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 the invention of Group 2 (methods of treating including genotype consideration), and the particular gene that is AOX1, in the reply filed on 1/20/2026 is acknowledged.
Claim Rejections - 35 USC § 112 -Indefiniteness
Claims 8-10 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.
Claims 8-10 are unclear over recitation of the limitation “a genetic variance in … AOX1” (as recited in claim 8, as consonant with the election), and the related recitations of “the variance is present in … AOX1” (as recited in claim 9) and “the variance is present in the AOX1 gene” (as recited in claim 10). In the instant case the “variance” is a relative concept (i.e.: the subject gene is changed relative to some reference). But neither the claims nor the specification provide any reference gene sequence, and so it is unclear what gene content is required to present in a subject, or is encompassed, such that the subject patient is a patient that has a genetic variance. The claims may be made more clear in this regard if amended to be directed a particular allele in the patient, such as “the patient has C/C genotype at the rs6729738 single nucleotide polymorphism (SNP) in the AOX1 gene”.
Claim 9 is unclear over recitation of the limitation “a gene associated with Phase I metabolism such as a gene selected from”, because the phrase “such as” appears to indicate that while the recited genes may be examples of genes that are “associated with Phase I metabolism”, it is not clear that the claim is limited to the selection of one of the recited genes. See MPEP 2173.05(h).
Claim Rejection - Improper Markush Grouping
Claims 8 and 9 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 claims, which recites in the alternative a list of independent and distinct genes is improper because the alternatives (i.e.: the different gene sequence) defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
In the instant case each different element is considered to be a method comprising analysis of a different gene sequence to determine the presence of a variation thereof. In the instant case Applicants have elected the particular gene that is AOX1.
The recited alternative elements do not share a single structural similarity, as each method relies on detection of a different polynucleotide sequence (i.e.: a particular gene sequence). Each polynucleotide (i.e.: each different gene) has a different chemical structure in that it consists of a different nucleotide sequence. Each polynucleotide has a different biological activity in that it has a different specificity of hybridization and encodes a different protein each with different biological activity and a different role in the physiology of a cell. Thus, the different elements (e.g.: each different recited gene) do not share a single structural similarity or biological activity. The only structural similarity present is that all of the gene expression products are composed of nucleic acids. The fact that the genes are composed of nucleic acids does not per se support a conclusion that they have a common single structural similarity because the structure of comprising a nucleic acid alone is not essential to the asserted common activity of being related to response to treatment of epilepsy with CBD, as asserted by the instant application. Accordingly, while the different elements are asserted to have the property of having alleles associated with response to treatment of epilepsy with CBD, they do not share a single structural similarity essential to this activity. Here it is clear that any asserted common use does not flow from any broadly ascribed common structure (see MPEP 2117). The asserted common use of being a biomarker for response to treatment of epilepsy with CBD is particular to each different biomarker (i.e.: each particular gene and its specific allele at a particular locus) based on the specific content of the biomarker and not based on some particular common structural feature shared among the different biomarkers.
Note that when the Markush grouping is for alternatives of chemical compounds, the alternatives are regarded as being of a similar nature where the following criteria are fulfilled:
(A) all alternatives have a common property or activity; AND
(B)(1) a common structure is present, that is, a significant structural element is shared by all of the alternatives; OR
(B)(2) in cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
The phrase “recognized class of chemical compounds” means that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention, i.e. each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In the present situation, there is no evidence of record to establish that it is clear from their very nature that the different particular genes recited in the claims are associated with response to treatment of epilepsy with CBD. Additionally, the different biomarkers themselves behave differently, with each having different levels of association (i.e.: different odd ratios; different p-values) with response to treatment of epilepsy with CBD.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
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 8-10 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 claim(s) 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
The requirements for an adequate written description of claimed subject matter is relevant to the claimed methods as they require that “the patient has a genentic variance in … AOX1” (for example as recited in claim 1, as consonant with the election).
The claims encompass any subject organism, and further encompass anything that might be a variation in the AOX1 gene; the claims may encompass any single or multi-nucleotide insertion, deletion or substitution, as well as larger gene amplifications, deletions, or rearrangements. The breadth of the different structures which are generically encompassed by the claims is very large. This is especially true in the instant case where, as noted earlier in this Office Action, the specification does not provide for any standard for comparison to establish that any particular gene content is a variation of any particular reference sequence. The specification provides for only a single particular position of variable content in the AOX1 gene, that is a T allele and a C allele at rs6729738.
Where the structures of the variants encompassed by the claims are generically broad, and there is no disclosed standard of comparison for the determination of a variance, the single disclosed SNP content (i.e.: T allele and a C allele at rs6729738) is not a disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can visualize or recognize the members of the genus. In this regard it is noted that the nature of alleles (i.e.: variable genomic content that may be in a gene of a patient) is that they are variant structures occurring in genomes of individuals from a population; and in the present state of the art, the structure of one allele, such as the disclosed rs6729738, does not provide guidance to the existence or structure of any other alleles.
Considering the breadth of the claims, and the particular teachings of the disclosure, it is the conclusion that the application as filed does not provide an adequate written description of the broadly claimed subject matter.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 8-10 are is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Szarflarski et al (2018) (cited on the IDS of 03/25/2024).
In the rejection of claims as anticipated by the prior art, the practical requirements of the claimed methods are noted. The claims are directed to treating epilepsy in a patient comprising administering CBD to the patient. The claims further set forth that the patient “has a genetic variance in … AOX1” (as recited in claim 8, as consonant with the election). The breadth and clarity of this limitation, which defines the treated subject, has been addressed previously in this Office Action. Here it is again noted that where the claims do not set forth any particular variance in the patient (i.e.: no specific gene content is required to be present), and do not set forth any standard for comparison (i.e.: no reference sequence that would be considered a non-variant gene is required). In this regard it is noted that any AOX1 gene may be the required “genetic variance” depending on what it is compared to. Furthermore, it is noted that the limitation that the patient “has a genetic variance” is not set forth as any practical step of analysis (i.e.: the claims do not require detecting content in a sample from the patient, or comparing a gene sequence from the patient to a reference/control sequence).
With regard to claim 8-10, Szarflarski et al teaches the details of a study including treatment of 607 human patients in which cannabidiol (CBD) was administered for the treatment of treatment‐resistant epilepsies (TREs) (e.g.: Table 1; p.1541- Methods). As described above, these patients meet the limitation of “having a variance in … AOX1”.
Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. The submitted SNP(ss) Details: ss1301205829 (2014) provides a prior art analysis of the allele frequency of the C and T alleles of rs6729738, and demonstrates that the C allele is present in approximately 15% to approximately 44% of human subjects (depending on subpopulation) and the T allele is present in approximately 86% to approximately 56% of human subjects.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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