolated ctDNA from a blood sample before and after administration of polypharmaceutical of Mehta because Mehta teaches polypharmaceutical compositions for treatment of HNSCC and Fu teaches an assay that allows for ease of monitoring treatment by analysis of cfDNA isolated from blood by analysis of known biomarkers, including PTTG 1.
The claims are enabled to the extent of the specification. In order to provide compact prosecution, Mehta in view of Fu has been provided as it renders obvious the positive active steps of the claims.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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, Fereydoun Sajjadi can be reached at 571-272-3311. 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.
/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
Prosecution Insights