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 .
Priority
The instant application, filed 06/23/2023, is a national stage entry of PPCT/HU2022/050077, filed 11/02/2022, which claims foreign priority to HUP2100375, filed 11/02/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Preliminary Amendments and Claim Status
The amendment filed on 06/23/2023 is acknowledged and entered.
Claims 1-20 are cancelled;
Claims 21-40 are added.
Claims 21-40 are pending and are under prosecution.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/12/2026 is acknowledged and found to be in compliance with the provisions of 37 CFR § 1.97. Accordingly, the information disclosure statement is considered.
Restriction/Election
Applicant’s election with traverse of the following species in the reply filed on 03/11/2026 is acknowledged:
Species A: KRAS mutation: G12C;
Species B: KRAS inhibitor: Sotorasib;
Species C: Farnesyl transferase inhibitor: Lonafarnib;
Species D: Cancer: Lung cancer.
With respect to the traversal of the restriction, the arguments are found not persuasive for the following reasons. Applicant argues that the teachings of the prior art do not disclose or suggest the therapeutic combination claimed in the instant application, and that the combination involves an inventive step. Applicant’s argument is unconvincing because Nagasaka directs a person of ordinary skill in the art towards combination therapies throughout the disclosure, and teaches that both KRAS inhibitors and FTIs are viable for targeted therapy of cancer (pages 1-4 of Nagasaka previously cited). The mere fact that the shared technical feature is known within the art demonstrates a lack of unity, and thus, warrants restriction.
Therefore, the requirement is still deemed proper and is therefore made FINAL.
In accordance with the MPEP § 803.02, if upon examination of the elected species, no prior art is found that would anticipate or render obvious the instant invention based on the elected species, the search of the Markush-type claim will be extended. If prior art is then found that anticipates or renders obvious the non-elected species, the Markush-type claim will be rejected. It should be noted that the prior art search will not be extended unnecessarily to cover all non-elected species. Should Applicant overcome the rejection by amending the claim, the amended claim will be reexamined. The prior art search will be extended to the extent necessary to determine patentability of the Markush-type claim. In the event prior art is found during reexamination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
As per MPEP § 803.02, the Examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species does not make a contribution over the prior art of record.
Status of Claims
Claims 21-36 are pending in the instant application. Claims 23, 29, 30-33, and 35-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention and species. Therefore, claims 21, 22, 24-28, 34, and 40 read on an elected invention and species and are therefore under consideration in the instant application.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code throughout the disclosure (e.g., page 1). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Appropriate correction is required.
Drawings
The drawings filed on 06/23/2023 objected to under 37 CFR § 1.83(a) for the following reason:
The different data types are indistinguishable in Figures 2A, 2C, 3A, and 3C . The original figures rely on color-coding of the data, a feature not available in the black and white drawings. The figures must be remade with larger shapes or line-types used to describe the different data points.
Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). Corrected drawing sheets in compliance with 37 CFR § 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR § 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 U.S.C. § 103
The following is a quotation of pre-AIA 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.
Claims 21, 22, 24-28, 34, and 40 are rejected under 35 U.S.C. § 103 as being unpatentable over Nagasaka et al. (Cancer Treatment Reviews, Volume 101, 102309, published October 21, 2021), hereinafter Nagasaka in view of Baranyi et al (Cancer Metastasis Rev, Volume 39, pages 1127–1141, published June 10, 2020), hereinafter Baranyi.
The instant claims are drawn to a method of treating a patient having a KRAS G12C mutation harboring lung cancer, comprising administering a Farnesyl transferase inhibitor, elected to be lonafarnib, and a KRAS inhibitor elected to be sotorasib.
Nagasaka teaches a method of treating cancer characterized by a KRAS mutation (page 1, Abstract, see instant claim 21), wherein the mutation is KRAS G12C as a primary oncogenic driver in lung cancer (page 2, see instant claims 22, 24, and 28) disease. Nagasaka teaches wherein sotorasib is a KRAS G12C inhibitor approved for the treatment of non-small cell lung cancer (pages 3 and 4, see instant claims 25, 26, and 34). Nagasaka further teaches lonafarnib as a farnesyl transferase inhibitor with evaluated clinical activity in metastatic non-small cell lung cancer (page 3, see instant claims 27 and 34). Nagasaka teaches that KRAS G12C-targeted therapy is effective to treat lung cancer (pages 1-4, see instant claims 28 and 34). The disclosure expressly discusses combination strategies as a way to combat resistance to G12C inhibitors and improve tumor control (page 5, see instant claim 40).
Nagasaka fails to teach that the FTI inhibitor lonafarnib is effective in treating KRAS mutant lung cancer.
The deficiencies of Nagasaka are remedied by Baranyi, who demonstrated that FTIs, specifically lonafarnib, showed statistically significant activity (p=0.007) against KRAS mutant lung adenocarcinoma cell lines as compared to RAS wild-type cells (Table 2, Figures 3-5, see instant claims 27, 28, and 34). Furthermore, Baranyi specifically identifies FTI inhibition as a target for further investigation of KRAS inhibition (page 1137).
Prior to the filing date of the instant claims, it would have been prima facie obvious to a person of ordinary skill in the art to combine these agents as both are taught for the common purpose of treating KRAS mutant lung cancer. According to MPEP 2144.06 (I), combining equivalents known for the same purpose is rendered obvious. The courts have said,
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.).
Beyond the common purpose of treating KRAS mutant lung cancer, a person having ordinary skill in the art would directly be motivated by Nagasaka towards the combination of KRAS inhibitor sotorasib with other agents—because the disclosure highlights that even successful single-agent KRAS inhibition leads to inevitable resistance, especially in the case of KRAS G12C mutants (Abstract). The disclosure by Nagasaki explicitly states that combination strategies with KRAS inhibitors are used as a way to combat G12C inhibitor resistance. Baranyi teaches FTI lonafarnib demonstrates statistically significant activity in targeting mutant KRAS, directly providing a reasonable expectation of success. As such, it would have been obvious to make the combination of sotorasib with lonafarnib in order to more effectively treat lung cancer by combating single-agent resistance to G12C inhibitors. Furthermore, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art (see MPEP § 2143 (I)(A)).
Correspondence
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sophia P. Hirakis whose telephone number is +1 (571) 272-0118. The examiner can normally be reached within the hours of 5:00 am to 5:00pm EST, Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached on +1 (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is +1 (571) 273-8300.
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/SOPHIA P HIRAKIS/Examiner, Art Unit 1623
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
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