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
This application, filed 12/07/2023 is a National Stage entry of PCT/GB2022/051450, International Filing Date: 06/09/2022. PCT/GB2022/051450 claims foreign priority to 2108300.1, filed 06/10/2021; and foreign priority to 2108302.7, filed 06/10/2021. Certified copies of the foreign priority applications are of record.
Status of Claims
Claims 1-2, 4-13, 15, 18, 20, 22, 24, 26, and 28-29 are currently pending, claims 3, 14, 16-17, 19, 21, 23, 25, 27, and 30-32 have been canceled.
Claims 1-2, 4-13, 15, 18, 20, 22, 24, 26, and 28-29 were examined and are rejected.
Claim Rejections-35 USC § 112
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 2, 15, 18, 20, 22, 24, and 26 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 2, 15, 18, 20, 22, 24, and 26 recite a broad recitation, and the claims also recite “preferably…” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
For the sake of compact prosecution, the claims were interpreted with respect to the broader limitations.
Claim 20 refers to NRC-2694 dihydrochloride in parentheses as “NRC-2694-A”, and NRC-2694 monohydrochloride as “NRC-2694-B” in parenthesis. However, Chemical Abstract Services shows “NRC-2694-A” as NRC-2694 monohydrochloride, and “NRC-2694-B” as NRC-2694 dihydrochloride. The claim is therefore confusing, and the metes and bounds aren’t clear. For the sake of providing compact prosecution, the claim was interpreted as if the names within the parentheses weren’t present.
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.
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.
Claim(s) 1-2, 4-13, 15, 18, 20, 22, 24, 26, and 29 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jyothi Prasad et. al., WO 2009090661 A1, publ. 7/23/2009 (cited in an IDS) in view of Abhold et. al., PLOS One, vol. 7(2), e32459, publ. 2012 (cited in an IDS).
Jyothi Prasad teaches 6,7-dialkoxy quinazoline derivatives for treating various types of cancers (title & abstract; p. 1, lines 4-7). Jyothi Prasad teaches the quinazoline compounds having a 3-ethynyl aniline group at the 4th ring position and substituted alkoxy groups at the 6th and 7th positions have significantly enhanced anti-proliferative properties as well as reduced toxicity (p. 2, line 30-p. 3, line 9), and in particular describes NRC-2694:
PNG
media_image1.png
200
400
media_image1.png
Greyscale
. Jyothi Prasad further describes both the mono- and di- HCl salts of NRC-2694 (p. 3, lines 12-15). Jyothi Prasad teaches NRC-2694 as an inhibitor of EGFR having additional advantages, including lower inhibitory concentration, inducing complete tumor regression in an animal model, and showing increased efficacy compared to another EGFR inhibitor, erlotinib (p. 3, line 12-p. 4, line 27; p. 14, lines 2-5). Jyothi Prasad teaches overexpression of EGFR is found in many cancers, including those of the head and neck (p. 2, lines 1-6). Jyothi Prasad teaches an exemplary composition comprising NRC-2694 in an amount of 50 mg. in a tablet dosage form (p. 17, Ex. 8). Administration of NRC 2694 orally and intraperitoneally is exemplified, at doses of 2.5, 5, 10, and 20 mg/kg to animals in a model of lung cancer (p. 16, Table 3). Complete regression of tumors in mice was observed after daily administration of NRC-2694 as well as a significant decrease in tumor invasion (p. 13, line 2-p. 15, line 7).
Jyothi Prasad doesn’t explicitly teach or suggest treating recurrent and/or metastatic squamous cell carcinoma of the head and neck as claimed.
Abhold teaches head and neck squamous cell carcinoma (HNSCC) as a common cancer and despite advances in cancer therapy, survival rates have not improved significantly in more than 30 years (p. 1, 1st para). Abhold teaches EGFR signaling has been implicated in cancer initiation and progression, drug resistance, invasion, and metastasis; additionally, EGFR overexpression is found in up to 80% of HNSCC cases (p. 1, 1st para-p. 2, left col., 1st para). Abhold teaches EGFR activation induces an increase in cancer stem cell (CSC) gene expression, and promotes chemoresistance (p. 3, right col., next to last para; p. 5, 1st para of Discussion). Abhold further teaches combination of the EGFR inhibitor, gefitinib, and cisplatin resulted in sensitization of the HNSCC stem cells to cisplatin, suggesting EGFR inhibition in combination with platinum-based chemotherapy (p. 4, right col., last para-p. 5, left col., top para). Abhold teaches the combination of EGFR inhibition with conventional chemotherapy as a strategy to target both tumor bulk and CSC subpopulation in HNSCC, reducing the potential for relapse and the development of secondary tumors (p. 6, right col., last para-p. 8, last para).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the instantly claimed method of treatment, and have treated a subject in need for treatment of recurrent and/or metastatic HNSCC comprising administering a therapeutically effective amount of the compound NRC-2694, or the mono- or di- HCl salt thereof in consideration of the combined teachings of Jyothi Prasad and Abhold. Jyothi Prasad teaches NRC-2694 to have significantly enhanced anti-tumor properties and reduced toxicity compared to another EGFR inhibitor, erlotinib, and that this compound caused complete tumor regression and suppressed tumor invasion in another tumor model. Although Jyothi Prasad doesn’t explicitly teach treatment of recurrent and/or metastatic HNSCC, Abhold teaches EGFR overexpression is found in up to 80% of HNSCC cases. Moreover, Abhold teaches EGFR activation induces an increase in CSC gene expression, and promotes chemoresistance, and that combination of EGFR inhibition with convention chemotherapy, e.g., cisplatin is a strategy to target both tumor bulk and CSC subpopulation in HNSCC, reducing the potential for relapse and the development of secondary tumors. Therefore, one of ordinary skill in the art would have been motivated to have treated recurrent and/or metastatic HNSCC by administering a therapeutically effective amount of NRC-2694, as this agent is taught to inhibit EGFR, with the reasonable expectation that EGFR activation would have been suppressed, thereby resulting in reduction in tumor size and reduced potential for treatment relapse. Furthermore, one of ordinary skill in the art would have been motivated to have applied this treatment to a subject with HNSCC that is resistant to conventional chemotherapy, e.g., cisplatin, as Abhold suggests EGFR inhibition in combination with cisplatin allowed for sensitization of HNSCC CSCs to cisplatin therapy. As HNSCC is well-known in the art to afflict human adult patients, it would have been prima facie obvious to have administered NRC-2694 to a human adult patient, e.g., between the ages of 18 and 90 years with this condition, as recited by instant claims 15 and 18.
Regarding claim 5, wherein the size of the tumor is reduced from baseline by at least 10%, Jyothi Prasad teaches NRC-2694 therapy resulted in complete regression in a different tumor type. As NRC-2694 inhibits EGFR, and as EGFR inhibition is taught as a strategy to shrink HNSCC tumors, it would have been prima facie obvious to one of ordinary skill in the art to have treated recurrent/metastatic HNSCC by administering NRC-2694, and have had the reasonable expectation that tumor size would have shrunk by at least 10% from baseline.
Regarding claim 6, Abhold teaches EGFR overexpression is found in up to 80% of HNSCC cases, and that this is associated with chemoresistance. Abhold further teaches combining EGFR inhibition with chemotherapy as a strategy to combat chemoresistance. As such, one of ordinary skill in the art would have been motivated to have administered NRC-2694 to a subject with HNSCC that is resistant to chemotherapy, with the reasonable expectation that resistance would have been reduced with NRC-2694 therapy. Similarly, in view of these teachings, one of ordinary skill in the art would have been motivated to have treated HNSCC in a patient that has received at least one line of cancer therapy prior to treatment with NRC-2694 as recited by claim 13, with the reasonable expectation that treatment response would have been enhanced.
Regarding claim 24, although Jyothi Prasad doesn’t explicitly teach so, it is obvious that NRC-2694 was administered in the study models at least once within a day, e.g., once daily. One of ordinary skill in the art would have therefore arrived at this administration frequency of NRC-2694 based on the cited prior art, in the absence of unexpected results.
Regarding claim 26, Jyothi Prasad provides an exemplary composition of a tablet containing 50 mg. NRC-2694, and as discussed above it would have been prima facie obvious to have administered the agent once daily for treatment.
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jyothi Prasad et. al., WO 2009090661 A1, publ. 7/23/2009 in view of Abhold et. al., PLOS One, vol. 7(2), e32459, publ. 2012, and further in view of Pfister et. al., NCCN Clinical Practice Guidelines in Oncology, Head and Neck Cancers, version 2.2020, vol. 18(7), pp. 873-898, publ. July 2020 (cited in an IDS).
The teachings and disclosures of Jyothi Prasad and Abhold as discussed previously are incorporated herein. Jyothi Prasad and Abhold do not explicitly teach or suggest combination therapy of NRC-2694 with paclitaxel and cisplatin as recited by instant claim 28.
Pfister teaches squamous cell carcinoma accounts for more than 90% of head and neck cancers, and primary systemic therapy for this condition includes a combination of cisplatin and paclitaxel (p. 874, 1st para under Overview; pp. 885 & 886, see Other Recommended Regimens in shown images). Additionally, cisplatin and paclitaxel are included as recommended chemotherapeutic agents in metastatic and recurrent disease (p. 886, see Other Recommended Regimens in shown image; p. 888, right col., last para-p. 889, left col., top 2 lines).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the instantly claimed method of treatment and have further incorporated administering cisplatin and paclitaxel with NRC-2694, in consideration of the cited prior art. Jyothi Prasad teaches NRC-2694 to have significantly enhanced anti-tumor properties and reduced toxicity compared to another EGFR inhibitor, erlotinib, while Abhold teaches the combination of EGFR inhibition with conventional chemotherapy, including platinum-based agents as a strategy to target both tumor bulk and CSC subpopulation in HNSCC. Pfister further teaches the combination of cisplatin and paclitaxel within the group of recommended chemotherapy agents for treating both recurrent and metastatic HNSCC. As such, one of ordinary skill in the art would have been motivated to have administered NRC-2694, cisplatin, and paclitaxel to treat a subject in need of treatment for recurrent and/or metastatic HNSCC, with the reasonable expectation that reduction of tumor size would have occurred and tumor invasion would have been inhibited.
Information Disclosure Statements
The IDS filed on 3/7/24, 8/6/24, and 6/16/25 have been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627