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 .
Applicant’s election without traverse of group II, claims 8-13 and 16-26, in the reply filed on 10/2/25 is acknowledged.
Claims 1-7, 14, and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/2/25.
It is noted that applicant did not elect a single species from each category of species set forth in the office action mailed on 4/3/25. Applicant cannot elect all of the species in a single grouping, as in the response filed on 10/2/25. Applicant is required to elect a single species from each of the groupings set forth.
Drawings
The drawings filed on 1/7/22 are objected to because Figures 14 and 15 are not fully legible. 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 Objections
Claims 11-13 and 16-26 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from another multiple dependent claim. See MPEP § 608.01(n). Claims 11-13, 16, and 18-24 are multiple dependent claims that depend from another multiple dependent claim. The remainder of the claims are objected to because they depend from one of these claims. Accordingly, the claims have not been further treated on the merits.
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.
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.
Claim 8 requires for the antisense oligonucleotide to comprise at least 26 base pairs. However, antisense oligonucleotides are single stranded and do not comprise base pairs. Therefore, it is unclear how the antisense oligonucleotide would comprise at least 26 base pairs. The claim language is not definite. Claims 9 and 10 require bases, but depend from a base claim that requires base pairs. It is unclear whether the bases of claims 9 and 10 are an additional limitation or are further limiting the base pairs of claim 8. For purposes of the instant examination, claim 8 is interpreted as the antisense oligonucleotide comprises at least 26 bases rather than base pairs.
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.
The claims are directed to an antisense oligonucleotide that is “capable of binding” at even a single nucleotide to exon 50 of human dystrophin pre-mRNA, wherein binding of the antisense oligonucleotide takes place entirely within the region between +5 and +98 of the pre-mRNA sequence, and wherein the antisense oligonucleotide comprises at least 26 base pairs, at least 27, at least 28 bases, at least 29 bases, or at least 30 bases; or wherein the antisense oligonucleotide consists of 30 bases.
Although the antisense oligonucleotide is at least 26 bases in length, the oligonucleotide is capable of binding at even a single nucleotide to exon 50 of human dystrophin pre-mRNA as long as the binding of the antisense oligonucleotide takes place entirely within the region between +5 and +98 of the pre-mRNA sequence.
The specification does not adequately describe the structure required for the required function. The specification discloses antisense oligonucleotides that are fully complementary to the region between +5 and +98 of the pre-mRNA sequence, which are species that are not representative of the entire claimed genus of antisense oligonucleotides that are capable of binding at even a single nucleotide to exon 50 of human dystrophin pre-mRNA and function by exon skipping. Without further knowledge of the structure required for the function, one would not be able to recognize which antisense oligonucleotides would have the structure require for the function and would not be able to recognize that applicant was in possession of the entire genus claimed at the time of filing.
Additionally, human dystrophin exon 50 pre-mRNA nucleotide sequence by SEQ ID NO, but rather refer to the broad genus of possible sequences. There isn't a single, fixed number, but rather dozens, potentially hundreds or more, distinct human dystrophin pre-mRNA sequences (isoforms) due to extensive alternative splicing and multiple tissue-specific promoters.
The claims encompass antisense oligonucleotides capable of binding to any human dystrophin exon 50 pre-mRNA sequence, as well as encompass any spliced variants or fragment that retains human dystrophin exon 50 pre-mRNA-like activity.
Although the specification discloses antisense oligonucleotides that are fully complementary to a specific human dystrophin exon 50 pre-mRNA sequence, the specification does not describe such agents directed to any other species of human dystrophin exon 50 pre-mRNA to describe the instantly claimed genus of any human dystrophin exon 50 pre-mRNA. Each of the instantly disclosed agents is targeted to a single sequence, although the claims are drawn to any human dystrophin exon 50 pre-mRNA. One of ordinary skill in the art could not make such agents to any human dystrophin exon 50 pre-mRNA without knowledge of the sequence.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See 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 species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, 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:
"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 claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being antisense oligonucleotides that are capable of binding at even a single nucleotide to any exon 50 of human dystrophin pre-mRNA as long as the binding of the antisense oligonucleotide takes place entirely within the region between +5 and +98 of the pre-mRNA sequence and function by exon skipping.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
To achieve the desired function, it appears that the structure is required to have more specificity to a given target. For example, Nedorezova et al. (Theranostics, 2022, Vol. 12, Issue 16, 7132-7157) teach that to ensure tight binding, a typical oligonucleotide gene therapy agent hybridizes to the stretch of 15-25 nucleotides of a unique targeted sequence. However, hybrids of such lengths tolerate one or more mismatches under physiological conditions, the problem known as the affinity/specificity dilemma (abstract). The instant claims read upon binding at a single nucleotide, which would not likely have the structure required for the function.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for oligonucleotides within the instant enormous genus that have the required function. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 102
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 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.
(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.
Claim(s) 8 and 9 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Wilton et al. (WO 2011/057350 A1).
Wilton et al. teach conjugates comprising an antisense oligonucleotide that is capable of biding to a target site in a human exon 50 dystrophin pre-mRNA to induce exon skipping (abstract and page 6). Wilton et al. teach that he antisense oligonucleotide targeting exon 50 binds at +48+74 and resulted in strong and consistent exon 50 skipping (see page 10 and Figure 19). The oligonucleotide is shown at pages 12-13 of Wilton et al. and is 27 nucleotides in length (instant claims 8 and 9).
Therefore, the claims are anticipated by Wilton et al.
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.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wilton et al. (WO 2011/057350 A1).
Wilton et al. teach conjugates comprising an antisense oligonucleotide that is capable of biding to a target site in a human exon 50 dystrophin pre-mRNA to induce exon skipping (abstract and page 6). Wilton et al. teach that he antisense oligonucleotide targeting exon 50 binds at +48+74 and resulted in strong and consistent exon 50 skipping (see page 10 and Figure 19). The oligonucleotide is shown at pages 12-13 of Wilton et al. and is 27 nucleotides in length (instant claims 8 and 9).
The oligonucleotide of Wilton et al. is not 30 nucleotides in length (instant claim 10). However, Wilton et al. disclose antisense oligonucleotides targeting human dystrophin pre-mRNA that are 30 nucleotides in length (page 13). Additionally, Wilton et al. teaches that preferably the antisense oligonucleotide is between 24 and 30 nucleotides in length (page 22).
Therefore, it would have been obvious to design the oligomer of Wilton et al. to be 30 nucleotides in length as a matter of design choice. It would have been obvious to try this length with a reasonable expectation of success given that it is in the preferable size range taught by Wilton et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636