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
Status of 18/041,058
Claims 1-11 are currently pending.
Priority
Instant application 18/041,058, filed 2/8/2023, claims priority as follows:
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The provisional application contains support for the instant claims, and thus, claims 1-11 are granted the effective filing date of 8/12/2020.
Information Disclosure Statement
All references from the IDS’s submitted on 9/5/2023 and 10/17/2024 have been considered unless marked with a strikethrough.
Objection to Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 2A, 2B, and 3 are not able to be interpreted as they are in black and white. It is unclear what colors correspond to the labels in the drawings. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Election/Restriction
Applicant’s election of PIK3CA as the gene, recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) as the cancer, and no further administration of a cancer immunotherapeutic in the reply filed 11/12/2025, is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Examination will begin with the elected species. In accordance with 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 examined again. 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 further examination that renders obvious or anticipates the amended Markush-type claim, the claim will be rejected and the action made final.
The elected species was searched and prior art was identified. See the 103 rejection below. The full scope of the claims has not yet been searched in accordance with Markush search practice. Claims 1-6 and 10-11 read on the elected species. Claims 7-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species and/or group, there being no allowable generic or linking claim.
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.
Claim 5 is 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 5 recites, “at least one cancer treatment is a platinum-based chemotherapeutic agent or a PD-1 inhibitor”, and is dependent on claim 1. Claim 1 does not recite “at least one cancer treatment” and thus, a lack of antecedent basis exists. For art purposes, this claim is currently being interpreted as being dependent from instant claim 4, which recites, “at least one cancer treatment prior to the administration of the dose of axitinib”. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Written Description
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-6, and 10-11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, the claims of the instant application embrace a method for treating cancer in a subject comprising:
Determining the presence of a mutation in one or more genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathway in a sample obtained from the subject; and
Administering a dose of axitinib to the subject, whereby the cancer in the subject is treated.
Particularly, the term “one or more genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathway” recited in claim 1 invokes the 35 U.S.C. 112(a) rejection, and claims 2, 4-6, and 10-11 depend from the above claims without resolving the issue. Even a cursory calculation of the number of genes embraced in the instant claims would result in thousands of genes.
Level of skill and knowledge in the art
The level of skill and knowledge in the art is high.
Partial Structure
Examples of the genes involved in the PI3K signaling pathway have been disclosed on pages 8-9, para [0027] of the instant specification:
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However, as to the claimed “one or more genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathway”, no specific examples are given that would demonstrate possession or put the public in possession of all of the genes involved in the PI3K signaling pathway.
Physical and/or chemical properties/functional characteristics
The “one or more genes involved in the phosphoinositide 3-kinase (PI3K) signaling pathway”, are allegedly useful in identifying a patient population for personalized medicine to treat cancer with axitinib. Although the art recognizes generally accepted definitions, the terms are not explicitly defined by the specification in such a way as to demonstrate that the inventor had possession of all of the genes involved in the PI3K signaling pathway.
A review of the prior art identifies the reference Cell Signaling Technology (https://www.cellsignal.com/pathways/pathways-akt-signaling?srsltid=AfmBOooyW9cy6pRe4jVtXKsHf5DXXqc5h3fnWTrtFYu08O9lsvqp2kEJ, revised 3/20/2020, accessed 3/14/2026), that discloses the PI3 Kinase/Akt Signaling pathway:
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The pathway described by Cell Signaling Technology contains additional enzymes, and thus genes, that are involved in the PI3K signaling pathway that are not disclosed by the instant specification. It is unknown which of the genes are involved in the PI3K signaling pathway claimed by Applicant can or will be mutated in a specific cancer, and thus be able to be treated by axitinib. Further, one of ordinary skill in the art would not be able to predict which cancers with mutated genes involved in the PI3K pathway, of the vast number that are claimed, will be able to be treated by axitinib absent evidence.
Method of making the claimed invention
Although the specification provides a method for sequencing each individual patient cancer to identify alterations in TP53, KDR, PIK3CA, PTEN, KMT2C, and KMT2D and treating the individual cancers, no identification of all alterations in all genes involved in the PI3K signaling pathway and subsequent treatment has been disclosed. Methods of treating the myriad of mutated cancers encompassed by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as genes involved in the PI3K signaling pathway are merely described partially.
As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional elements may be present in the genes involved in the PI3K signaling pathway because the examples illustrated in the experimental section are limited to TP53, KDR, PIK3CA, PTEN, KMT2C, and KMT2D.
Substantial and undue experimentation would be needed to practice Applicant’s invention because the specification lacks sufficient detail to show how to use all of the genes involved in the PI3K signaling pathway of the instant invention. Further, there is no guarantee that all of the genes involved in the PI3K signaling pathway embraced by the scope of the claims would be use in treatment of all cancers.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claim(s) are broad and generic with respect to all possible compounds encompassed by the claims: the possible structural variations are limitless to any genes involved in the PI3K signaling pathway. In the instant case, however, the specification does not disclose a sufficient variety of species to reflect this variance in the genus.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims 2, 4-6, and 10-11 do not resolve the 112(a) written description rejections raised in claim 1, since those claims do not further limit or provide further structure of the genes involved in the PI3K signaling pathway. Accordingly, these claims are also rejected.
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 1-6 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Swiecicki (Swiecicki, P. L. et. al. Invest New Drugs, 2015, 33, 1248-1256) and further in view of Millis (Millis, S. Z. JAMA Oncol. 2016, 2(12), 1565-1573). This rejection applies to the elected species.
Determining the scope and contents of the prior art
The reference Swiecicki teaches the administration of axitinib to treat patients with unresectable, recurrent, or metastatic head and neck cancer (abstract and title). Specifically, Swiecicki teaches obtaining a biopsy of the primary lesion or suspected metastatic lesion before treatment (page 1250), which helps teach step (a) of instant claim 1, and further teaches a 76.7% disease control rate metric, which is the sum of patients with a stable disease, a partial response, and a complete response, in patients after administration of a dose of axitinib (page 1250, Table 4).
With respect to claims 4 and 5, the patients of Swiecicki are all heavily pretreated and all have been administered at least one cancer treatment prior to the administration of the dose of axitinib, including a platinum-based chemotherapeutic agent (page 1249, Table 1).
Regarding claim 6, as stated above, the sample taken from patients of Swiecicki in a biopsy is tumor tissue or suspected tumor tissue (page 1250).
With respect to claim 10, the patients of Swiecicki were administered a dose of 5mg by mouth twice daily (page 1249).
The reference Millis teaches that molecular aberrations in the PI3K pathway drive tumorigenesis, and sequenced a large number of solid tumors to identify mutations in an effort to discover novel targeted therapy opportunities in clinical practice (abstract). Specifically, Millis teaches obtaining tissue samples from solid tumor patients that were then sequenced (page 1566), which helps teach step (a) of claim 1, and found that 14% of head and neck squamous cell carcinomas contain a PIK3CA mutation (page 1568).
Ascertaining the differences between the prior art and the claims at issue
The reference Swiecicki fails to teach an anticipatory species of a determining the presence of a mutation in one or more genes involve in the PI3K signaling pathway, whereas the reference Millis fails to teach a method of treating cancer in a subject by the administration of axitinib.
Resolving the level of ordinary skill in the pertinent art
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of methods of treating cancer with a mutation in one or more genes involved in the PI3K pathway with axitinib. An artisan possess the technical knowledge necessary to make adjustments to the methods of treatment to enhance their effectiveness. Said artisan has also reviewed the problems in the art as regards to use of said methods of treating cancer with a mutation in one or more genes involved in the PI3K pathway with axitinib and understands the solutions that are widely known in the art.
Considering objective evidence present in the application indicating obviousness or nonobviousness
Applying KSR prong (A), it would have been prima facie obvious for one of ordinary skill in the art to combine the teachings of Swiecicki and Millis to arrive at the instant method of treating cancer because axitinib, as taught by Swiecicki, is already known to treat HNSCC, and Millis, identifies a specific patient population with a PIK3CA mutation in HNSCC. A skilled artisan would immediately recognize approximately 14% of the patient population of Swiecicki contains a PIK3CA mutation as per the teachings of Millis, and would immediately be motivated to combine the two references to improve treatment of head and neck squamous cell carcinoma. One of ordinary skill would have readily predicted success, or improvement, of the instant method claims in light of the teachings of Swiecicki and Millis.
Conclusion
Claims 1-6 and 10-11 are rejected. Claims 7-9 are withdrawn.
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/K.N.H./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621