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 .
Election/Restrictions
Applicant’s election without traverse of Group I and TP53 without traverse in the reply filed on 6/11/2026 is acknowledged.
Improper Markush Grouping
Claims 19-22, 32-36, and 46-47 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the listing of different nucleic acids encoding different polypeptides is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The different methods for detecting mutants do not share a common structure because the genes themselves do not share a common structure. There is no expectation from the prior art that these would all work interchangeably in the claimed method, and the specification also demonstrates different mutation profiles with regard to which genes are present in OSCC or indolent OLP or in OLP that is not indolent (see example 1).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 19-22 and 32-33 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon without significantly more. The claim(s) recite(s) “determining that a cell of said OLP comprisies a mutant version” with no step recited to limit the “determining.” Thus, the claim encompasses reviewing data, such as a medical chart, to accomplish the determining and this is a mental process abstract idea. The claims further recite “thereby identifying said OLP as being likely to progress to OSCC” which sets forth a natural phenomenon: the relationship between gene mutation(s) and OSCC. This judicial exception is not integrated into a practical application because the step of administering an “immunosuppressive or immunomodulatory agent” is extremely broad, and not all agents within this class are reasonably considered to be treatments for OLP, and in particular OLP that is indicated to progress to OSCC. There is no nexus between the treatment and the judicial exception. Claim 33 recites the broad class of immunosuppressive or immunomodulatory agent that is a biologic agent” which still is not specific and encompasses biologic agents that are not OLP treatments. Furthermore, since the other recited treatments are treatments that would be routinely used to treat all OLP, regardless of genotype, there is no nexus between these treatments and the natural phenomenon JE. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the only step in addition to the judicial exception is to treat the patient using routine treatments see Najafi and Lavanya, of record.
Claim(s) 19, 20, 32, 33, 34, 35, 46, and 47 is/are rejected under 35 U.S.C. 103 as being unpatentable over Najafi (US 2014/0249118) in view of Tabatabaei (IDS 1/22/26) and Safuanovna (RU250222C1).
Citations in this Office action to Safuanovna are to the machine translation, which is attached to the publication.
Najafi teaches a method of treating patients with oral lichen planus (OLP) by administering a combination of triamcinolone and retinoic acid, wherein triamcinolone is a corticosteroid (title and abstract). Najafi teaches that long-standing oral lichen planus may develop into squamous cell carcinoma of the mouth (¶ 17). The patients are men and women, wherein men and women are humans (¶ 30). While Najafi teaches a method of treating a mammal having OLP, the reference does not teach a determining that a cell of said OLP comprises a mutant version of nucleic acid encoding a TP53 polypeptide.
Tabatabaei teaches determining the presence of a Proline mutation at codon 72 in patients having oral lichen planus. The reference teaches in OLP the mutation was higher that than in the control patients, with the proline allele in OLP being more frequent than arginine allele (p. 248, 2nd column). The reference teaches that the results of the study might indicate premalignant potential of OLP and that the proline polymorphism might be a genetic predisposing factor for conversion to carcinoma. Tabatabaei teaches directly detecting the mutation in nucleic acid encoding a TP53 polypeptide (p. 247, Col. 1-2).
Further, Safuanovna et al. teaches that the Proline allele of this same mutation is indicative of a malignant transformation of the erosive-ulcerative form of oral lichen planus. See ¶0001 and throughout. The reference teaches that identifying genotypes with an increased risk of developing malignant neoplasms of the oral mucosa at the preclinical stage of the disease would allow for the implement of therapeutic measures in carriers of the risk genotypes (¶0078).
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to combine the method of treating oral lichen planus of Najafi, with the method of detecting tp53 mutation in a patient having oral lichen planus, to arrive at the instantly claimed methods. One of ordinary skill in the art would have been motivated to combine the methods of Najafi with the methods of Tabatabaei because both Tabatabaei and Safaunovna teach detection of mutation in p53 in patients with OLP, and suggest monitoring and treating such patients. Furthermore, it is prima facie obvious to combine known elements in the art, a method of detecting p53 mutation in OLP and a method of treating lichen planus, to yield the predictable result of assaying and treating lichen planus. Regarding the thereby clause of claim 19, part (a), this clause states an inherent outcome of the method and does not require any further action that that suggested by the references.
Claim(s) 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Najafi (US 2014/0249118) in view of Tabatabaei (IDS 1/22/26) and Safuanovna (RU250222C1) as applied to claims 19, 20, 32, 33, 34, 35, 46, and 47 above, and further in view of Detailed Brush Cytology.
The teachings of Najafi, Tabatabaei and Safuanovna are given previously in this Office action and are fully incorporated here.
The references do not teach testing cells within a cytology brushing sample.
Detailed Brush Cytology (DBC) teaches the brush as an accurate technique for obtaining oral samples for cancer screening (pg. 2). Brush samples remove tissue from all three epithelial layers of the oral mucosa, as opposed to other known methods of collecting samples that only obtain exfoliated oral cells (pg. 5). The brush biopsy is a reliable and immediate way of determining the malignancy or non-malignancy of lesions, thus providing a way of identifying unsuspected oral cancers at early and curable stages (pg. 6).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the instant application to substitute the samples with the cytology brushing samples of DBC, to arrive at the instantly claimed methods of obtaining cells within a cytology brushing sample. One of ordinary skill in the art would have been motivated to substitute the cytology brushing samples of DBC for the samples of Najafi in view of Tabatabaei and Safuanovna, with a reasonable expectation of success, because DBC teaches cytology brushing samples as achieving a more accurate and sensitive method of detecting oral cancers at early and curable states. Furthermore, substituting equivalents, methods of obtaining samples, known for the same purpose, detecting oral cancers, is prima facie obvious, see MPEP 2144.06.
Claim(s) 22 and 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Najafi (US 2014/0249118) in view of Tabatabaei (IDS 1/22/26) and Safuanovna (RU250222C1) as applied to claims 19, 20, 32, 33, 34, 35, 46, and 47 above, and further in view of Oliveira (PTO-892).
The teachings of Najafi, Tabatabaei and Safuanovna are given previously in this Office action and are fully incorporated here.
Oliveira teaches the squamous epithelium lining the oral cavity and that normal oral mucosa is covered by a stratified squamous epithelium (pgs. 709, 710, and 711).
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It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to test squamous epithelium cells from the samples of Najafi in view of Tabatabaei and Safuanovna, to arrive at the instantly claimed methods of squamous epithelial cells affected by LP. One of ordinary skill in the art would have been motivated to test the squamous epithelial cells in or near the OLP because the prior art teaches that OLP can develop into squamous cell carcinoma, and the oral mucosa covered by stratified squamous epithelium cells.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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