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
This Office Action is a response to Applicant’s Election filed April 27, 2026.
Claims 1-4, 6-11, 13, 19, 20, 23-26, 35, 37 and 38 are pending in the present application.
Election/Restrictions
Applicant’s election of Group I (claims 1-4, 6-11, 13, 19, 20 and 23-26) in the reply filed on April 27, 2026 is acknowledged. Because Applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Accordingly, claims 35, 37 and 38 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-4, 6-11, 13, 19, 20 and 23-26 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed July 9, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed April 10, 2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed March 23, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed on November 4, 2022 are acknowledged and have been accepted by the Examiner.
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 9 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 pre-AIA the applicant regards as the invention.
The claim is indefinite because it is unclear what is meant by the term, “low cross-reactivities”. The term fails to provide clear boundaries and is otherwise vague and relative. See MPEP 2173.05(b) for further explanation of why the use of relative terminology is indefinite under 35 U.S.C. 112.
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 7 and 8 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.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice..., reduction to drawings..., or 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 function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "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.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed and that applicant was in possession of the claimed genus.
The instant claims are drawn to a polynucleic acid molecule conjugate comprising: an antibody or antigen-binding fragment thereof conjugated to a polynucleic acid molecule that hybridizes to a target sequence of GYS1 mRNA; and wherein the polynucleic acid molecule conjugate mediates RNA interference against the GYS1, wherein the polynucleic acid molecule comprises a sense strand and/or an antisense strand, and the sense strand comprises a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical sequence identity to a sequence selected from SEQ ID NOs: 1-60 or SEQ ID NOs: 121-180 or wherein the polynucleic acid molecule comprises a sense strand and/or an antisense strand, and the antisense strand comprises a sequence having at least 80%, at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% identical sequence identity to a sequence selected from SEQ ID NOs: 61-120 or SEQ ID NOs: 181-240. There is insufficient written description of the polynucleic acid molecules encompassed by the claims. The present Specification discloses polynucleic acid molecules comprising SEQ ID NOs. 1-240, but does not describe sequences with any percent identity that function as claimed to mediate RNA interference against GYS1.
Written description requirement for claims that recite polynucleic acid molecule sequences with the percent sequence identities that function as claimed to mediate RNA interference against GYS1 is not met because the Specification does not provide any description of any variants or what sequences could be modified (added, deleted or mutated) that retain function. Accordingly, the claims encompass using a genus of polynucleic acid molecules which are not adequately described. The claims are rejected because there is insufficient description of the genus of polynucleic acid molecules encompassed by the claims.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “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). It is noted that conception is not achieved until reduction to practice has occurred regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
To satisfy the written description requirement an applicant must describe the invention is such a way as to convey to one skilled in the art that applicant had the invention in his possession when the application was filed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). In cases such as the instant application where a genus is claimed, the specification must contain “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.” Id. at 1350. However, written description requirement for claims that recite polynucleic acid molecule sequences with the percent sequence identities that function as claimed to mediate RNA interference against GYS1 is not met.
The entire genus of polynucleic acid molecule sequences with the percent sequence identities that function as claimed to mediate RNA interference against GYS1 as claimed does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The specification nor the art discloses neither a representative number of species compounds nor any structure/function correlation that would enable one of skill to immediately envision the genus polynucleic acid molecules required to practice the full scope of the invention.
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of polynucleic acid molecules embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
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.
Claim Rejections - 35 USC § 103
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.
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 pre-AIA 35 U.S.C. 103(a) 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 1-4, 6, 10, 11, 13, 19, 20 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/028841 A1 (DYNE THERAPEUTICS INC) 6 February 2020 (2020-02-06) (submitted and made of record on the IDS filed July 9, 2025).
The claims are drawn to a polynucleic acid molecule conjugate comprising: an antibody or antigen-binding fragment thereof conjugated to a polynucleic acid molecule that hybridizes to a target sequence of GYS1 mRNA; and wherein the polynucleic acid molecule conjugate mediates RNA interference against the GYS1. NOTE: The present Specification teaches the human GYS1 sequence is GenBank Accession NM_002103.
DYNE THERAPEUTICS INC teaches a conjugate comprising an anti-transferrin receptor antibody covalently linked to an antisense oligonucleotide targeting the Gys1 mRNA in order to suppress glycogen synthase expression, wherein the conjugation includes a linker. See paragraphs [64]-[65], Examples 4 and 5, claims 17, 32, 40-50, for example. The conjugate is for use in the treatment of Pompe disease. See paragraphs [25], [31], and claim 59, for example. NOTE: The human GYS1 sequence of DYNE THERAPEUTICS INC is GenBank Accession NM_002103.4.
DYNE THERAPEUTICS INC teaches the antisense oligonucleotide targeting the Gys1 mRNA is a modified double-stranded RNA molecule which degrades via the RNA interference (RNAi) pathway. In some embodiments, the modified double-stranded RNA molecule comprises at least one 2' modified nucleotide, at least one modified internucleotide linkage, or at least one inverted abasic moiety. In other embodiments, the modified double-stranded RNA molecule may comprise one or more modified nucleotides (e.g., 2’ -modified nucleotides). In some embodiments, the modified double-stranded RNA molecule comprises a 2'-O-methyl, 2'-fluoro (2'-F), 2'-O-methoxyethyl (2'-MOE), or 2', 4'-bridged nucleotide. In some embodiments, a modified nucleotides is a bridged nucleotide (e.g., selected from: 2', 4'- constrained 2'-O-ethyl (cEt) and locked nucleic acid (LNA) nucleotides).
DYNE THERAPEUTICS INC teaches the overall length of the double-stranded RNA molecules of their invention can vary from about 14 to about 100 nucleotides depending on the type of double-stranded RNA molecule being designed.
DYNE THERAPEUTICS INC teaches the linkers which connect the antibody or antigen-binding fragment thereof to the double-stranded RNA molecule of their invention are maleimide-containing linkers or a sulfosuccinimidyl ester linkers.
DYNE THERAPEUTICS INC teaches the drug (oligonucleotide) to antibody ratio (DAR) is 1, 2, 3 or 4.
DYNE THERAPEUTICS INC teaches in some instances, the double-stranded RNA molecule conjugate of their invention inhibits activity or expression of a target gene by at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90% or at least 95% relative to a control, e.g. baseline level of gene expression prior to treatment.
DYNE THERAPEUTICS INC teaches the double-stranded RNA molecule conjugate of their invention is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times greater or more effective in muscle cells than an amount in non-muscle cells.
Before the effective filing date of the claimed invention, a polynucleic acid molecule conjugate comprising: an antibody conjugated to a polynucleic acid molecule that mediates RNA interference against the GYS1 was known in the art of DYNE THERAPEUTICS INC.
A person of ordinary skill in the art would have been motivated and expected reasonable success to modify the polynucleic acid molecule conjugate of DYNE THERAPEUTICS INC to include nucleic acid modifications that provide for resistance to nucleases for the purpose of increasing the half-life and nucleic acid duplex stability of the polynucleic acid molecule conjugate as taught and suggested by DYNE THERAPEUTICS INC.
Therefore, the subject matter of claims 1-4, 6, 10, 11, 13, 19, 20 and 23-26 is obvious over DYNE THERAPEUTICS INC.
Markush Rejection
Claims 7 and 8 are rejected on the judicially-created 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). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a multitude of polynucleic acid molecules with no common searchable core. The hundreds of nucleotide sequences have no common structure other than being nucleic acid sequences. The specific activity of each polynucleic acid molecule is dependent upon the specific sequence of nucleotides.
Furthermore, the Markush groupings of the SEQ ID NOs listed in claims 7 and 8 are 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: Each of the SEQ ID NOs is different and targets a different region of the GYS1 gene (NM_002103). See Tables 11 and 12 of the present Specification. Each polynucleic acid molecule sequences has its own structure based on its sequence, so while they share a common use, the alternatives do not share a common structure.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be 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, i.e., 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.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer 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 structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean 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. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific polynucleic acid molecule is dependent upon the specific sequence of nucleotides. There is no expectation that any one of the nucleotide sequences as claimed can be substituted for any of the other with a completely different sequence with the expectation of the same activity.
Furthermore, the Patent Office does not have the resources to search hundreds of sequences in one application and perform the corresponding examination.
See 37 CFR 1.141(a),
The examination guidelines determined that “up to ten sequences” are reasonable depending upon the circumstances. Each of the instant sequences are structurally unique, each comprising a distinct sequence of nucleotides, each having no common structural core. To search for more than ten of the sequences in the same application would present an undue search and corresponding examination burden. See Examination of Patents with Nucleotide Sequences - OG Date: 27 March 2007, wherein the document explains the rescission of the 1996 Notice that allowed up to ten independent and distinct sequences for search and examination in an application.
Art Made of Record but not Relied Upon
WO 2015179741 A1 disclose antisense oligonucleotides (AONs) for modulating the expression of glycogen synthase (NM_ 002103.4).
U.S. Patent No. 12370264 B1 teach conjugates comprising an anti-transferrin receptor antibody linked to an oligonucleotide and method of delivering oligonucleotides to a subject for treating Pompe disease.
U.S. Patent No. 12239710 B2 teach conjugate molecules comprising dsRNA molecules targeted to GYS1 (NM_ 002103) and linked to an antibody or antigen-binding fragment. U.S. Patent No. 12239710 teach a particular dsRNA molecule which comprises SEQ ID NO: 36 (sense strand) and SEQ ID NO: 96 (antisense strand) of the present invention. See sequence alignments below:
The earliest priority date for U.S. Patent No. 12239710 is 04/14/2021.
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Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 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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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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