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 .
Claims 1-20 are pending.
Claim Objections
Applicant is advised that should claim 2 be found allowable, claim 4 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim 2 of instant application recites “…decrease a GCDH protein activity in the subject” while claim 4 recites “…decrease GCDH protein enzyme activity in the subject”. Both claims are drawn to the same invention because GCDH is an enzyme.
Drawings Objections
The drawings are objected to because the text in the drawings (Figs 1-10) is too small, blurry or too low in resolution. This makes reader hard to read the content of the drawing and to permit satisfactory reproduction.
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 USC § 112(a) – 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 1-20 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. This is a written description rejection.
Claims 1-20 encompass a compound that modulates a glutaryl-CoA dehydrogenase (GCDH) protein activity.
The broad claims encompass the large genus: any compounds that modulate the protein activity of GCDH gene. The specification of instant application indicates that compound comprises a ribonucleic acid.
MPEP 2163.ll.A3.(a).(i) states, "whether the specification shows that applicant was in possession
of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the 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."
For claims drawn to a genus, MPEP 2163.II.A3.(a).(ii) states, "written description requirement
for a claimed genus may be satisfied through sufficient description of a representative number of species" where "representative number of species' means that the species which are adequately
described are representative of the entire genus. Thus, when there is substantial variation within the
genus, one must describe a sufficient variety of species to reflect the variation within the genus."
Claim 1 of instant application recites “…compound wherein the compound modulates a GCDH protein activity”. The specification of instant application teaches that the compounds comprise a nucleic acid and more specifically ribonucleic acid (0020). However, this is not a limiting definition. In the art, inhibiting compounds can also be small molecules, polypeptides like antibodies, small peptides and aptamers. Thus, the genus of possible compounds could include nearly any biological molecule, which is an extremely vast and diverse genus. For the reasons described below, except for nucleic acids that have 100% identity to a DNA open reading frame, a mRNA transcript of the recited gene, or expression vectors that encode the recited gene, the genus of compounds that modify, inhibit and/or activate expression or activity of GCDH genes is not sufficiently described.
The Specification provides no structural information about peptides, small molecules, polymers,
aptamers, or antibodies that function to modulate the expression of recited gene. The specification identifies the compounds primarily by their desired functional result – i.e., compounds that modulate GCDH activity– and provides nucleic-acid species, including RNA, miRNA, shRNA, siRNA, and specified GCDH-targeting sequences. However, the specification does not provide a representative number of compounds across the full breadth of the claimed genus that modulate GCDH protein activity, nor does it identify structural features common to the full genus that would reasonably demonstrate possession of the claimed genus as a whole.
No antibody, polymer, peptide, small molecule, or aptamer structure is recited that correlates to
the claimed function of modulating GCDH gene. A definition by function does not suffice to define the genus because it is only an indication of what the antibody, polymer, peptide, small molecule, or aptamer does, rather than what it is. To provide adequate written description and evidence of possession of the claimed antibody, polymer, peptide, small molecule, or aptamer genus, the instant
specification in view of the art must structurally describe representative antibody, polymer, peptide,
small molecules, or aptamer that function as a modulator of protein activity or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California V. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
Finer (US6410254B1) teaches that modulators of a target protein include both agonists and antagonists and that modulation of target protein activity may include increasing and decreasing the activity of the target protein (column 10, line 33-39). Finer further teaches that the candidate bioactive agents or compounds may comprise proteins, oligopeptides, small molecules, polysaccharides, and polynucleotides and may encompass numerous chemical classes and structural forms (column 10, line 48-55). Another art by Kole et al. 2012 (Nature reviews Drug discovery, 11:125-140, “Kole”) demonstrates that the RNA-targeting reagents vary in structure and are diverse in structure-function relationship. Kole describes distinct reagents, including siRNAs, antisense oligonucleotides, splice-switching oligonucleotide, translation-suppression oligonucleotides, and external guide sequences and these reagents do not share common structural characteristics. Although these reagents can recognize target through sequence-specific base pairing, they differ in structure, mechanism of action, and the state of gene expression at which they act. For example, siRNA and antisense oligonucleotide can induce enzymatic degradation of target mRNA, whereas splice-switching oligonucleotides acts on pre-mRNA to alter splicing and translation-suppression oligonucleotides inhibit translation process. Table 1 of Kole describes multiple reagents, their mechanism of action, outcome, and state of gene expression at which they act (pre-mRNA or mRNA).
Given the lack of representative examples to support the full scope of the modulators of GCDH protein activity, and lack of reasonable structure-function correlation with regards to the unknown sequences of an antibody, polymer, peptide, small molecule, or aptamer that can modulate the function of GCDH gene products, the specification does not provide an adequate written description of "compounds" that modulates the protein activity of GCDH gene that is required to practice the claimed invention.
Claims 2-4 and 16-20 do not limit the genus of compounds and are not sufficiently described for the reasons recited above for claim 1.
Claims 5-6 limit the genus “compounds” to nucleic acids and RNAs. RNAs can act as aptamers. As indicated above for claim 1, the Specification does not disclose the structure of DNA or RNA that can act as an aptamer to bind GCDH and inhibit its activity. As such, claims 5-6 still encompass compounds for which there is insufficient description and therefore are rejected.
Claims 7-9 limit the genus to inhibitory nucleic acids that are miRNA, shRNA and siRNAs. The Specification only provides the sequence/structure of inhibitory RNAs that hybridize to the GCDH mRNA. However, the claims still encompass any siRNA/shRNA/miRNA that could act upstream of GCDH to regulate the expression of GCDH. Applicants do not disclose, and the prior art does not provide genes that are known to regulate GCDH expression. As such, the skilled artisan could not predict what the structure of additional siRNA/shRNA/miRNAs would be.
Claims 10-15 limit the genus to ribonucleic acid sequence that is “at least about 80%”, “at least about 90%”, and “at least about 100%” to SEQ ID NOs 13 and 14. Each of the SEQ ID NOs 13 and 14 are 21 nucleotide long. Claims 10 and 11 encompasses up to 4 nucleotide substitution relative to SEQ ID NOs 13 and 14 to meet the criteria of being 80% identical. Accordingly, 21 nucleotide sequence having 80% identify encompasses approximately 522,649 possible sequences. Similarly, claims 12 and 13, which required at least about 90% identity, encompass approximately 1954 possible sequences. For claims 14 and 15, the claims recite “about” 100% identical and specification does not provide the limiting definition of “about”. Therefore, it is interpreted as ± 10%. Claims 14 and 15 have essentially the same sequence scope as claims 12 and 13.
Claim Rejections - 35 USC § 112(a) – Enablement
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the treatment of melanoma using GCDH-modulating nucleic acid siRNA, does not reasonably provide enablement for the treatment of any conditions or disease by using any compounds in any subjects. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant factors are indicated below:
The breadth of the claim: the claim as currently drafted is broad and it encompasses a method of treating any conditions, in any subject, by administrating therapeutically effective amount of any compounds which modulates the protein activity of GCDH gene. Consequently, the breadth of this claim is broad.
The nature of the invention: The claims are drawn to methods of conditions, which encompasses a very large and etiologically diverse genus of diseases, some of which are recited in claims 16-20. The claims also recite administering to a subject a therapeutically effective amount of a compound that modulates the protein activity of a GCDH gene. The structures of such compounds are not sufficiently described for the reasons recited in the previous section. Nevertheless, even if they were sufficiently described, their administration would also encompass an extremely large genus that would require different routes, different target cells, and whose effects would vary greatly depending on the gene targeted, the pathway the gene is involved in, and the transcriptional state and environment of the cells. Accordingly, enablement of the method requires one skilled in the art to be able to treat the genus of “conditions” by administering a large and diverse genus of "compounds" that modulates the protein activity of GCDH gene in any subjects. Therefore, to make such a claimed method perform as described, there will be undue burden as it will require undue experimentation.
The amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention based on the content of the disclosure: the applicant has not provided sufficient direction to practice the full scope of the claimed invention. The enablement requirement is met when the specification teaches a person of ordinary skill in the art how to make and use the full scope of the claimed invention without undue experimentation. In the present case, the specification does not provide sufficient guidance or representative working examples to enable the full scope of the claimed method of treating any conditions by administrating compounds wherein the compounds modulate the GCDH protein activity. The working examples of the present application demonstrate GCDH inhibition in a limited experimental context, particularly through the use of siRNA molecule, in melanoma models (examples 2-6). Examples 2-6 collectively demonstrated that inhibition or knockdown of GCDH using particular RNA-based reagents can reduce GCDH expression/activity and produce antitumor effects through NRF2/UPR-dependent cell-death mechanism in melanoma models. The examples therefore provide support for practicing the invention with GCDH modulating agents for the treatment of Melanoma. However, the working examples do not demonstrate the full scope of the claimed invention. In particular, the examples do not demonstrate the treatment of the broad range of “conditions” encompassed using broad range of “compounds” encompassed by claim 1. Thus, working examples demonstrate only particular species within the broad genus encompassed by the claims and do not provide sufficient basis for concluding the full claimed scope can be practiced without undue experimentation.
The state of the prior art: The state of the prior art demonstrated that GCDH protein activity was recognized as being associated with multiple different disease conditions. For example, Mao (WO2002040523A1, published 23 May 2002) teaches that GCDH polypeptide, and their agonists, antagonists, and inhibitors may be used in the treatment of various diseases, including malignant tumors, adrenal deficiency, skin diseases, various inflammatory diseases, HIV infection, immune diseases, cancer, developmental diseases, and hematological diseases (6th paragraph of page 43, last paragraph of page 39). However, Mao does not actually demonstrate treating any conditions with the inhibitor. Thus the teaching is prophetic and does not enable the skilled artisan to treat any disease associated with the GCDH inhibitor. Furthermore, the state of the prior arts also demonstrates that compounds capable of modulating protein activity encompass structurally and functionally diverse agents. For example, Finer (US6410254B1) teaches that modulators of a target protein include both agonists and antagonists and that modulation may comprise an increase, decrease, or change in the type of activity of the target protein (column 10, line 33-39). Finer further teaches that the candidate bioactive agents may comprise proteins, oligopeptides, small molecules, polysaccharides, and polynucleotides and may encompass numerous chemical classes and structural forms (column 10, line 48-55).
The breadth of the claimed invention also encompasses administration of GCDH-modulating compounds to subjects in whom GCDH activity is present in normal, healthy tissues. GCDH is an important enzyme and plays major role in many physiological activities. Thus, reducing GCDH activity in non-target or healthy tissue could potentially produce unintended metabolic effects. More generally, gene therapy approaches present potential risks from immune response, vector distribution to non-target tissue, and on-target/off-target effects. The specification of the instant application does not provide sufficient guidance across the full scope of the claims regarding the appropriate compound, dose, route of administration, degree of GCDH modulation, tissue specificity, or therapeutic window necessary to achieve therapeutic effect while avoiding adverse effect in healthy tissue. Therefore, undue experimentation would be required to determine which GCDH-modulating agents and treatment conditions could safely be used across the full range of conditions and subjects encompassed by the claims.
Thus, in view of prior art, and in the light of specification, it is highly unpredictable how the skilled artisan would treat the genus of conditions using the genus of compounds that modulates the activity of GCDH gene.
MPEP 2164.01(a) states that “a conclusion of lack of enablement means that, based on the
evidence regarding each of the above factors, the specification, at the time the application was filed,
would not have taught one skilled in the art how to make and/or use the full scope of the claimed
invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510,
1513 (Fed. Cir. 1993)”. That conclusion is justified by our analysis presented above. The Wands Factors
have been analyzed which also supported undue experimentations would be required to practice the
invention as claimed due to the amount of experimentation necessary, state of the prior arts and its predictability, the high level of skill required to practice the alleged invention, and the limited amount of guidance provided by the applicant in the form of varied working examples in the specification.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 16, and 17 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Mao (WO2002040523A1, published 23 May 2002).
Note: the citation of page numbers and paragraph of Mao is from English translation version downloaded from google patent. The Mao document and English translation from google patent is attached as foreign reference document.
Mao teaches human glutaryl coenzyme A dehydrogenase (GCDH) and describes GCDH as an enzyme and abnormal GCDH expression as being associated with diseases. Mao teaches a method of applying the polypeptide for the treatment of various kind of diseases (Abstract).
Regarding claim 1, Mao specifically teaches a class of compounds that mimic, promote, antagonize or inhibit the activity or expression of human GCDH (claim 11). Mao further teaches that the compound is an antisense sequence (claim 12).
Page 40 (paragraph 9 and 10) of Mao teaches that inhibitors or antagonist increase or decrease protein activity of human GCDH.
Mao teaches that the invention can be used to treat or prevent diseases related to human GCDH and administration of appropriate doses of antibodies can stimulate or block the production or activity of human GCDH (paragraph 7 of page 44).
Regarding claim 2 and 3, Mao teaches that antagonist or inhibitor can increase or decrease protein activity of human GCDH (paragraph 10 of page 40). Mao teaches that agonist when combined with human GCDH, caused a change in the protein to regulate the activity of the protein (see paragraph 8 of page 40). Claim 11 of Mao teaches that compounds mimic or regulate the activity or expression of a polypeptide.
Regarding claim 4, Mao teaches that GCDH as an enzyme that catalyzes the oxidative decarboxylation of flutaryl-CoA to butyryl-CoA and carbon dioxide (see second paragraph of page 39). Mao further teaches antagonists of human GCDH and states that antagonist may bind to human GFDH and eliminate its function (see page 43). Because GCDH is itself an enzyme, blocking the activity of GCDH protein corresponds to decreasing the claimed GFDH protein activity.
Furthermore, Mao also teaches that antagonist or inhibitor can increase or decrease protein activity of human GCDH (paragraph 10 of page 40).
Regarding claim 5, Mao teaches that antagonists and inhibitors, which are compounds, may include proteins, nucleic acids, carbohydrates or any other molecule that can bind to human GCDH (see paragraph 9 of page 40).
Regarding claim 6, Mao teaches the GCDH-inhibition compound comprise an antisense sequence (see claim 12 of Mao). Mao further expressly teaches inhibition of human GCDH using antisense RNA and DNA (see paragraph 12 of page 44). Thus, the antisense GCDH inhibitor disclosed by Mao encompasses an RNA molecule. Accordingly, Mao teaches the limitation of claim 6 requiring that the compound comprise a ribonucleic acid (RNA).
Regarding claim 16, Mao teaches that the invention is about method of treating disorders related to excessive cell proliferation, such as various cancers (See page 43).
Regarding claim 17, Mao teaches gene-chip expression analysis in many cancer tissue and cell lines including liver cancer and prostate cancer. Mao teaches that the expression profile of polypeptide of present invention is very similar to that of human GCDH (see fourth paragraph of page 39), indicating that two have similar biological function. Mao teaches that GCDH antagonists can prevent and treat disorders associated with excessive cell proliferation, including various cancers (see page 43). Thus, Mao teaches i) GCDH expression in cancer including liver cancer and prostate cancer, and ii) therapeutic use of GCDH inhibitors for the treatment of cancers. Therefore, Mao teaches the limitation of claim 17.
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.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over by Mao (WO2002040523A1, published 23 May 2002) as applied to claims 1-6, 16, and 17 above, and further in view of Hiroyuki (WO2021107005A1, published 03 June 2021, cited in IDS#005).
Regarding claims 7-9, Mao does not teach that the ribonucleic acid comprises microRNA, short hairpin RNA (shRNA), and small interfering RNA (siRNA).
However, Hiroyuki teaches therapeutic agents or compounds that suppress the expression or function of at least genes selected from a group consisting of 80 genes (abstract). Furthermore, Hiroyuki listed the 80 genes that can be suppressed by the compounds or agents including Glutaryl-CoA Dehydrogenase (GCDH) (claim 1 and page 47).
The active ingredients that suppress the expression of genes comprise nucleic acid polymers. Hiroyuki also teaches that nucleic acid polymers comprise RNA interference (RNAi). Hiroyuki further teaches that RNAi can be shRNA, siRNA, and miRNA (see paragraph 8 and 9 of page 51).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Mao by using the ribonucleic acid such as microRNA, shRNA, and siRNA as taught by Hiroyuki. A person of ordinary skill in art would have been motivated to do so because Hiroyuki expressly identifies GCDH as a gene whose expression or function can be suppressed by RNAi and teaches that RNAi nucleic-acid polymers may comprise miRNA, shRNA, or siRNA. Such modification would involve selecting a known RNAi technique for carrying out the GCDH inhibition as taught by Mao and would have had a reasonable expectation of success because RNAi was known in the art to suppress target mRNA expression.
In view of the foregoing, claims 7-9 taken as a whole would have been prima facie obvious before the effective filing date.
Claims 10, 12, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over by Mao (WO2002040523A1, published 23 May 2002) as applied to claims 1-6, 16, and 17 above, and further in view of GenBank (XM_003760670.4, GCDH transcript variant X1, mRNA, https://www.ncbi.nlm.nih.gov/nuccore/XM_003760670.4, retrieved 14 September 2026) and Schramm (siRNA design including secondary structure target site prediction, Application Notes, 2005).
Claims 10, 12, and 14 of instant application recite that the sequence of ribonucleic acid that is at least about 80% (claim 10), about 90% (claim 12), and about 100% (claim 14) identical to SEQ ID NO: 13. The claimed sequence is a ribonucleic acid, particularly siRNA.
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GeneBank XM_003760670.4 teaches the mRNA sequence of GCDH which is 100% identical to the claimed SEQ ID NO: 13. See below for sequence alignment.
Schramm teaches a method for designing siRNA directed to a target mRNA, including analysis of the target sites and secondary structure to identify potentially effective siRNA sequences. Schramm describes conventional siRNA duplexes having a 19-mer sequence with symmetric 2-3nt 3’ overhand (under “RNAi mechanism and history” section). Schramm further teaches that siRNA antisense strand guides RNA-induced silencing complex (RISC) to the target mRNA, resulting in endonucleolytic cleavage (under “RNAi mechanism and history” section).
It would have been obvious to try the targeting sequence of the claimed siRNA molecule because there are finite number of predictable solutions for the target sequence. Schramm teaches that siRNA design involves selecting target sites within an mRNA sequence and describes conventional siRNA duplexes having a 19-mer sequence with symmetric 2–3-nt 3′ overhangs. GenBank XM_003760670.4 is 1994 bp in length. Thus, there are only 1994-19=1975 predictable targeting sequences with 100% identity to the target sequence. Accordingly, an artisan would have been motivated to select a suitable siRNA target within the disclosed GCDH mRNA, including the sequence corresponding to SEQ ID NO: 13, using the known siRNA-design techniques taught by Schramm, with a reasonable expectation of success.
In view of the foregoing, claims 10, 12, and 14 taken as a whole would have been prima facie obvious before the effective filing date.
Claims 11, 13, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over by Mao (WO2002040523A1, published 23 May 2002) as applied to claims 1-6, 16, and 17 above, and further in view of GenBank (KU297256.1, Homo sapiens isolate case 16 GCDH, mRNA, https://www.ncbi.nlm.nih.gov/nuccore/KU297256.1, retrieved 14 September 2026) and Schramm (siRNA design including secondary structure target site prediction, Application Notes, 2005).
Claims 11, 13, and 15 of instant application recite that the sequence of ribonucleic acid that is at least about 80% (claim 11), about 90% (claim 13), and about 100% (claim 15) identical to SEQ ID NO: 14. The claimed sequence is a ribonucleic acid, particularly siRNA.
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GeneBank KU297256.1 teaches the mRNA sequence of GCDH which is 95.2% identical to the claimed SEQ ID NO: 14. See below for sequence alignment -
Schramm teaches a method for designing siRNA directed to a target mRNA, including analysis of the target sites and secondary structure to identify potentially effective siRNA sequences. Schramm describes conventional siRNA duplexes having a 19-mer sequence with symmetric 2-3nt 3’ overhand (under “RNAi mechanism and history” section). Schramm further teaches that siRNA antisense strand guides RNA-induced silencing complex (RISC) to the target mRNA, resulting in endonucleolytic cleavage (under “RNAi mechanism and history” section).
The alignment shows that 20 of 21 nucleotide of SEQ ID NO: 14 are identical to the corresponding GCDH mRNA sequence disclosed in KU297256.1, corresponding to 95.2% sequence identity. Thus, to the extent that the term “about 100% identical” encompasses approximately 95% sequence identity, as recited in claim 15, the disclosed GCDH sequence falls within the claimed “about 100% identity” limitation.
It would have been obvious to try the targeting sequence of the claimed siRNA molecule because there are finite number of predictable solutions for the target sequence. Schramm teaches that siRNA design involves selecting target sites within an mRNA sequence and describes conventional siRNA duplexes having a 19-mer sequence with symmetric 2–3-nt 3′ overhangs. GenBank KU297256.1 is 1897 bp in length. Thus, there are only 1897-19=1878 predictable targeting sequences with about 95% identity to the target sequence. Accordingly, an artisan would have been motivated to select a suitable siRNA target within the disclosed GCDH mRNA, including the sequence corresponding to SEQ ID NO: 14, using the known siRNA-design techniques taught by Schramm, with a reasonable expectation of success.
In view of the foregoing, claims 11, 13, and 15 taken as a whole would have been prima facie obvious before the effective filing date.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SURAJ SAPKOTA whose telephone number is (571)270-0842. The examiner can normally be reached Monday-Thursday 7am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram R Shukla can be reached at (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Suraj Sapkota
Patent Examiner
AU 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
