DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ amendment and remarks, filed on 08/29/2025, in which claims 1 ,7, and 13 are amended.
Claims 1-18 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/CN2021/081377 filed on 03/17/2021, which claims domestic benefit to 62/990,650 filed on 03/17/2020.
Rejections Withdrawn
Applicant’s amendment and remarks, filed 08/29/2025, with respect that claims 1-18 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention has been fully considered and is persuasive, as claims 1-18 have been amended to clarify the scope of the claim such that the astragalus polysaccharides are defined. This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 08/29/2025, with respect that claims 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Xu in view of Gonzalez has been fully considered and is persuasive, the scope of the claims has been amended to limit that refined astragalus polysaccharides obtained by steps (a)-(f).
This rejection has been withdrawn.
The following are new grounds of rejection necessitated by Applicant’s amendment, in which claims 1, 7, and 13 are amended to recite refined astragalus polysaccharides obtained by steps (a)-(f).
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.
Claims 1, 3, 5-6, 13, and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (Med Oncol, 2012; PTO-892) in view of Chen et al. (US-20150290272-A1, 2015; PTO-892) and Gonzalez et al. (Nature, 2018; PTO-892 01/29/2025).
Guo discloses a trial which compares administration of an Astragalus polysaccharide (APS) injection integrated with vinorelbine and cisplatin (VC) to administration of VC alone for patients with advanced non-small-cell lung cancer (NSCLC) and discloses that the therapy comprising APS improved quality of life (abstract). Guo teaches that APS is a polysaccharide isolated from astragalus membranaceus, which is a commonly used herbal compound in traditional Chinese medicine, and that the APS was administered by injection, which is interpreted as a liquid (abstract). Guo teaches that after 3 cycles of treatment there were significant differences in the overall patient quality of life (P = 0.003), physical function (P = 0.01), fatigue (P<0.001), nausea and vomiting (P<0.001), pain (P = 0.007), and loss of appetite (P = 0.023) between the two study groups (abstract). One patient who received VC alone achieved a complete response compared with two patients on the VC-APS arm had a complete response, and 35% of patients on the VC arm had a partial response compared with 39% of patients on the VC-APS arm (paragraph bridging pages 1658-1659). Guo further teaches that, overall, 70.6% of patients on the VC-APS arm completed therapy as planned versus 63.2% of patients on the VC arm (page 1659, paragraph 1). Additionally, Guo teaches that a meta-analysis of 34 randomized controlled trials found that astragalus-based Chinese medicines may increase the effectiveness of platinum-based chemotherapy when combined with chemotherapy for patients with NSCLC (page 1660, paragraph 2). Guo discusses another study of patients with stage IIIB/IV NSCLC in which a daily injection of APS along with mitomycin C, vinblastine, and cisplatin (MVP) was compared to treatment with MVP alone and was found to provide a significantly higher response rate, survival rate and improved quality of life (paragraph bridging pages 1660-1661).
The teachings of Guo differ from that of the instantly claimed invention in that Guo does not teach that the astragalus polysaccharide was obtained by steps (a)-(f) of the instant claims or the administration of mannose (claims 1, 7, and 13) or the concentration of a composition comprising a refined astragalus polysaccharides and a mannose (claims 5, 12, and 18).
Chen discloses a pharmaceutical composition comprising an Astragalus membranaceus extract and pharmaceutically acceptable carrier, excipients or salts [0018]. The extract is comprised of polysaccharides [0040]. Chen teaches that, as a single medicinal material, the Astragalus extract has greater safety and lower side effects in clinical usage than herbal Chinese mixtures containing Astragalus [0015-0016]. Chen discloses a method for obtaining an Astragalus extract comprising mechanically processing Astragalus into chips [0022], putting the chips into an extract solution to extract at a temperature of 80-100 °C for 2-3 hours to obtain a first extract solution [0023], concentrating the first extract solution, then using ethanol or lower alkanol to precipitate and separate [0024]. The method further includes putting the selected precipitates though a centrifugation ultra filter and/or ion exchanger with a high molecular weight cut-off membrane [0025]. Chen provides further details to the method and teaches that, in some embodiments, the precipitation is done by first using a lower concentration of about 35-40% ethanol in a first precipitation step, and then using a higher concentration of about 65-80% ethanol in a second precipitation step. The concentrations of lower alkanol used in the precipitations can range from, among others, 80%-90% [0044]. Chen further indicates that the alkanol washes can be repeated for further purification and that precipitate samples are suspended in water for further processing [0045], which suggests that the precipitate samples are stirred during the alkanol wash steps. Chen further indicates that the crude extract of the alkanol extraction step may be dried using processes such as spray drying, vacuum drying, freeze-drying, critical point drying, solvent exchange, and the like, prior to the ultrafiltration step [0046].
Gonzalez teaches a method of treating cancer comprising administering the monosaccharide mannose, which causes growth retardation in several tumor types in vitro and enhances cell death in response to major forms of chemotherapy (page 719, paragraph 1). Gonzalez teaches that mannose has an anti-tumor effect against A549 cells (extended data figure 1). Mannose represents a well-tolerated means to interfere with glucose metabolism that could potentially be used clinically, either alone or in combination with other forms of cancer therapy (paragraph bridging pages 721-722). Administration of mannose had no negative effect on the health of test subjects (page 721, paragraph 3) and could be a simple, safe and selective therapy in the treatment of cancer (page 719, paragraph 1).
It would have been prima facia obvious before the effective filing date of the claimed invention to add the mannose of Gonzalez to the treatment of Guo to obtain the predictable result of a method of enhancing the treatment of lung cancer because Gonzalez teaches that mannose has an anti-tumor effect against a variety of cancers including lung cancer A549 cells and teaches that mannose has the potential to be used clinically in combination with other forms of cancer therapy, and Guo teaches that the combined therapy of astragalus polysaccharide injection integrated with vinorelbine and cisplatin offered improved quality of life for patients with advanced non-small-cell lung cancer. Furthermore, it would have been obvious to select astragalus polysaccharides derived by the method of Chen for administration in the treatment of Guo because Guo teaches that the astragalus polysaccharides are isolated from astragalus membranaceus, a commonly used herbal compound in traditional Chinese medicine, and Chen teaches that the Astragalus extract has greater safety and lower side effects in clinical usage than herbal mixtures containing Astragalus.
Regarding claims 5 and 18, Guo teaches that patients in the VC group received vinorelbine (20 mg/m2) on days 1, 8, and 15 while cisplatin (80 mg/m2) was administered on day 15. Patients in the VC-APS arm received 250 mg/days APS intravenously on day 1 through day 7 concurrently with a chemotherapy regimen identical to the VC arm. Treatment was modified in cases of hematological and/or non-hematological toxic effects that were evaluated on days 1 and 8 of each cycle in both arms. All dose adjustments were performed according to the system exhibiting the greatest degree of toxicity (page 1657, paragraph 5). Thus Guo teaches that the dosage and ratio of components of the cancer treatment is a result effective variable in terms of treatment toxicity such that one of ordinary skill in the art would have been motivated to optimize the concentration and ratios of the suggested composition comprising mannose and astragalus polysaccharides in order to achieve a treatment exhibiting low toxicity. MPEP 2144.05(II)(A) states that, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. Furthermore, MPEP 2144.05(II)(A) states that the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
Claims 2, 4, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (Med Oncol, 2012; PTO-892) in view of Chen et al. (US-20150290272-A1, 2015; PTO-892) and Gonzalez et al. (Nature, 2018; PTO-892 01/29/2025), as applied to claims 1 and 13, further in view of Sutiman et al. (PLOS ONE, 2016; PTO-892).
The combined teachings of Guo, Chen, and Gonzalez suggest the method of instant claims 1 and 13, as described in detail above.
The combined teachings of Guo, Chen, and Gonzalez differ from that of the instantly claimed invention in that they do not teach a method which includes treatment with a chemotherapy drug that is a targeted chemotherapy drug.
Sutiman discusses a study evaluation of the tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) (abstract). Sutiman teaches that vinorelbine alone or in combination with cisplatin only modestly improves survival, and more effective treatment approaches are clearly needed for the treatment of advanced NSCLC (page 2, paragraph 2). Sutiman discloses that treatment using the combination of erlotinib and oral vinorelbine is feasible and tolerable in patients with advanced NSCLC who had previously failed standard chemotherapy (page 12, paragraph 1). Sutiman teaches that, considering the safety and tolerability profile of the combination of oral vinorelbine and erlotinib shown in this study, further investigations are warranted to explore the clinical application of this combination (page 14, paragraph 2).
Thus one of ordinary skill in the art would have been motivated to administer a combination of the erlotinib of Sutiman and the combination of the method suggested by the combined teachings of Guo, Chen, and Gonzalez in a method of treating drug resistant cancer cells because Sutiman teaches that vinorelbine alone or in combination with cisplatin only modestly improves survival, and more effective treatment approaches are clearly needed for the treatment of advanced NSCLC and suggests combination with erlotinib as a treatment of NSCLC. One of ordinary skill in the art would have had a reasonable expectation of success because the combined teachings of Guo, Chen, and Gonzalez present a method of treating NSCLC and Sutiman teaches that treatment using the combination of erlotinib and oral vinorelbine is feasible and tolerable in patients with advanced NSCLC.
Claims 7, 10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al (Asian Pacific Journal of Cancer Prevention, 2013; PTO-892) in view of Guo et al. (Med Oncol, 2012; PTO-892), Chen et al. (US-20150290272-A1, 2015; PTO-892), and Gonzalez et al. (Nature, 2018; PTO-892 01/29/2025).
Zhou discusses effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549 cells (abstract) and the effect and mechanism of vinorelbine on reversing the multi-drug resistance (MDR) of lung cancer A549/DDP cells which are drug resistant cells that are resistant to cisplatin (page 4635, paragraph 2). Specifically, Zhou discloses that vinorelbine increased drug sensitivity to cisplatin (abstract). The toxic effect of vinorelbine on A549/DDP increases in a dose dependent manner and is able to enhance the sensitivity of lung cancer A549/DDP cells to cisplatin. (paragraph bridging pages 4636-4637) and vinorelbine inhibited the proliferation of A549/DDP cells (Figure 1). Zhou teaches that this study thus demonstrates that vinorelbine can effectively improve the sensitivity of cells to cisplatin and reverse the drug resistance (page 4638, paragraph 4) and provides experimental basis for the clinical applications in the field of multi-drug resistance reversal of lung tumor cells (page 4639, paragraph 1).
The teachings of Zhou differ from that of the instantly claimed invention in that Zhou does not teach administration of astragalus polysaccharides.
Guo discloses a trial which compares administration of an Astragalus polysaccharide (APS) injection integrated with vinorelbine and cisplatin (VC) to administration of VC alone for patients with advanced non-small-cell lung cancer (NSCLC) and discloses that the therapy comprising APS improved quality of life (abstract). Guo teaches that APS is a polysaccharide isolated from astragalus membranaceus, which is a commonly used herbal compound in traditional Chinese medicine, and that the APS was administered by injection, which is interpreted as a liquid (abstract). Guo teaches that after 3 cycles of treatment there were significant differences in the overall patient quality of life (P = 0.003), physical function (P = 0.01), fatigue (P<0.001), nausea and vomiting (P<0.001), pain (P = 0.007), and loss of appetite (P = 0.023) between the two study groups (abstract). One patient who received VC alone achieved a complete response compared with two patients on the VC-APS arm had a complete response, and 35% of patients on the VC arm had a partial response compared with 39% of patients on the VC-APS arm (paragraph bridging pages 1658-1659). Guo further teaches that, overall, 70.6% of patients on the VC-APS arm completed therapy as planned versus 63.2% of patients on the VC arm (page 1659, paragraph 1). Additionally, Guo teaches that a meta-analysis of 34 randomized controlled trials found that astragalus-based Chinese medicines may increase the effectiveness of platinum-based chemotherapy when combined with chemotherapy for patients with NSCLC (page 1660, paragraph 2). Guo discusses another study of patients with stage IIIB/IV NSCLC in which a daily injection of APS along with mitomycin C, vinblastine, and cisplatin (MVP) was compared to treatment with MVP alone and was found to provide a significantly higher response rate, survival rate and improved quality of life (paragraph bridging pages 1660-1661).
Chen discloses a pharmaceutical composition comprising an Astragalus membranaceus extract and pharmaceutically acceptable carrier, excipients or salts [0018]. The extract is comprised of polysaccharides [0040]. Chen teaches that, as a single medicinal material, the Astragalus extract has greater safety and lower side effects in clinical usage than herbal Chinese mixtures containing Astragalus [0015-0016]. Chen discloses a method for obtaining an Astragalus extract comprising mechanically processing Astragalus into chips [0022], putting the chips into an extract solution to extract at a temperature of 80-100 °C for 2-3 hours to obtain a first extract solution [0023], concentrating the first extract solution, then using ethanol or lower alkanol to precipitate and separate [0024]. The method further includes putting the selected precipitates though a centrifugation ultra filter and/or ion exchanger with a high molecular weight cut-off membrane [0025]. Chen provides further details to the method and teaches that, in some embodiments, the precipitation is done by first using a lower concentration of about 35-40% ethanol in a first precipitation step, and then using a higher concentration of about 65-80% ethanol in a second precipitation step. The concentrations of lower alkanol used in the precipitations can range from, among others, 80%-90% [0044]. Chen further indicates that the alkanol washes can be repeated for further purification and that precipitate samples are suspended in water for further processing [0045], which suggests that the precipitate samples are stirred during the alkanol wash steps. Chen further indicates that the crude extract of the alkanol extraction step may be dried using processes such as spray drying, vacuum drying, freeze-drying, critical point drying, solvent exchange, and the like, prior to the ultrafiltration step [0046].
Gonzalez teaches a method of treating cancer comprising administering the monosaccharide mannose, which causes growth retardation in several tumor types in vitro and enhances cell death in response to major forms of chemotherapy (page 719, paragraph 1). Gonzalez teaches that mannose has an anti-tumor effect against A549 cells (extended data figure 1). Mannose represents a well-tolerated means to interfere with glucose metabolism that could potentially be used clinically, either alone or in combination with other forms of cancer therapy (paragraph bridging pages 721-722). Administration of mannose had no negative effect on the health of test subjects (page 721, paragraph 3) and could be a simple, safe and selective therapy in the treatment of cancer (page 719, paragraph 1).
One of ordinary skill in the art would have been motivated to enhance the cancer treatment of Zhou – in which vinorelbine improves the sensitivity of cells to cisplatin and reverses drug resistance – by administering the APS injection of Guo because Guo teaches that APS injections enhance the treatment of vinorelbine + cisplatin. One of ordinary skill in the art would have had a reasonable expectation of success because the teachings of Guo present a method of treating NSCLC and Zhou teaches that the combined therapy of vinorelbine and cisplatin is useful in treating lung cancer.
Furthermore it would have been prima facia obvious before the effective filing date of the claimed invention to add the mannose of Gonzalez to the treatment of Zhou to obtain the predictable result of a method of enhancing the treatment of lung cancer because Gonzalez teaches that mannose has an anti-tumor effect against a variety of cancers including lung cancer A549 cells and teaches that mannose has the potential to be used clinically in combination with other forms of cancer therapy, and Zhou teaches that the combined therapy of vinorelbine and cisplatin is useful for treating lung cancer. Furthermore, it would have been obvious to select astragalus polysaccharides derived by the method of Chen for administration as the astragalus polysaccharides in the treatment of Guo because Guo teaches that the astragalus polysaccharides are isolated from astragalus membranaceus, a commonly used herbal compound in traditional Chinese medicine, and Chen teaches that the Astragalus extract has greater safety and lower side effects in clinical usage than herbal mixtures containing Astragalus.
Claims 8-9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Zhou et al (Asian Pacific Journal of Cancer Prevention, 2013; PTO-892), Guo et al. (Med Oncol, 2012; PTO-892), Chen et al. (US-20150290272-A1, 2015; PTO-892), and Gonzalez et al. (Nature, 2018; PTO-892 01/29/2025), as applied to claim 7, further in view of Sutiman et al. (PLOS ONE, 2016; PTO-892).
The combined teachings of Zhou, Guo, Chen, and Gonzalez suggest the method of instant claim 7, as described in detail above.
The combined teachings of Zhou, Guo, Chen, and Gonzalez differ from that of the instantly claimed invention in that they do not teach a method wherein the chemotherapy drug is a targeted chemotherapy drug.
Sutiman discusses a study evaluation of the tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib in patients with advanced non-small cell lung cancer (NSCLC) (abstract). Sutiman teaches that vinorelbine alone or in combination with cisplatin only modestly improves survival, and more effective treatment approaches are clearly needed for the treatment of advanced NSCLC (page 2, paragraph 2). Sutiman discloses that treatment using the combination of erlotinib and oral vinorelbine is feasible and tolerable in patients with advanced NSCLC who had previously failed standard chemotherapy (page 12, paragraph 1). Sutiman teaches that, considering the safety and tolerability profile of the combination of oral vinorelbine and erlotinib shown in this study, further investigations are warranted to explore the clinical application of this combination (page 14, paragraph 2).
Thus one of ordinary skill in the art would have been motivated to administer a combination of the erlotinib of Sutiman and the combination of the method suggested by the combined teachings of Guo, Chen, Gonzalez, and Zhou in a method of treating drug resistant cancer cells because Sutiman teaches that vinorelbine alone or in combination with cisplatin only modestly improves survival, and more effective treatment approaches are clearly needed for the treatment of advanced NSCLC and suggests combination with erlotinib as a treatment of NSCLC. One of ordinary skill in the art would have had a reasonable expectation of success because the combined teachings of Guo, Chen, Gonzalez, and Zhou present a method of treating NSCLC and Sutiman teaches that treatment using the combination of erlotinib and oral vinorelbine is feasible and tolerable in patients with advanced NSCLC.
Claims 14 is rejected under 35 U.S.C. 103 as being unpatentable over Guo et al. (Med Oncol, 2012; PTO-892) in view of Chen et al. (US-20150290272-A1, 2015; PTO-892) and Gonzalez et al. (Nature, 2018; PTO-892 01/29/2025), as applied to claim 13, further in view of Zhou et al (Asian Pacific Journal of Cancer Prevention, 2013; PTO-892).
The combined teachings of Guo, Chen, and Gonzalez suggest the method of instant claim 13, as described in detail above.
The combined teachings of Guo, Chen, and Gonzalez differ from that of the instantly claimed invention in that they do not expressly teach a method for enhancing the treatment of a chemotherapy drug for a cancer for treating a drug resistant cancer on inhibiting the viability of a cancer cell.
Zhou discusses effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549 cells (abstract) and the effect and mechanism of vinorelbine on reversing the multi-drug resistance (MDR) of lung cancer A549/DDP cells which are drug resistant cells that are resistant to cisplatin (page 4635, paragraph 2). Specifically, Zhou discloses that vinorelbine increased drug sensitivity to cisplatin (abstract). The toxic effect of vinorelbine on A549/DDP increases in a dose dependent manner and is able to enhance the sensitivity of lung cancer A549/DDP cells to cisplatin. (paragraph bridging pages 4636-4637) and vinorelbine inhibited the proliferation of A549/DDP cells (Figure 1). Zhou teaches that this study thus demonstrates that vinorelbine can effectively improve the sensitivity of cells to cisplatin and reverse the drug resistance (page 4638, paragraph 4) and provides experimental basis for the clinical applications in the field of multi-drug resistance reversal of lung tumor cells (page 4639, paragraph 1).
Thus one of ordinary skill in the art would have been motivated to use the method suggested by the combined teachings of Guo, Chen, and Gonzalez in a method of enhancing the treatment of cancer cells that include drug resistant cancer cells because Guo discloses a method of enhancing the combined therapy of vinorelbine and cisplatin and Zhou teaches that the combined therapy of vinorelbine and cisplatin is useful in treating cells that are drug resistant to cisplatin. One of ordinary skill in the art would have had a reasonable expectation of success because the combined teachings of Guo, Chen, and Gonzalez present a method of treating NSCLC and Zhou teaches that the combined therapy of vinorelbine and cisplatin is useful in treating lung cancer.
Response to Arguments
Applicant's arguments filed 08/29/2025 have been fully considered but they are not persuasive.
Insofar as Applicant’s arguments are applicable to the current rejections, Applicant argues that the method of the instant claims denoted by “enhancing chemotherapy drugs” is one of drug sensitization which is primarily intended to enhance the efficacy of chemotherapy for drug-resistant cancers, rather than for general cancer treatment. (Remarks, paragraph bridging pages 6-7). Applicant argues that the teachings of the prior art thus do not render obvious the instant claims. This is not persuasive.
The method of the instant claims are drawn to methods of “enhancing the treatment of a chemotherapy drug.” Under the broadest reasonable interpretation of the claim, enhancing a treatment encompasses any methods that improve the treatment, for example, reducing adverse effects of the chemotherapy treatment, and thus do not require a method of drug sensitization.
Applicant further argues that the data from the currently withdrawn 112(a) rejection of the non-final office action dated 01/29/2025 remains probative in demonstrating that, compared with other conventional Astragalus polysaccharides, the present invention achieves efficacy using a substantially lower concentration of Astragalus polysaccharide (Remarks, page 9, paragraph 7). This is not persuasive.
As stated in the office action dated 06/02/2025, upon further consideration, cell viability studies are known in the art of cancer treatment to be useful for predicting chemotherapeutic treatments in a subject. This instant specification provides cell viability studies for the treatment of ovarian and colorectal cancer cells with a combination of r-APS, mannose, and a chemotherapy drug, and so the instant specification is enabled for the treatment of a subject based on the predictability of the instant claims.
Applicant further argues that the present invention provides unexpected synergistic effects. Applicant states that the proper comparison for assessing synergy involves three groups: (i) the r-APS and mannose combination alone, (ii) the chemotherapy drug alone, and (iii) the r-APS and mannose combination plus chemotherapy drug (Remarks, paragraph bridging pages 11-13). This is not persuasive.
As indicated in the office action of 06/02/2025, the proper groups require testing mannose alone. With the data currently provided, it is not possible to determine what effects are due to the combination of the instant claims and what effects are merely due to the presence of mannose in the treatment. Specifically, Example 1 (beginning on [0048]) compares the treatment of r-APS alone (test group 1), r-APS + mannose (test group 2), and erlotinib alone (test group 3). Example 2 (beginning on [0054]) compares the combined treatment of r-APS and a chemotherapy drug (test group 1) with the combined treatment of r-APS, mannose, and a chemotherapy drug (test group 2). Example 3 (beginning on [0059]) tests the cell viability of HCT116 cells after treatment of r-APS + mannose, and Regorafenib at various concentrations of a r-APS + mannose composition. Finally, Example 4 (beginning on [0072]) tests the cell viability of OVCAR cells after treatment of r-APS + mannose, and Olaparib at various concentrations of a r-APS + mannose composition. MPEP 716.02(e)(II) states that showing unexpected results over one of two equally close prior art references will not rebut prima facie obviousness unless the teachings of the prior art references are sufficiently similar to each other that the testing of one showing unexpected results would provide the same information as to the other. In this case showing unexpected results in the treatment with the combination over the treatment of r-APS alone is insufficient to show that there is also an unexpected result over the treatment of mannose alone, which is necessary because Gonzalez and Guo are both equally close prior art references. Furthermore, none of these examples provide a statistically significant comparison of mannose alone, r-APS alone, a chemotherapy drug alone, and a combination of the r-APS + mannose composition with a chemotherapy drug to allow an analysis of unexpected results. MPEP 716.02(b)(I) states that the evidence relied upon should establish that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. In this case the instant specification has not demonstrated that the differences in results are of statistically meaningful significance. Furthermore, applicant does not have data to support the full scope of the claims, which are drawn to a method of enhancing any chemotherapy treatment including any kind of chemotherapeutic administered to a patient having any kind of cancer cell.
Because Applicant’s arguments are not persuasive, the instant claims are rejected for the reasons of record with modifications made to account for the claim amendments filed 08/29/2025.
Conclusion
No claims are 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 extension fee 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 date of this final action.
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/S.G.H./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693