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 .
Status of Claims
Claims 7 and 10-23 are pending.
Priority
Instant application 18/260,602, filed 07/06/2023 claims priority as follows:
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
All references from IDS(s) received 01/11/2024 have been considered unless marked with a strikethrough.
Response to Amendment/Arguments
The amendment filed 12/29/2025 has been entered. Applicant has amended claims 7 and 10-12. Claims 1-6 and 8-9 are cancelled. Claims 17-23 are new. Additionally, the specification has been amended.
In view of the amendments to the specification and claims, applicant has overcome the following objections and rejections previously set forth in the Non-final rejection mailed 10/16/2025:
The objection to the specification;
The objection to claims 11 and 12;
The rejection of claims 9-12 under 35 U.S.C. 112(b);
The rejection of claims 7 and 9-15 under 35 U.S.C. 103 over Munoz in view of Anders;
The rejection of claim 16 under 35 U.S.C. 103 over Munoz in view of Anders, further in view of Van Belle.
Accordingly, the previous objections and rejections are withdrawn.
Claim Objections
Applicant is advised that should claim 11 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate 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).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 7, 10-15, and 17-23 are rejected under 35 U.S.C. 103 as being unpatentable over:
COVENAS (“Neurokinin-1 Receptor Antagonist Aprepitant and Radiotherapy, a Successful Combination Therapy in a Patient with Lung Cancer: A Case Report.” Molecular and Clinical Oncology, vol. 11, no. 1, July 2019, pp. 50–54; cited in IDS) in view of
LINDEMAN (“Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology.” Archives of Pathology & Laboratory Medicine, vol. 142, no. 3, Mar. 2018, pp. 321–46)
COVENAS discloses a combination of the neurokinin‑1 (NK1) receptor antagonist aprepitant and radiotherapy as a successful combination therapy in a patient with non-small cell lung cancer (NSCLC). See the entire document, particularly the abstract, case report, and discussion. COVENAS (page 51, left side) discloses administering 1140 mg/day aprepitant to a patient diagnosed with squamous cell carcinoma having a body weight of 82 kg. 6 months after treatment started, no tumor mass was observed. COVENAS concludes that the patient demonstrated an “excellent response to treatment” (page 53, left side, line 3). COVENAS further teaches that in other pre-clinical studies, it was fully demonstrated that aprepitant, in a concentration-dependent manner, promoted the apoptosis of NSCLC cells (tumor cells die by apoptosis); that these cells overexpress the NK-1R and that the NK-1R is involved in its viability (page 53, left side, 5th para).
With respect to claims 7 and 13-15, while COVENAS discloses administering an NK1 inhibitor (aprepitant) to a patient suffering from NSCLC, COVENAS does not explicitly identify that the cells in the NSCLC tumor have wild type EGFR, ALK, and ROS1 genes.
However, the person of ordinary skill in the art would have reasonably inferred that the patient in COVENAS, having a history of chronic obstructive pulmonary disease (COPD) with NSCLC squamous cell carcinoma, had an extremely high probability of having wild-type EGFR, ALK, and ROS1 genes in the NSCLC tumor cells.
It is a well-established clinical standard that lung squamous cell carcinoma, particularly in patients with a significant smoking history, is almost always negative for the classic driver mutations found in lung adenocarcinomas (i.e. EGFR, ALK, and ROS1). For example, see LINDEMAN, which discloses the guideline recommendations regarding routine testing for oncogenic gene mutations in lung cancer patients. In particular, see page 335, Question 3, which discusses whether molecular testing is appropriate for lung cancers that do not have an adenocarcinoma component. LINDEMAN teaches that the strength of evidence supporting the use of molecular biomarker testing in lung cancers that lack an adenocarcinoma component is insufficient; no new evidence established the routine molecular testing of any genes for typical squamous cell carcinoma, small cell carcinoma, or other neuroendocrine lung tumors; although small studies have reported rare EGFR mutations in squamous cell carcinoma biopsies, these may have represented partial sampling of adenosquamous cancers and have not been borne out in fully resected samples with confirmed squamous histology; evidence from controlled and well-powered studies, supporting the clinical utility of molecular testing of lung cancers for selection of targeted therapies, remains confined to non-squamous non–small cell lung carcinomas, predominantly adenocarcinomas or mixed cancers with an adenocarcinoma component.
The patient in COVENAS had a history of chronic obstructive pulmonary disease (COPD), suggesting a significant smoking history. Further, the researchers focused on NK1 as the molecular target for treatment; rather than administering a tyrosine kinase inhibitor (TKI) which is standard for treating patients having EGFR, ALK, and/or ROS1 mutations.
Finding of prima facie obviousness
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. See MPEP 2143.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying at least KSR example rationale (G), it would have been prima facie obvious to administer an NK1 inhibitor, such as aprepitant, to a patient suffering from NSCLC, wherein at least 1% of the cells have wild type EGFR, ALK, and ROS1 genes in view of COVENAS and LINDEMAN. A person having ordinary would have been motivated to administer aprepitant to this patient population in view of the suggestion from COVENAS and LINDEMAN that it was effective for treating squamous cell carcinoma having wild type EGFR, ALK, and ROS1 genes.
Accordingly, claims 7 and 13-15 are obvious over COVENAS in view of LINDEMAN.
For claims 10-12, 17-19, and 21, COVENAS teaches administering 1140 mg/day aprepitant to a patient having a body weight of 82 kg, which calculates to ~14 mg/kg/day and reads on the recited ranges.
For claims 20 and 22-23, COVENAS teaches a different dosing amount (~14 mg/kg/day) than recited by these claims. However, differences in result-effective variables will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating the value of the result-effective variable is critical. See MPEP 2144.05. In the instant case, the dose of the NK1 inhibitor is considered a result-effective variable that impacts, for example, the occurrence of any side effects, and the dose will be particular to the specific NK1 inhibitor administered. Absent a showing of criticality, optimizing result-effective variables is deemed routine optimization. Accordingly, claims 20 and 22-23 are obvious over COVENAS in view of LINDEMAN.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over:
COVENAS (Molecular and Clinical Oncology, vol. 11, no. 1, July 2019, pp. 50–54; cited in IDS) in view of
LINDEMAN (Archives of Pathology & Laboratory Medicine, vol. 142, no. 3, Mar. 2018, pp. 321–46), and further in view of
VAN BELLE (Expert Opinion on Pharmacotherapy, vol. 9, no. 18, Dec. 2008, pp. 3261–3270; cited previously).
The teachings of COVENAS and LINDEMAN are disclosed above and at least those teachings are incorporated herein by reference and applied to instant claim 16.
As set forth above, COVENAS in view of LINDEMAN teaches administering an NK1 inhibitor to a patient suffering from NSCLC having wild type EGFR, ALK, and ROS1 genes. COVENAS teaches the NK1 inhibitor aprepitant.
COVENAS does not explicitly teach fosaprepitant dimeglumine.
However, fosaprepitant dimeglumine was known in the prior art as an equivalent of aprepitant. For example, VAN BELLE discloses that fosaprepitant dimeglumine is an intravenous neurokinin-1 antagonist (title, abstract). VAN BELLE also discloses that fosaprepitant dimeglumine is the “water-soluble prodrug of aprepitant” and is “converted into aprepitant within 30 min after intravenous administration” (abstract). Further, VAN BELLE teaches that “tolerability of the prodrug is no different from the active drug” (abstract). Finally, VAN BELLE teaches that fosaprepitant dimeglumine has been approved by the FDA as an intravenous substitute for oral aprepitant (abstract).
Applying KSR example rationale (G), it would have been prima facie obvious to administer fosaprepitant dimeglumine to a subject suffering from triple-negative breast cancer in view of the teachings and suggestions of COVENAS in view of LINDEMAN and VAN BELLE. For example, COVENAS in view of LINDEMAN teaches administering aprepitant to patients with NSCLC having wild type EGFR, ALK, and ROS1 genes, and VAN BELLE teaches fosaprepitant dimeglumine as a known prodrug of aprepitant suitable for intravenous administration.
Therefore, claim 16 is obvious over COVENAS in view of LINDEMAN and VAN BELLE.
Conclusion
Claims 7 and 10-23 are rejected.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kyle Nottingham whose telephone number is (571)270-0640. The examiner can normally be reached M-F from 10:00 am - 6:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/K.N./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621