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 January 27, 2026.
Claims 1-18 are pending in the present application.
Election/Restrictions
Applicant’s election of Group I (claims 1-15) in the reply filed on January 27, 2026 is acknowledged. Applicant’s species election of an siRNA comprised of SEQ ID NOs: 20 (antisense) and 50 (sense); and PDoV1 (SEQ ID NO:130) in the reply filed on January 27, 2026 is also 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Accordingly, claims 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 1-15 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed March 7, 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 March 7, 2023 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 6 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.
Claim 6 is rejected because it recites elements that lack an antecedent basis. Specifically, claim 6 recites the terms “X” and “Z” in Structure I or II. The terms “X” and “Z” are not defined in the claim. As such, the claim is rejected for a lack of antecedent basis. Appropriate correction is re quired.
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 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 12054714 B2 (SIRNAOMICS, INC.) in view of U.S. Patent No. 8273869 B2 (Alnylam Pharmaceuticals Inc.).
The claims are drawn to a chemical construct comprising a Peptide Docking Vehicle (PDoV) covalently linked to (a) a targeting moiety, and (b) a therapeutic nucleic acid, wherein said therapeutic nucleic acid inhibits expression of PCSK9 gene, and wherein the PDoV comprises multiple repeating units of histidine and lysine.
Regarding claims 1, 3 and 15, SIRNAOMICS teach a chemical construct comprising a Peptide Docking Vehicle (PDoV) covalently linked to (a) a targeting moiety, and (b) a therapeutic nucleic acid, wherein the therapeutic molecule is an siRNA, and wherein the PDoV comprises multiple repeating units of histidine and lysine. See Abstract and SUMMARY OF THE INVENTION, for example.
Regarding claims 2 and 13, SIRNAOMICS teach the targeting moiety is GalNAc. See Figure 1, for example.
Regarding claim 5, SIRNAOMICS teach the PDoV construct of their invention comprises an endosomal release motif. See FIELD OF THE INVENTION.
Regarding claim 6, SIRNAOMICS teach a PDoV construct comprising Structures I or II of the present invention. See SIRNAOMICS, wherein the construct of their invention may have one of the where: type X sites are used to conjugate the targeting ligands; Type Y sites are used to conjugate the oligonucleotide, and X and Y can be the same or different; A is a peptide sequence of H, K, R, HH, HHH, HHHH (SEQ ID NO: 1), HHK, HHHK (SEQ ID NO: 2) or any other endosomal releasing short peptide containing up to about 5 amino acids; B is a peptide sequence of H, K, R, HH, HHH, HHHH (SEQ ID NO: 1), HHK, HHHK (SEQ ID NO: 2), or any other short peptide containing up to about 5 amino acids, any other amino acid or combination of amino acids with a linker; D is an oligonucleotide; RL is ligand; and RS is a linker to the oligonucleotide.
Regarding claim 7, SIRNAOMICS teach a PDoV construct comprising SEQ ID NO: 130 of the present invention. See SIRNAOMICS, Sequence 60.
Regarding claim 14, SIRNAOMICS teach a GalNAc Peptide Docking Vehicle (G-PDoV) comprising SEQ ID NO: 135 of the present invention . See SIRNAOMICS, Sequence 3 and Figure 1, for example.
Regarding claim 8, SIRNAOMICS teach the targeting moiety comprises a ligand covalently linked to said PDoV construct via a linker of formula III or IV of the present invention. See claim 3.
Regarding claim 9, SIRNAOMICS teach that the therapeutic nucleic acid of their invention comprises at least one nucleotide chemically modified at the 2′ position with, for example, 2′-OCH3, 2′-F, or 2′-O-MOE.
Regarding claim 10, SIRNAOMICS that the therapeutic nucleic acid of their invention is an siRNA molecule comprising one or more chemically modified nucleotides selected from the group consisting of a phosphorothioate diester or phosphorodithioate.
Regarding claim 12, SIRNAOMICS teach therapeutic nucleic acid of their invention is linked to the PDoV construct via the 5' or 3' position of a nucleotide or nucleoside in said nucleic acid, and wherein the linker is an aliphatic chain, a polyethylene glycol chain, a hydrophilic chain or a hydrophobic chain. See SIRNAOMICS @ Linkers Between RNAi and Peptide.
SIRNAOMICS do not teach the therapeutic nucleic acid inhibits expression of PCSK9 gene.
Regarding claims 4 and 11, Alnylam teach siRNA nucleic acids that inhibit the expression of PCSK9 gene as therapeutic nucleic acids. Alnylam teach a particular siRNA nucleic acid which comprises SEQ ID NO: 14 of the present invention.
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Before the effective filing date of the claimed invention, a chemical construct comprising a Peptide Docking Vehicle (PDoV) covalently linked to (a) a targeting moiety, and (b) a therapeutic nucleic acid, wherein the therapeutic molecule is an siRNA, and wherein the PDoV comprises multiple repeating units of histidine and lysine was known and taught in the prior art of SIRNAOMICS.
It would have been obvious and one of skill in the art would have been motivated to modify the teachings of SIRNAOMICS to include a PCSK9 siRNA comprising SEQ ID NO: 14 of the present invention since SIRNAOMICS taught a peptide docking vehicle for targeted nucleic acid delivery and Alnylam taught the desire to use gene therapy to target PCSK9 gene and protein expression.
Therefore, the subject matter of claims 1-15 is obvious over SIRNAOMICS in view Alnylam.
Markush Rejection
Claims 4 and 11 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 siRNA therapeutic nucleic acids with no common searchable core. The dozens of nucleotide sequences have no common structure other than being nucleic acid sequences. The specific activity of each siRNA molecule is dependent upon the specific sequence of nucleotides.
Furthermore, the Markush groupings of the siRNA SEQ ID NOs listed in claims 4 and 11 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 on the PCSK9 mRNA. Each sequence 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 siRNA 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.
The Patent Office does not have the resources to search dozens 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. Furthermore, 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.
Non-Statutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12054714 B2 (hereinafter, “’714 Patent”) in view of U.S. Patent No. 8273869 B2 (Alnylam Pharmaceuticals Inc.). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims embrace and encompass claims 1-12 of the ‘714 Patent.
The claims of the ‘714 Patent are drawn to a chemical construct comprising a peptide construct covalently linked to: (a) a targeting ligand; and (b) a first therapeutic oligonucleotide; and, optionally (c) a second therapeutic oligonucleotide that may be the same or different than the first, wherein the amino acid sequence of said peptide construct is selected from the group consisting of: KHHHCKH (SEQ ID NO: 3); HKHHHCKH (SEQ ID NO: 4); HHKHHHCKH (SEQ ID NO: 5); HHHKHHHKCHHHKHHH (SEQ ID NO: 6); HHHKHHCKHHH (SEQ ID NO: 7); HHHKHHCRHHH (SEQ ID NO: 8); HKHHCKH (SEQ ID NO: 9); HKHCH (SEQ ID NO: 10); HKHCKH (SEQ ID NO: 11); HKHC (SEQ ID NO: 12); HHHK(S)HHCKHHH (SEQ ID NO: 13); and HHK(S)HHKCHH(S)HHH (SEQ ID NO: 14), wherein the targeting ligand is linked to the side chain of the cysteine residue and the first oligonucleotide is linked to the side chain of a lysine residue, and wherein (S) is:
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The claims of the present invention are drawn to a chemical construct comprising a Peptide Docking Vehicle (PDoV) covalently linked to (a) a targeting moiety, and (b) a therapeutic nucleic acid, wherein said therapeutic nucleic acid inhibits expression of PCSK9 gene, and wherein the PDoV comprises multiple repeating units of histidine and lysine.
The ‘714 Patent does not teach the therapeutic oligonucleotide inhibits expression of PCSK9 gene.
Alnylam teach siRNA nucleic acids that inhibit the expression of PCSK9 gene as therapeutic nucleic acids.
It would have been obvious and one of skill in the art would have been motivated to modify the teachings of the ‘714 Patent to include a PCSK9 siRNA since the ‘714 Patent taught a peptide docking vehicle for targeted nucleic acid delivery and Alnylam taught the desire to use gene therapy to target PCSK9 gene and protein expression.
The present claims embrace, encompass and overlap in scope with claims 1-12 of the ‘714 Patent in view of Alnylam.
A terminal disclaimer disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12054714 is required, or some other appropriate action.
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