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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 16, 2016 has been reviewed by the examiner and entered of record in the file.
Application Status
3. Claims 1, 5 and 12 are amended. Claims 8 and 9 are cancelled.
4. Claims 15 and 17-19 (drawn to Group II) remain withdrawn from consideration, as being drawn to a nonelected invention, without traverse, there being no allowable generic or linking claim.
5. The non-elected species were previously withdrawn from consideration, as directed to nonelected subject matter, without traverse.
6. Claims 1, 2, 4-6, 11-13, 21 and 22 are under examination with the elected species and are the subject of this office action.
Previous Claim Rejections - 35 USC § 112(a)
7. 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.
8. Claims 1, 2, 4-6, 11-13, 21 and 22 remain rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for a method of reducing viability of TTFields-resistant glioblastoma multiforme cells in a subject comprising administering the PTGER3 inhibitor L798,106, and those embodied by the instant Specification, is not considered enabled for reducing viability of the full scope of TTFields-resistant cancer cells embraced by “pancreatic cancer, mesothelioma, ovarian cancer, and breast cancer cells, and wherein the cancer cells overexpress EP3” comprising administering any/ all of the other compound species encompassed “PTGER3 inhibitor.” 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.
This rejection has been modified as necessitated by Applicant’s amendment to claim 1.
9. The standard for determining whether the Specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 U.S. 261 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? As recognized by the court in In re Wands, 858 F.2d 731 (Fed. Cir. 1988), that is still the standard to be applied, determined by consideration of the Wands factors (MPEP 2164.01(A)); namely, nature of the invention, breadth of the claims, guidance of the specification, the existence of working examples, state of the art, predictability of the art and the amount of experimentation necessary. All of the Wands factors have been considered, with the most relevant factors discussed below
10. Nature of the Invention: As stated in MPEP 2164.05(a), “[t]he initial inquiry” for determining whether the Specification is enabling “is into the nature of the invention, i.e., the subject matter to which the claimed invention pertains.”
In the instant case, the claimed invention, as amended, is drawn to a method of reducing viability of TTFields-resistant cancer cells in a subject wherein the cells are gliobastoma, pancreatic cancer, mesothelioma, ovarian cancer, or breast cancer cells, wherein the cancer cells overexpress EP3, comprising administering any PTGER3 inhibitor to the subject and administering AEF to the subject.
11. The Relative Skill of those in the Art: Those practitioners who treat cancer(s) of any type (medical clinicians, pharmacists and/or pharmaceutical chemists) presumably would be highly skilled in the art.
12. The State of the Prior Art and the Level of Predictability in the Art: As stated in MPEP 2164.05(a), “[t]he state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains” and, as stated in MPEP 2164.05(b), “[t]he relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed.”
13. As discussed above, the instantly claimed invention is drawn to a method of reducing viability of TTFields-resistant cancer cells in a subject wherein the cells are gliobastoma, pancreatic cancer, mesothelioma, ovarian cancer, or breast cancer cells, wherein the cancer cells overexpress EP3, comprising administering any PTGER3 inhibitor to the subject and administering AEF to the subject.
14. At the time the instant application was filed, it would have been known by those of ordinary skill in the art that “PTGER3 inhibitor” includes any compound that antagonizes the EP3 prostaglandin receptor for prostaglandin E2 (PGE2), which encompasses an extremely broad scope of compounds. The state of the art is that PTGER3 inhibitors have demonstrated anticancer effects against a certain types of cancer cells and may reduce the risk of certain cancers, including ovarian cancer, cervical cancer, breast cancer, gastric cancer, colorectal cancer, liver cancer, bladder cancer, prostate cancer, etc, please refer to the Pubmed.com search, (https://pubmed.ncbi.nlm.nih.gov/?term=ptger3+cancer).
15. Applicants are claiming a method of reducing the viability of TTFields-resistant cancer cells, by administering any PTGER3 inhibitor and applying AEF. The instantly recited method is alleged to treat/prevent TTFields-resistance in various types of cancer/ cancerous cells, in particular glioblastoma, lung cancer, pancreatic cancer, mesothelioma, ovarian cancer, and breast cancer, wherein the cancer cells overexpress EP3. In the instant case, the instant claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to therapeutic effects of the above listed cancers, whether or not the cancer cell line is affected by the inhibition of a certain PTGER3 inhibitor would make a difference. As such, the Specification fails to enable the skilled artisan to use the instant method to reduce viability of the full scope of the recited forms of TTFields-resistant cancers encompassed by claim 1, however the Specification does provide support for reducing viability of certain types of human cancerous cell lines, i.e. human glioblastoma (GBM) as demonstrated in Figures 1, 2, 6, 7a, 11, and 13-19.
16. Even though 3 of the instant PTGER3 inhibitor compounds (specifically aspirin, L798,106 and DG041) may have been identified as having inhibitory activity against PTGER3 as well as anti-cancer activity against GBM cells (Figures 1, 2, 6, 7a, 11, and 13-19), as a practical matter their use as therapeutic agents for reducing viability across the broad range of recited types of TTFields-resistant cancer cells as claimed, remains extremely unpredictable. It is noted that the pharmaceutical art generally is unpredictable, requiring each embodiment to be individually assessed for physiological activity. The court in In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) held that, “in cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved.'' In other words, the more unpredictable an area the more specific enablement is needed in order to satisfy the statute. In the instant case, it has not yet been established in the art that antiproliferative activity would be effective, or even desirable, across the broad range of recited cancer types.
17. Hence, in the absence of a showing of correlation between the full scope of TTFields-resistant cancer cells in a subject, currently encompassed by the language of claim 1, as capable of being treated by any PTGER3 inhibitor, one of skill in the art is unable to fully predict possible results from the recited method for treating the broad scope of TTF-resistant cancers recited in claim 1. There is no question that certain of Applicant’s instant compounds may play a role in future methods of treating some of the aforementioned TTF-resistant cancers (specifically GBM). What is disputed is the claim that the full scope of recited PTGER3 inhibitors could be taken by one skilled in the art at the time of filing and used as treatment for the full scope of cancers/ cancerous cells “wherein the cancer cells overexpress EP3” as embraced by the claims without undue experimentation. There is simply not enough evidence to be found in the literature suggesting that Applicants’ compounds are capable of being used in the manner recited in claim 1, to treat each and every possible TTFields-resistant cancer that is encompassed by the claim language. In essence, there is no absolute predictability in pharmacology, even with compounds whose properties have been determined, despite the extraordinarily high skill possessed by the ordinary artisan.
18. The Amount of Direction Provided by the Inventor / Existence of Working Examples: The amount of direction provided by the Applicant is determined by the Specification and the working examples.
19. In the instant case, the Specification demonstrates the administration of just three PTGER3 inhibitors: aspirin (Figure 13), L798,106 (Figures 14 and 16) and DG041 (Figure 14), against only one TTFields-resistant cancer, i.e., human glioblastoma (GBM) cell lines.
20. The Scope or Breadth of the Claims: As stated in MPEP 2164.01(c), “[w]hen a compound or composition claim is limited by a particular use, enablement of that claim should be evaluated based on that limitation.” Thus, as stated in MPEP 2164.08, “[t]he focus of the examination inquiry is whether everything within the scope of the claim is enabled” (emphasis added). Indeed, the Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’.” In re Wright, 999 F.2d 1557 (Fed. Cir. 1993) (emphasis added).
21. At the same time, however, it is also recognized that not everything necessary to practice the invention need be disclosed. Nor is it necessary that an Applicant test all the embodiments of his invention. In re Angstadt, 537 F.2d 498 (CCPA 1976) (emphasis added). In fact, as stated by the court in In re Buchner, 929 F.2d 660 (Fed. Cir. 1991), a patent need not teach, and preferably omits, what is well known in the art.
22. Accordingly, for purposes of enablement, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate in scope with the protection sought by the claims. Thus, while “a patent application is entitled to claim his invention generically” it is necessary that “he provide a disclosure sufficient to enable one skilled in the art to carry out the invention commensurate with the scope of his claims." Amgen, Inc, v. Chugai Pharmaceutical Co., Ltd. (Fed. Cir. 1991). As noted by the court in In re Fisher, 427 F.2d 833 (CCPA 1970), the scope of enablement must bear a “reasonable correlation” to the scope of the claims. See also Ak Steel Corp. v. Sollac, 344 F.3d 1234 (Fed. Cir. 2003) and In re Moore, 439 F.2d 1232 (CCPA 1971). As stated in MPEP 2164.08, resolution of this concern requires two stages of inquiry: “[t]he first is to determine how broad the claim is with respect to the disclosure. The entire claim must be considered. The second inquiry is to determine if one skilled in the art is enabled to make and use the entire scope of the claim without undue experimentation”.
23. As to the first inquiry, as discussed above, the claims are drawn to a method of reducing viability of TTFields-resistant cancer cells in a subject comprising administering any PTGER3 inhibitor to the subject and administering AEF to the subject. Considering that the claimed “PTGER3 inhibitor” encompasses the entire class of compounds that antagonizes the EP3 receptor for PGE2, including hundreds of compound species, and potentially thousands of compound species, such as any NSAID, any COX2 inhibitor, etc., which includes a broad scope of compounds including flurbiprofen, ketorolac, ketoprofen, tolmetin, aspirin, ibuprofen, naproxen, nabumetone, indomethacin, sulindac, piroxicam, mefenamic acid, meloxicam, diclofenac, celecoxib, etodolac, etoricoxib, lumiracoxib, rofecoxib, diflunisal, oxaprozin, fenoprofen, parecoxib, valdecoxib, and piroxicam, as well as the table of prostanoid EP3 receptor inhibitors disclosed by AAT Bioquest: https://www.aatbio.com/data-sets/prostanoid-ep3-receptor-inhibitors-ic50-ki (which demonstrate drastically different activity in their IC50 values), it is evident that the claims are broad. Further, the generic recitation of “PTGER3” inhibitor reaches through and embraces any future compounds possessing PTGER3 antagonistic ability. Yet, as discussed above, the instant Specification discloses only 3 compound species encompassed by “PTGER3 inhibitor” as recited by the claims.
24. While claim 1 specifies the types of cancer cells that fall within their scope, due to the unpredictable nature of cancer, the various types of recited cancers have different causative agents, involve different cellular mechanisms, and differ in treatment protocol, even if they each overexpress EP3. And, no single compound or class of compounds exist that are known to treat all cancers as a blanket therapeutic, e.g., the Merck® manual currently has many cancer treating agents (over 12,000 compounds), yet they are only known to treat a few cancers each. The argument that the cancer cell(s) recited as treatable by the Applicants are all treated by inhibiting PTGER3 activity because they overexpress EP3 is insufficient support that the claimed method of administering a PTGER3 inhibitor and applying AEF has specific efficacy in current available form for treating all of the TTFields-resistant cancers presently encompassed by claim 1. Applicant has simply not demonstrated that they have sufficient support for the treatment of the recited types of cancer comprising administering any PTGER3 inhibitor.
As such, the claim is extremely broad with respect to the disclosure. The second inquiry is discussed in detail below.
25. Amount of Experimentation Necessary: In view of all of the foregoing, at the time the invention was made, it would have required undue experimentation to practice the entire scope of the invention as claimed. As discussed above, the claims are drawn to administering any PTGER3 inhibitor and applying AEF therapy to reduce viability of any TTFields-resistant cancer cells in a subject. Since identifying any compound which is capable of modulating the activity of a specific receptor, ion channel, or enzyme is extremely complex, the nature of the instant invention considered to be one of extreme complexity. In the instant case, this complexity is exacerbated by the broadness of “PTGER3 inhibitor” and the scope of cancer cells recited with respect to the disclosure since compounds that inhibit PTGER3 encompasses thousands of compound species, whereas the instant Specification discloses only 3 such compound species exerting the disclosed activity on only one type of cancer cell line overexpressing EP3 (glioblastoma). Although the relative skill of those in the art to which the invention pertains is high, the state of the art and unpredictability within the art is such that even the most talented artisan (armed with screening techniques including computer assisted virtual screening techniques such as ligand-based and structure-based design methods) could not reasonably predict which of the hundreds of millions of compounds encompassed by “PTGER3” would exert the alleged activity based on the limited disclosure of 3 active compounds on one cancerous cell line. Although the skilled artisan would have known that certain chemical modifications to the disclosed compounds may predictably provide structurally related compounds having similarly activity, the skilled artisan would have also known that even minor structural changes can, and frequently will, drastically alter or eradicate a parent compound’s ability to modulate the activity of a specific receptor or enzyme. Indeed, as evidenced by AAT Bioquest, PTGER3 receptor antagonists, in particular, demonstrate significant unpredictability since even minor modifications result in drastic changes in activity.
26. After applying the Wands factors and analysis to claims 1, 2, 4-6, 11, 12, 13, 21 and 22, in view of the Applicant’s entire disclosure and the state of the art, it is concluded that the practice of the invention as claimed would not be enabled by the written disclosure. Thus, the specification fails to provide sufficient support for the broad use of any PTGER3 inhibitor for reducing viability of the recited TTFields-resistant cancers that overexpress EP3.
It is suggested to limit the scope of the cancers to be treated to those that are enabled by Applicants' disclosure (glioblastoma), as well as limiting the scope of PTGER3 inhibitors such that they bear a reasonable correlation with the disclosure, i.e., limit the PTGER3 inhibitor to aspirin, L798,106 and/or DG041.
Response to Arguments
27. Applicant traverses the previous enablement rejection, arguing the following points:
(i) Applicant argues that they obviate this ground of rejection by amending claim 1 to recite "wherein the cancer cells overexpress EP3." Applicant argues that the specification establishes sufficient correlation between the disclosed method and the full scope of the recited elements of PTGER3 inhibitor and TTFields-resistant cancer cells that overexpress EP3, because the recited “cancer cells are specifically affected by the very PTGER3-inhibiting action of the "PTGER3 inhibitor". Thus, the cancer cells are specifically affected by the PTGER3 inhibitor by the latter's very nature. It would be well within the ability of a POSITA to establish or confirm that given cancer cells overexpress PTGER3, such that a PTGER3 inhibitor would downregulate overexpression of EP3. Consequently, the present specification discloses enough to reasonably correlate to the entire scope of the claims for both "PTGER3 inhibitor" and the recited TTFields-resistant cancer cells (glioblastoma, pancreatic cancer, mesothelioma, ovarian cancer, and breast cancer cells) wherein the cancer cells overexpress EP3. This suffices to satisfy § 112.” (Applicant’s remarks, page 7).
(ii) Applicant argues that regarding the scope of cancers, claim 1 now recites that the cancer cells overexpress EP3. Applicant contends that the present inventors discovered that EP3 regulates resistance to AEF, in particular via "a regulatory axis anchored by the prostaglandin E2 receptor 3 (EP3) and the transcription factor zinc finger 488 (ZNF488)." Chen et al., Cancer Res (2025) 85 (2): 360-377, Abstract; see also present application at [0058], [0065], [0079], and FIG. 7.” Applicant concludes that based on Chen, “[o]ne would reasonably expect that the Ep3 and znf488 axis exists in other cancers, such that PTGER3 inhibitors in general would be expected to have similar effect in the other cancers recited in the present claims.”
28. Applicant's arguments have been fully considered but they are not persuasive. The examiner respectfully disagrees, since a teaching or suggestion by a prior art reference does not automatically correspond to enablement of the instant claims. The Chen et al. reference (published 2025) teaches that that EP3 overexpression induces TTFields resistance, while EP3 inhibition with aspirin, DG041, or L798106 reverses and/or prevents TTFields resistance in vitro in glioblastoma cells or glioblastoma stem-like cells (Figures 2 and 3 at pages 366-367). Chen et al. demonstrate relative EP3 and ZNF488 levels in other cancer cell lines before and after treatment with TTF (Figure 8, page 374). Chen et al. suggest that inhibiting the EP3- ZNF488 axis mitigates TTFields resistant glioblastoma tumors in mice. Chen et al. go on to teach that while EP3 inhibitors have not been tested in human patients with cancer, the use of aspirin in humans is safe and DG401 has demonstrated safety in mice (page 375, right column, last paragraph). As such, based on the teaching of Chen et al. in 2025, one of skill in the art would reasonably expect that administering an EP3 inhibitor selected from aspirin, DG041, or L798106 would reverse and/or prevent TTFields resistance in glioblastoma cells in a subject in need thereof, with a reasonable expectation of success. As Chen et al. discloses EP3 inhibition using aspirin, DG041, or L798106, and states that EP3 inhibitors have not been tested in human patients with cancer, one of skill in the art would not extrapolate the method of Chen et al. to apply to all PTGER3 inhibitors for reversing TTFields resistance in all types of cancer that overexpresses EP3.
Even if Chen et al. demonstrated that EP3 regulates resistance to AEF in any/all type of cancer that overexpresses EP3 (which it does not), the instant Specification does not support the claim of treating the broad scope of recited cancers that might benefit from the inhibition of EP3, comprising administering any/all PTGER3 inhibitor(s).
(iii) Applicant argues that regarding the scope of PTGER3 inhibitors, the recited scope is sufficiently enabled by the species disclosed in the present application and knowledge in the field as exemplified by Li et al., Oncology Letters, 2018 ("Li"; cited by the Office in asserting obviousness). Applicant alleges that the present application disclosed NSAIDs generally and disclosed specific NSAIDs (a Cox2 inhibitor, L798,106, DG041, aspirin, and ibuprofen); while Li disclosed PTGER3 inhibitors L798106 and Ep3 siRNA (see Li, Figure 2). These two distinct classes of PTGER3 inhibitors (NSAIDs and siRNA) reasonably correlate to the full scope of "PTGER3 inhibitors" to thereby satisfy the enablement requirement. (Applicant’s Remarks, page 8).
Applicant contends that: "As long as the specification discloses at least one method for making and using the claimed invention that bears a reasonable correlation to the entire scope of the claim, then the enablement requirement of 35 U.S.C. 112 is satisfied". M.P.E.P. § 2164.01(b), citing In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). "[T]o comply with 35 U.S.C. 112, first paragraph, it is not necessary to 'enable one of ordinary skill in the art to make and use a perfected, commercially viable embodiment absent a claim limitation to that effect."' M.P.E.P. § 2164.04, citing CFMT, Inc. v. Yieldup Int'l Corp., 349 F.3d 1333, 1338, 68 USPQ2d 1940, 1944 (Fed. Cir. 2003).
(Applicant’s Remarks, page 9).
29. Applicant's arguments have been fully considered but they are not persuasive. Without limitation, the scope of “PTGER3 inhibitor” as presently recited by claim 1 embraces any compound/ agent/ composition etc that antagonizes the EP3 receptor for PGE2, which includes hundreds of compound species, and potentially thousands of compound species: i.e., any NSAID, any COX2 inhibitor, etc., which includes a broad scope of compounds including flurbiprofen, ketorolac, ketoprofen, tolmetin, aspirin, ibuprofen, naproxen, nabumetone, indomethacin, sulindac, piroxicam, mefenamic acid, meloxicam, diclofenac, celecoxib, etodolac, etoricoxib, lumiracoxib, rofecoxib, diflunisal, oxaprozin, fenoprofen, parecoxib, valdecoxib, and piroxicam, as well as the table of prostanoid EP3 receptor inhibitors disclosed by AAT Bioquest: https://www.aatbio.com/data-sets/prostanoid-ep3-receptor-inhibitors-ic50-ki. It is noted that the EP3 inhibitors disclosed by AAT Bioquest demonstrate drastically different activity in their IC50 values, thus it is evident that the claims are broad and the activity of the class of EP3 inhibitors as a whole is unpredictable. Yet, the instant Specification discloses the activity of only three compound species encompassed by “PTGER3 inhibitor” as broadly recited by the claims: L798,106, DG041, aspirin. Li discloses just two PTGER3 inhibitors: L798106 and Ep3 siRNA (see Li, Figure 2). Even though Applicant alleges that the two distinct classes of PTGER3 inhibitors (NSAIDs and siRNA) “reasonably correlate to the full scope of PTGER3 inhibitors,” the instant claims are not drafted commensurate in scope with the alleged unexpected results of the administration of aspirin, L798106 or DG041 on TTFields-resistant glioblastoma cells. That is, the claims are broad and the scope of PTGER3 has substantial variance. Applicant has not sufficiently demonstrated that they have support for successfully treating the full scope of TTFields-resistant cancer cells that overexpress EP3 in a subject, comprising administering any agent that inhibits PTGER3 and applying AEF to said subject.
As such, the previous enablement rejection is maintained.
Previous Double Patenting Rejections
30. 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).
31. 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).
32. 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.
33. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
34. Claims 1, 2, 4-6, and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patent No. 11,911,610 B2.
35. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims recite the following:
Claim 1, as amended, recites a method of reducing viability of TTFields- resistant cancer cells in a subject, comprising: administering a Prostaglandin E Receptor 3 (PTGER3) inhibitor to the subject (more specifically, L798,106 (claims 4 and 21)), and applying an alternating electric field to the cancer cells of the subject, the alternating electric field having a frequency between 100 and 500 kHz (more specifically between 100 and 300 kHz (claim 2)), wherein the cancer cells are selected from the group consisting of glioblastoma, pancreatic cancer, mesothelioma, ovarian cancer, and breast cancer (more specifically, glioblastoma). Claim 5 is drawn to claim 1 and limits the concentration of PTGER3 inhibitor to from about 1 to 500 nanomolar L798,106. Claim 6 is drawn to claim 5, wherein the concentration of the PTGER3 inhibitor in the subject is maintained for at least about 3 days to 5 weeks.
36. The claims of U.S. Pat. No. 11,911,610 B2 are as follows:
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37. Thus, the claims of U.S. Pat. No. 11,911,610 recite the same method of reducing viability of TTFields-resistant glioblastoma cancer cells in a subject, comprising applying an alternating electric field to the subject and administering the PTGER3 inhibitor L798,106 to said subject.
38. As such, one skilled in the art would have been motivated at the time of filing to administer the PTGER3 inhibitor L-798106 with TTFields to enhance the effectiveness of TTFields therapy for reducing cell viability of glioblastoma cells in the treatment of TTFields-resistant glioblastoma cells in a subject in need thereof.
Response to Arguments
39. Applicant traverses the ODP rejection, and argues that upon indication that the ODP rejections are the sole remaining grounds of rejection, terminal disclaimers may be considered if appropriate. Consequently, Applicant requests that the ODP rejection be held in abeyance, pending notice of otherwise allowable subject matter.
40. Accordingly, the nonstatutory double patenting rejection is maintained.
New Claim Rejections - 35 USC § 112(a)
41. 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.
42. Claims 1, 2, 4-6, and 11-13 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.
43. In particular, support cannot be found for the full scope of PTGER3 inhibitors, as instantly recited in the claims.
44. The MPEP §2163 states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. In the case of chemical entities, Applicant's attention is further directed to Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), cert. denied, 523 U.S. 1089, 118 S. Ct. 1548 (1998), which notes that an adequate written description requires a precise definition, such as by structure, formula, chemical name, or physical properties, “not a mere wish or plan for obtaining the claimed chemical invention.” While the court recognizes that, “[i]n claims involving chemical materials, generic formulae usually indicate with specificity what the generic claims encompass” (Id.), it is also recognized that for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim and/or the genus must be sufficiently detailed to show that applicant was in possession of the claimed invention as a whole (see Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555 (Fed. Cir. 1991)). If a genus has substantial variance, the disclosure must present a sufficient number of representative species that encompass the genus in order to adequately describe the genus (i.e., the disclosure must describe a sufficient variety of species to reflect the variation within that genus). See MPEP § 2163. Otherwise, as stated by the court in Ariad Pharmaceuticals, Inc., v. Eli Lilly and Company (Fed. Cir. 2010), “a generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the Applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define the boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result, i.e., “PTGER3 inhibitor.” But the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus.”
45. It is evident that the genus of drugs embraced by the claims has substantial variance, i.e., the scope of “PTGER3 inhibitor” as presently recited by claim 1 encompasses the entire class of compounds that antagonize the EP3 receptor for PGE2, including hundreds of compound species, and potentially thousands of compound species, such as any NSAID, any COX2 inhibitor, etc., which includes a broad scope of compounds including flurbiprofen, ketorolac, ketoprofen, tolmetin, aspirin, ibuprofen, naproxen, nabumetone, indomethacin, sulindac, piroxicam, mefenamic acid, meloxicam, diclofenac, celecoxib, etodolac, etoricoxib, lumiracoxib, rofecoxib, diflunisal, oxaprozin, fenoprofen, parecoxib, valdecoxib, and piroxicam, as well as the table of prostanoid EP3 receptor inhibitors disclosed by AAT Bioquest: https://www.aatbio.com/data-sets/prostanoid-ep3-receptor-inhibitors-ic50-ki (which demonstrate drastically different activity in their IC50 values), it is evident that the claims are broad. Further, the generic recitation of “PTGER3” inhibitor reaches through and embraces any future compounds possessing PTGER3 antagonistic ability. It is noted that the EP3 inhibitors disclosed by AAT Bioquest demonstrate drastically different activity in their IC50 values, thus it is evident that the claims are broad and the activity of the class of EP3 inhibitors as a whole is unpredictable. Thus, the recited genus embraces hundreds of thousands of potential PTGER3 inhibitor compounds that bear no structural resemblance to one another what-so-ever. Yet, the instant Specification discloses the activity of only three compound species encompassed by “PTGER3 inhibitor” as broadly recited by the claims: L798,106, DG041, aspirin.
46. While the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number of species to adequately describe a broad generic. For example, in In re Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d 1008 (Fed. Cir. 1989). In the instant case, it is similarly determined that the disclosure of just three compounds (i.e., L798,106, DG041, aspirin) does not adequately describe a genus embracing hundreds of thousands of possible compounds. That is, the Specification does not disclose a sufficient variety of species to reflect the breadth of the possible compound selections recited in the claims.
47. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate”). Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of compounds and their salts, prodrugs, or derivatives thereof recited in the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
As such, claims 1, 2, 4-6, and 11-13 are rejected.
Claim Objections
48. Applicant is advised that should claims 4 and 21 be found allowable, claims 11 and 22 will be objected to under 37 CFR 1.75 as being substantial duplicates thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Conclusion
49. Claims 1, 2, 4-6, 11-13, 15, 17-19, 21 and 22 are present in the application. Claims 15 and 17-19 are presently withdrawn from consideration. Claims 1, 2, 4-6, 11-13, 21 and 22 are rejected. No claim is presently allowable.
50. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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/JANET L COPPINS/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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