DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Status 03/23/2026 has been entered.
3. Claims 22, 25 and 46-50 are pending.
4. Claim 50 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
5. Claims 22, 25, and 46-49 are under examination as they read on a composition comprising an agent that inhibits EGFR signaling and isoniazid, and the species of erlotinib as the agent that inhibits EGFR signaling.
5. Applicant’s IDS, filed 05/21/2026, is acknowledged.
6. 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.
7. Claims 22, 25 and 45-49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 18, 28, 32-34 of copending Application No. 17910637 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `637 application are directed to the use of (A) EGFR inhibitors which is a tyrosine kinase inhibitor such as erlotinib and (B) an agent that modulates Nrf2 singling such as isoniazid. The `637 application further claims a pharmaceutical composition comprising the erlotinib and isoniazid. The claims of the `637 application anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Applicant’s arguments, filed 03/23/2026, have been fully considered, but have not been found convincing.
Applicant requests that the NS-ODP rejection be held in abeyance until such time as the Examiner otherwise finds allowable subject matter.
The rejection is maintained for the reasons of record.
7. Dr. Habib declaration, filed 03/23/2026, under 37 CFR §1.132 is sufficient to overcome the following 103 rejections below for the flowing reasons.
A. All the rejections under 35 U.S.C. 103 as being unpatentable over Yamadori et al (Journal of Clinical Oncology, Vol 38(15), May 2010, ASCO Annual Meeting) in view of Verma et al (Redox Biology 6 (2015) 80–92, IDS) or Zhu et al (Free Radical Biology and Medicine, 99:544-556, 2016, of record).
B. All the rejections under 35 U.S.C. 103 as being unpatentable over Kankia et al (Oxidative Medicine and Medicine and Cellular Longevity, 2017, Article ID 1864578, 19 pages) in view of Verma et al (Redox Biology 6 (2015) 80–92, IDS) or Zhu et al (Free Radical Biology and Medicine, 99:544-556, 2016, of record).
C. All the rejections under 35 U.S.C. 103 as being unpatentable over Zhang et al (Bioscience Hyotheses, 2, 261, 2009, IDS) in view of Verma et al (Redox Biology 6 (2015) 80–92, IDS) or Zhu et al (Free Radical Biology and Medicine, 99:544-556, 2016, of record) and US 20040147418.
The declaration at ¶11 states that it is Dr. Habib’s opinion that the claimed combination f an EGFR inhibitor (e.g., erlotinib, afatinib) and isoniazid is significantly more effective at treating glioblastoma than alterative treatment regimens. These superior results were unexpected. The declaration at ¶16 states that the combination of an EGFR inhibitor and isoniazid should be even more therapeutically effective than would have been expected if isoniazid was solely operating as a Nrf2 inhibitor, as surmised by the cited references In other works, but for the understanding that isoniazid is a TNF inhibitor, one of skill in the art would not have expected that combining isoniazid with an EGFR inhibitor would be as effective as it was.
The declaration at ¶21 states that these data demonstrate that the combination of isoniazid and an EGFR inhibitor such as erlotinib or afatinib results in a synergistic effect. Further, the synergism
observed with the claimed combination was completely unexpected. As detailed above, the
skilled artisan did not appreciate the role that EGFR inhibition plays on TNF and further did not
appreciate that isoniazid is a TNF inhibitor. As such, the skilled artisan would not have
expected the improvements to be as notable as they are here. Moreover, as detailed above,
evern knowing these relationships, as I did, the observed improvements were still remarkable.
Survival rate more than double.
The declaration at ¶22 states that as an expert in the fields of neurology and neurotherapeutics, I conclude that the data detailed herein indicate that administering an EGFR inhibitor (e.g., erlotinib, afatinib) in combination with isoniazid is superior for treating glioblastoma and that such superiority is unexpected. Therefore, it is my opinion that the claimed invention is patentable over the cited references.
Upon updating the search, the Examiner uncover prior art references that apply to the amended claims.
8. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
9. Claims 22 and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al (A) (J Thorac Dis 2017;9(8):E709-E713).
Lee et al teach a regimen of anti-TB medications, Isoniazid 300 mg/Pyrazinamide 1,500 mg/Moxifloxacin 400 mg were selected due to possible drug-reaction between rifampin and erlotinib and initial decreased visual acuity of patient due to the choroidal metastasis (ethambutol was skipped) (page E711, right col., top ¶). The referenced treatment regimen must be in pharmaceutically acceptable carrier since it was used for in vivo treatment.
The term “comprising” in base claim 1 is open-ended, it would open up the claims to included the additional material recited in the reference.
Evidence of secondary considerations, such as unexpected results or commercial success, is irrelevant to 35 U.S.C. 102 rejections and thus cannot overcome a rejection so based. In re Wiggins, 488 F.2d 538, 543, 179 USPQ 421, 425 (CCPA 1973). As such, Applicant’s Declaration regarding that the superior unexpected results/synergistic results have not been found persuasive.
The reference teachings anticipate the claimed invention.
10. Claims 22 and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al (B) (American Journal of Respiratory and Critical Care Medicine, (2017) Vol. 195. Abstract Number: A6013).
Lea et al reported the use of anti-tuberculosis medication without change of chemotherapy regimen, composed of isoniazid, pyrazinamide and moxifloxacin except rifampin due to the possible drug interaction with erlotinib (oral TKI) in the treatment of pulmonary tuberculosis in a patient diagnosed non-small cell lung cancer. The referenced treatment regimen must be in pharmaceutically acceptable carrier since it was used for in vivo treatment.
The term “comprising” in base claim 1 is open-ended, it would open up the claims to included the additional material recited in the reference.
Evidence of secondary considerations, such as unexpected results or commercial success, is irrelevant to 35 U.S.C. 102 rejections and thus cannot overcome a rejection so based. In re Wiggins, 488 F.2d 538, 543, 179 USPQ 421, 425 (CCPA 1973). As such, Applicant’s Declaration regarding that the superior unexpected results/synergistic results have not been found persuasive.
The reference teachings anticipate the claimed invention.
11. 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.
12. Claims 22, 25, and 46-49 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (A) (J Thorac Dis 2017;9(8):E709-E713) or Lee et al (B) (American Journal of Respiratory and Critical Care Medicine, (2017) Vol. 195. Abstract Number: A6013) each in view of US 20200197397 (of record).
The teachings of Lee et al (A) and Lee et al (B) have been discussed, supra.
The reference teachings differ from the claimed invention only in the recitation that the composition is formulated as a single dosage form in claim 46, as an oral solid dosage from in claim 47, as an injectable dose form in claim 49, wherein the oral solid dosage form is a tablet or a capsule in claim 48.
The `397 publication teaches that the EGFR inhibitor erlotinib is sold as oral tablets (Tarceva). Similarly, gefitinib (Iressa), osimertinib (Tigresso) and brigatinib (Alunbrig) are sold as oral tablets [0004]. In addition, there are advantages in topically treating skin disorders by topical or injectable instead of systemic administration, thus avoiding systemic side-effects, provided the cutaneous EGFR inhibitors side-effects can be avoided, prevented or minimized [0039], [0080]-[0086] [0136], [0139], published claims 74-75, 77, 79.
It would have been obvious to one of ordinary skill in the art before the effective filing date of Applicants' invention was made to formulate the treatment regimen taught by Lee et al references teachings as single dose, oral solid dose, tablet or capsule and injectable dosages formulation as taught by the `397 publication to ensure the EGFR inhibitors are safe, effective, stable and delivered to the correct site in the body because formulating is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Further, the determination of the optimal dosage formulation of treatment is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. It has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II.
A person having ordinary skill in the art would have found it obvious to determine the optimum composition formulation that treat of pulmonary tuberculosis in a patient diagnosed non-small cell lung cancer of result-effective variables known in the art. Recognition that a property (treating pulmonary tuberculosis in a patient diagnosed non-small cell lung cancer) is affected by the variable (formulating a composition) is sufficient to find the variable result-effective. The experimentation needed to arrive at the subject matter claimed was "nothing more than routine" application of a well-known problem-solving strategy, we must conclude it is not invention. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed. Cir. 2007).
"[I]t is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955); see also In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003). "Only if the 'results of optimizing a variable' are 'unexpectedly good' can a patent be obtained for the claimed critical range." In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997) (quoting In re Antonie, 559 F.2d 618, 620 (CCPA 1977)). "[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
It is clear that both the prior art and claimed method administer the same treatment to achieve the same results. It would be conventional and within the skill of the art to determine the specific composition formulation of erlotinib and isoniazid in the treatment of pulmonary tuberculosis in a patient diagnosed non-small cell lung cancer. Further, it has been held that where the general conditions of a claim are disclosed in the prior art , discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 220 F2d 454,456,105 USPQ 233; 235 (CCPA 1955). see MPEP § 2144.05 part II A.
The determination of the optimal intervals of treatment is well within the purview of one of ordinary skill in the art at the time the invention was made and lends no patentable import to the claimed invention. The duration of treatment, the specific rout of administration, composition formulation and like factors within the knowledge and expertise of the medical practitioner.
From the combined 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.
13. No claim is allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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July 27, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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