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
Election/Restrictions
Applicant's election without traverse of Group I, claims 141 and 189-214 in the reply filed on 10/01/2025 is acknowledged.
Status of the Application
Claims 141 and 189-227 are pending. Claims 141 and 189-214 are currently under examination. Claims 215-227 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
The submission of the Information Disclosure Statements on 10/01/2025 and 10/06/2023 is in compliance with 37 CFR 1.97. The information disclosure statements have been considered by the examiner and signed copies have been placed in the file.
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.
Claim 206 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 206 is indefinite because the word "optionally" in line 2 renders the claim indefinite because it is unclear whether the limitations following the word are part of the claimed invention. See MPEP § 2173.05(d).
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 141, 189-192, 198, 206-208, 213 and 214 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hornstein et al. (US 20180064748), Sciabola et al. ("PFRED: A computational platform for siRNA and antisense oligonucleotides design." PLoS One 16.1 (2021)), Davidson et al. (Patent No. 8,258,286) and Klein et al. (Molecular Therapy vol. 16 no. 1, 89–96 Jan. 2008).
Regarding claims 141 and 189-192, Hornstein et al. teach Motor neuron diseases belong to a group of neurological disorders such as Parkinson’s disease and Alzheimer’s disease and teach methods of providing treatment by inhibiting expression of genes known to be associated with the disease such as Grick2 (see 0002-0013). Horstein et al. teach Grik2 has a nucleic acid sequence set forth in Genbank accession NM_021956 (0085). Horstein et al teach inhibition of gene expression using methods such as miRNA, RNAi or antisense inhibitors (see 0086, 0095-101). Horstein et al. do not teach a nucleic acid sequence having SEQ ID No. 77 or 80 or a double stranded sequence having a guide sequence of SEQ ID Nos. 77 or 80 and a passenger stand sequence having sequence of SEQ ID Nos. 798 and 799 respectively. Horstein et al. do not teach the nucleic acid sequences in expression cases, vectors or teach pharmaceutical compositions.
The prior art of Sciabola et al. teach a computational platform for siRNA and antisense oligonucleotide design that target a specific gene of interest (see abstract). Sciabola et at. teach all that is required is input of an accession number for the target genes and the output is sequences with any number of desired properties (see page 2).
It would have been obvious to try making the claimed nucleic acid sequences having at least 85% sequence identity to the claimed sequences using the computational tool taught by Sciabola. Because Horstein et al. teach the target gene Grik2 is known to be associated with motor neuron diseases and teach inhibition of Grik2 gene expression as a method of treatment, there is a design need to develop inhibitory oligonucleotide such as an antisense or siRNA to target Grik2. Moreover there is a finite number of identifiable and predicable sequences that can be made for inhibition of expression of the Grik2 gene (MPEP 2143 KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007)).
Regarding claims 198, 206, 207 and 213, the prior art of Davidson et al. teach using inhibitory nucleic acids such as siRNA in pharmaceutical compositions, expression cassettes and vectors such as AAV (col. 11, 12, col. 36 line 60-col. 38). It would have been obvious to use the nucleic acid made above in a compositions for delivery in an expression cassette and vector.
Regarding claim 208, Klein et al. teach AAV serotypes like AAV9 or AAVrh10 are much more efficient compared to the other AAV serotypes, particularly in mouse brain tissue (see page 89). One of skill in the art would have wanted to use these AAV serotypes in making a vector for treatment of motor neuron diseases.
Regarding claim 214, a kit is considered obvious in view of a teaching of the compound because a kit merely contains the compound and instructions for use. It is noted that claims directed to a kit are considered obvious over the composition. USPTO personal need not give patentable weight to printed matter absent a new and unobvious functional relationship between the printed matter and the composition (see MPEP 2106.01). It is considered obvious to formulate the product into a kit with instructions for use.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description
Claims 141 and 189-214 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 pre-AIA 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 by him. The courts have stated:
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 invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that 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.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
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: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed 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.
The claims are drawn to a genus of guide sequences, passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors having 85% or more sequence identity to the claimed sequences with the function of targeting Grik2 and reducing expression in cells and in mice.
The specification describes guide sequences, passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors having 100% sequence identity to the claimed sequences that when assembled in an expression vector had the function of inhibiting expression of Grik2 in cells and in mice.
The genus of the expression vectors comprising 85% or more sequence identity to each of guide sequences, passenger sequences, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes encompasses a vast number of different sequences assemble in differently sized expression vectors.
The specification describing only vectors comprising 100% sequence identity to the claimed sequences does not indicate what distinguishing characteristics that are concisely shared by the members of the broad genus claimed that would convey to one of skill in the art that these sequences represent the entire genus. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
The prior art of Fakhr et al. ("Precise and efficient siRNA design: a key point in competent gene silencing." Cancer gene therapy 23.4 (2016): 73-82) is a reference stating there has been some controversy over the best length for siRNA functionality as some have worked with siRNA 19 nucleotides in length with efficient silencing and others in the field have found good results using siRNAs 21 to 29 nucleotides in length (see page 75 first para.). Fakhr et al. states shorter siRNAs may lead to an unspecified binding of the target but others have found siRNA 19 to 25 nucleotides have shown the same efficiency in silencing. This demonstrates there is some unpredictability in gene silencing using differently sized inhibitory molecules and one of skill in the art would not be able to distinguish the functional species of a vector having 85% identity to the guide strand, passenger strand along with85% identity miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors from the non-functional species.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant comprising a vast number of sizes of the sequences in the vector, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the 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" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every size of guide strands, passenger strands, miRNA loop sequences, 5’ and 3’ flanking regions, promoter sequences, expression cassettes and vectors. The description requirement of the patent statute 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 369,372-372 (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 inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Closest prior art
A search of the sequence data base did not reveal sequences having 85% or more identity to SEQ ID Nos. 767, 759, 760, 766, 765, 685, 792, 815 or 811 in polynucleotides comprising a 5’-inverted repeat sequence, a promoter, a polyA sequence, a stuffer and a 3’ inverted terminal repeat sequence.
Davidson et al. teach making miRNA shuttle vectors that express a therapeutic RNA molecule wherein the shuttle has 5’ and 3’ flanking regions, a guide strand, a passenger strand and a miRNA loop having SEQ ID No. 184 that is identical to claimed SEQ ID No. 761. (see col. 2-3). Davidson et al. does not teach or make obvious the claimed polynucleotide compositions comprising a guide strand and passenger strand as claimed along with 5’-inverted repeat sequence, a promote, a polyA sequence, a stuffer and a 3’ inverted terminal repeat sequence.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636