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 .
DETAILED ACTION
This action is in response to Applicant’s amendment filed August 11, 2026 in reply to the First Office Action on the Merits mailed February 11, 2026. Claims 1, 11, 14, and 15 have been amended; claims 2, 3, 5, 6, and 13 have been canceled; and claims 16 and 17 have been newly added. Claims 4, 10 and 12 have been withdrawn. Claims 1, 7-9, 11, and 14-17 are under examination.
***It is noted that Applicant’s elected species of composition constituent is “perillyl alcohol”, not “perillyl alcohol carbamate covalently bound to a chemotherapeutic agent”. Hence, claims 4 and 12 have been withdrawn. Furthermore, Applicant’s elected species of additional therapeutic agent is “chemotherapeutic agent”, and Applicant’s elected species of chemotherapeutic agent is “dimethyl celecoxib”. Claim 11 has been amended to stipulate that the method “further comprises” administering to the subject a composition that comprises e.g. perillyl alcohol with another chemotherapeutic agent, which is indefinite for reasons detailed below.
Abstract
The abstract of the disclosure remains objected to because of the following:
1. The abstract should be a concise summary of the key technical aspects of the invention which are new to the art to which the invention pertains. If the invention pertains to a composition, the abstract should recite the key requisite ingredients. If the invention pertains to a method, the abstract should recite the key requisite active steps.
2. In this case, the abstract merely informs the reader that the invention is an intranasal glioblastoma therapy with perillyl alcohol. This is not new to the art at all.
3. The abstract should not refer to purported merits or speculative applications of the invention, and also should not compare the invention with the prior art (e.g. “improved”). However, this is precisely what the abstract continues to do. The abstract should adequately inform the reader what the product or method actually is in technical terms, requisite constituents or requisite active steps, not serve as a promotional advertisement for the product or method.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claim 11 is objected to because of the following:
i) In claim 11, there is an extraneous “the” in the phrase “to the the subject in need thereof”; and an extraneous comma between “in need thereof” and “the pharmaceutical composition”.
Appropriate correction is required.
Obviousness-Type Double Patenting (I and II)
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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.
I. Claims 1, 7-9, 11, and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-17 of U.S. Patent No. 9,499,461, in view of Parsons et al. (Science. 2008; 321: 1807-1812).
Applicant’s elected subject matter is directed to a method of treating glioblastoma in a patient that has a mutated isocitrate dehydrogenase 1 (IDH1) gene comprising administering intranasally to the patient via a nebulizer a composition comprising perillyl alcohol and dimethyl celecoxib.
Claims 10-17 of U.S. Patent No. 9,499,461 disclose a method of treating e.g. glioblastoma in a patient comprising administering e.g. intranasally to the patient a composition comprising e.g. perillyl alcohol and dimethyl celecoxib. U.S. Patent No. 9,499,461 discloses that by intranasal administration is meant e.g. with a nebulizer.
Parsons et al. disclose that a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma.
Although claims 10-17 of U.S. Patent No. 9,499,461 do not explicitly disclose that the patient being treated has a mutated isocitrate dehydrogenase 1 (IDH1) gene, since Parsons et al. disclose that a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma; one of ordinary skill in the art would thus be motivated to apply the method of claims 10-17 of U.S. Patent No. 9,499,461 specifically to those patients diagnosed with glioblastoma that have a mutated isocitrate dehydrogenase 1 (IDH1) gene, with the reasonable expectation that the method will successfully treat the cancer.
II. Claima 1, 7-9, 11, and 14-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 9,700,524 in view of Parsons et al. (Science. 2008; 321: 1807-1812).
Applicant’s elected subject matter is directed to a method of treating glioblastoma in a patient that has a mutated isocitrate dehydrogenase 1 (IDH1) gene comprising administering intranasally to the patient via a nebulizer a composition comprising perillyl alcohol and dimethyl celecoxib.
Claims 1-9 of U.S. Patent No. 9,700,524 disclose a method of treating e.g. glioblastoma in a patient comprising administering e.g. intranasally to the patient a composition comprising e.g. perillyl alcohol and dimethyl celecoxib. U.S. Patent No. 9,700,524 discloses that by intranasal administration is meant e.g. with a nebulizer.
Parsons et al. disclose that a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma.
Although claims 1-9 of U.S. Patent No. 9,700,524 do not explicitly disclose that the patient being treated has a mutated isocitrate dehydrogenase 1 (IDH1) gene, since Parsons et al. disclose that a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma; one of ordinary skill in the art would thus be motivated to apply the method of claims 1-9 of U.S. Patent No. 9,700,524 specifically to those patients diagnosed with glioblastoma that have a mutated isocitrate dehydrogenase 1 (IDH1) gene, with the reasonable expectation that the method will successfully treat the cancer.
Claim Rejections - 35 USC § 112(b)
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 11 and 14-17 are 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.
Claim 11, which depends from claim 1, stipulates that the method “further comprises” administering a composition “comprising perillyl alcohol or perillyl alcohol carbamate in combination with another chemotherapeutic agent”, which renders the claim indefinite for the following reasons:
1. First, claim 1 already requires administering a composition that “comprises perillyl alcohol or perillyl alcohol carbamate covalently bound via a carbamate linking group to a chemotherapeutic agent”. One of ordinary skill in the art thus cannot definitively ascertain what, in fact, is necessarily being administered in claim 11. For example, is one composition being administered that now further contains a free chemotherapeutic agent (i.e. that is not covalently bound to the perillyl alcohol carbamate), or are there now two compositions being administered, i.e. the one from claim 1 and now another one that further includes a free chemotherapeutic agent?
2. Or, alternatively, is claim 11 administering a composition that comprises either perillyl alcohol, or perillyl alcohol carbamate covalently bound via a carbamate linking group to a different chemotherapeutic agent, or are there now two compositions being administered, one comprising either perillyl alcohol, or perillyl alcohol carbamate covalently bound via a carbamate linking group to the chemotherapeutic agent of claim 1, and another comprising either perillyl alcohol, or perillyl alcohol carbamate covalently bound via a carbamate linking group to a different chemotherapeutic agent. Or what?
3. One of ordinary skill in the art cannot definitively ascertain from the phrase “another chemotherapeutic agent” whether the chemotherapeutic agent of claim 11 must necessarily be the same chemotherapeutic agent from claim 1, or rather must necessarily be a different chemotherapeutic agent from claim 1. For example, does the claim mean that if the chemotherapeutic agent of claim 1 is e.g. dimethyl celecoxib, the chemotherapeutic agent of clam 11 must necessarily be another dimethyl celecoxib, or must necessarily be another chemotherapeutic agent that is not dimethyl celecoxib, such as e.g. temozolomide? Or what” Hence, one of ordinary skill in the art cannot definitively ascertain the metes and bounds of the claimed subject matter.
***For examination at this time, since the elected species of composition constituent is “perillyl alcohol”, and the elected species of chemotherapeutic agent is “dimethyl celecoxib”, the claim is being interpreted as one composition is being administered that comprises perillyl alcohol and dimethyl celecoxib.
Claims 14 and 15, which depend (ultimately) from claim 1, stipulate in a wherein clause that the composition comprises perillyl alcohol which has a “purity” as recited, e.g. greater than about 99% (w/w). The claims, however, are directed to a method of treating recurrent glioblastoma in a subject, and the claims require the administration of a composition that comprises perillyl alcohol. Hence, even if one constituent is “pure” perillyl alcohol, in view of the “comprising” transitional phrase, the composition could include just about anything else in one amount or another, i.e. nothing is necessarily excluded. In this context, the limitations of claims 14 and 15 appear to be effectively meaningless. One of ordinary skill in the art thus cannot definitively ascertain what element(s) are necessarily further included in or excluded from the composition being administered by the “purity” limitations recited.
***For examination at this time, claims 14 and 15 are being interpreted essentially as a product-by-process limitation, i.e. the perillyl alcohol employed as a constituent element has the recited purity, but once in the composition as a whole this purity value has no real meaning as the composition could further include any additional, unrecited element in any amount.
Claims 16 and 17, each of which depends from claim 11, stipulate in a wherein clause that “the chemotherapeutic agent” is selected from those recited. Claim 11, which depends from claim 1, has introduced two chemotherapeutic agents, one that is covalently linked to a perillyl alcohol carbamate, and “another” chemotherapeutic agent. One of ordinary skill in the art cannot definitively ascertain whether “the chemotherapeutic agent” is necessarily the one covalently bound to the perillyl alcohol carbamate, the “another” chemotherapeutic agent, either one, or both of them.
Claims 15 and 16 are (also) indefinite for depending from an indefinite claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 7-9, 11, and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (U.S. Patent Application Pub. No. 2016/0158162), in view of Parsons et al. (Science. 2008; 321: 1807-1812).
Applicant Claims
Applicant’s elected subject matter is directed to a method of treating recurrent glioblastoma in a subject that has a mutated isocitrate dehydrogenase 1 (IDH1) gene comprising administering intranasally to the patient via a nebulizer a composition comprising perillyl alcohol and dimethyl celecoxib.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
Chen et al. disclose a method of treating e.g. recurrent glioblastoma in a patient comprising administering e.g. intranasally to the patient via a nebulizer a composition comprising e.g. perillyl alcohol and dimethyl celecoxib (see e.g. abstract; paragraphs 0005, 0007, 0012, 0013, 0015, 0073, 0074, 0084, 0112, 0126, 0152; 0167; claims 8, 10, 14, 15, 20).
Parsons et al. disclose that a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma.
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Chen et al. do not explicitly disclose that the patients with glioblastoma being treated have a mutated isocitrate dehydrogenase 1 (IDH1) gene. This deficiency is cured by the teachings of Parsons et al.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Chen et al. and Parsons et al., outlined supra, to devise Applicant’s presently claimed method.
Chen et al. disclose a method of treating cancer in a patient comprising administering e.g. intranasally to the patient via a nebulizer a composition comprising e.g. perillyl alcohol and dimethyl celecoxib; wherein the cancer can be glioblastoma. Since Parsons et al. disclose that a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma; one of ordinary skill in the art would thus be motivated to apply Chen et al.’s glioblastoma treatment specifically to those patients diagnosed with glioblastoma that have a mutated isocitrate dehydrogenase 1 (IDH1) gene, with the reasonable expectation that the method, applied specifically to these patients diagnosed with glioblastoma and that have a specific marker for glioblastoma, will successfully treat the cancer.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed August 11, 2026 have been fully considered but they are not persuasive.
i) Applicant contends that “the present invention is directed to recurrent glioblastoma”; that “Chen does not teach administering compositions of perillyl alcohol…to individuals in a specific subset of patients with recurrent glioblastoma and a mutated isocitrate dehydrogenase 1 (IDH1) gene”; that “Parsons teaches that IDH1 is a specific marker for secondary glioblastoma wherein…cancers that have clinical, radiologic, or histopathologic evidence of malignant progression from a pre-existing lower-grade tumor, not recurrence”; that “the IDH1 gene mutation is a known predictor of better overall survival in malignant glioblastoma”; that “the present invention teaches that prolonged survival of recurrent glioblastoma patients with the IDH1 mutation is achievable through administration of the perillyl alcohol composition”, and that “it would not have been obvious to one of ordinary skill in the art that administering…perillyl alcohol…to patients (subjects) with recurrent glioblastoma having the IDH1 mutation would result in prolonged survival rates”.
The Examiner, however, would like to point out the following:
1. As anyone of ordinary skill in the art would know, “recurrent glioblastoma” is a glioblastoma that returns or “grows back” following a previous treatment, such as surgery, radiation, or chemotherapy. Recurrent glioblastoma is typically treated by repeat surgery, re-irradiation, or an alternative chemotherapeutic drug.
2. Chen teaches the treatment of glioblastoma generally, including treatment of recurrent glioblastoma, with perillyl alcohol. In particular, Chen teaches treatment of recurrent gliomas with perillyl alcohol, and treatment of glioblastoma that has shown to be resistant to treatment with temozolomide. It would be prima facie obvious for one of ordinary skill in the art to thus treat recurrent glioblastoma with perillyl alcohol and a chemotherapeutic agent, such as dimethyl celecoxib.
3. Applicant has not clearly articulated why treatment of recurrent glioblastoma with perrilyl alcohol is somehow now rendered a patentable advance if the subject has a mutation in the IDH1 gene. As Parsons discloses, a mutated isocitrate dehydrogenase 1 (IDH1) gene is a marker for human glioblastoma occurring specifically in a large fraction of young patients and in most patients with secondary glioblastoma. This was known at the time of filing the present application. If anything, if the mutation in the IDH1 gene is found more often in secondary glioblastomas and predicts a slower disease progression and longer overall survival, it would seem that this form of recurrent glioblastoma would be expected to be more amenable to treatment with perillyl alcohol and dimethyl celecoxib than the more malignant and aggressive forms of the cancer with significantly shorter survival times.
For the foregoing reasons, the 35 USC 103 rejection is hereby maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DAVID BROWE/Primary Examiner, Art Unit 1617
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