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 .
Election/Restrictions
Applicant’s election without traverse of claims 16-31 and 34 with species election of a fatty acid, octadecanedioic acid, and SEQ ID NO:25 in the reply filed on July 23, 2026 is acknowledged.
Status of Claims
Claims 1-36 are currently pending in the instant application. Claims 1-15, 20, 32-33, and 35-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions/species, there being no allowable generic or linking claim. Accordingly, claims 16-19, 21-31, and 34 are under examination on the merits in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Drawings
The drawings are objected to because Figures 10c and 11 are illegible. Note that the patent application content should be in black font for legibility. Note that application papers must be clearly legible using black colored font text and black lines. See MPEP §608.01.
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.
Specification
The disclosure is objected to for containing sequence rule non-compliant subject matter. See pages 21, 32-33, 39, 41, and 47.
Appropriate correction is required as instructed below.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide sequences appearing in the specification, see pages 21, 32-33, 39, 41, and 47, are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 21-31 and 34 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claims. See MPEP § 608.01(n). Accordingly, claims 21-31 and 34 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.
Claim 19 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 19 recites “preferably, the fatty acid is dodecanedioic acid.” It is unclear whether the limitation following the phrase “preferably” is a required limitation or a mere example thus is not a required feature of the claim.
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.
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 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (WO 2019/154410 A1, applicant’s citation; applicant did not provide a complete English language translation, which is attached herewith) in view of Callmann et al. (JACS, 2019, 141:11765-11769).
Zhang discloses a nucleic acid aptamer binding to and inhibiting sclerostin, wherein the aptamer is 5’-CGGGGTGTGGGTTCGTCGTTAGCTTGATTTGGCAGCTGCC (SEQ ID NO:1; “aptscl56”), which is “specifically tightly bound to osetoscleroprotein” thus is selected for further characterization. See paragraphs 0001, 0008-0011, 0103-0104, and 0110 of the English language translation.
It is noted that Zhang’s SEQ ID NO:1 is 100% identical in sequence with SEQ ID NO:1 claimed in the instant case and differs from SEQ ID NO:25 of the instant application by only one nucleotide at position 37.
Zhang teaches that the aptamer further comprises a modification (e.g., 2’-O-methyl, PEG) that helps “enhance the in vivo half-life” of the aptamer and exemplifies SEQ ID NO:1 being modified with 2’-O-methyl and/or being conjugated with PEG40K-at the 5’ terminus, wherein the 2’-O-methyl-modfiied and the PEG40K-conjugated aptamer “significantly extended the half-life” of the aptamer in serum/blood samples compared to an unmodified/unconjugated aptamer, wherein PEG conjugation “leads to systematic reduction in blood absorption”, thereby providing “rapid decline in the pharmacokinetic curve elimination phase.” See paragraphs 0014, 0118, 0124, 0126, and 0130-0140.
Zhang teaches that “one or more nucleotides, such as 4, are modified at the 5’ and/or 3’ ends of the aptamer, such as 2’-methoxy (2’-OMe) modification.” See paragraph 0053.
Zhang teaches that the aptamer can be “DNA/RNA hybrids”. See paragraph 0038.
Zhang does not teach that the modification that extends the half-life of the aptamer is a fatty acid, especially octadecanedioic acid.
Callmann teaches that “1,18-octadecanedioic acid” (ODDA) that is conjugated to a drug provides binding to human serum albumin (HSA), which is “the most abundant serum protein with myriad functions, including a central role in metabolic pathways as a transporter of long-chain fatty acids (LCFAs) and hydrophobic molecules, both natural and synthetic.” See page 11765.
Callmann reports that ODDA-conjugated drug, “Ozempic (semaglutide)”, has been FDA approved, wherein ODDA contributes to the drug’s performance as a weekly drug. See page 11765.
Callmann reports that ODDA-conjugated paclitaxel, which is bound to HSA provides a higher half-life than a nanoparticle albumin-bound paclitaxel, wherein the ODDA-conjugated drug therefore provides an improved treatment effect. See pages 11766-11768.
It would have been obvious to one of ordinary skill in the art before the effective filing date to replace Zhang’s PEG40K conjugated to the 5’ end of Zhang’s SEQ ID NO:1 with Callmann’s ODDA. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success so as to improve the in vivo pharmacokinetic profile of Zhang’s SEQ ID NO:1 because Zhang’s PEG40K conjugate, albeit useful for improving half-life of the conjugated aptamer, was known to be associated with “systematic reduction in blood absorption”, thereby providing “rapid decline in the pharmacokinetic curve elimination phase”, and because 1,18-octadecanedioic acid (ODDA) was known to bind to “the most abundant serum protein”, human serum albumin (HSA), thus had been successfully utilized in a weekly dose performance of an FDA approved drug, wherein the ODDA conjugation was also known to improve half-life of the conjugated drug as evidenced by the teachings of Callmann. That is, one of ordinary skill in the art would have reasonably deemed that Callmann’s ODDA confers more benefits/advantages compared to Zhang’s PEG40K thus would have reasonably pursued the known drug conjugate option, thereby arriving at the claimed subject matter with a reasonable expectation of success. It would also have been obvious to one of ordinary skill in the art to make an “DNA/RNA hybrid” by incorporating 2’-O-methyl RNA modifications into “4” nucleotides at both the 5’ end (first four positions) and the 3’ end (last four positions) of Zhang’s SEQ ID NO:1 as explicitly taught by Zhang, thereby arriving at the following aptamer sequence, wherein the underlined 4 nucleotides at both the 5’ end and the 3’ end are 2’-O-methyl RNAs.
5’-CGGGGTGTGGGTTCGTCGTTAGCTTGATTTGGCAGCTGCC
That is, it would have been prima facie obvious for one of ordinary skill in the art to readily obtain SEQ ID NO:25 having a 2’-O-methyl modified RNA base at position 37, which would necessarily be a uracil (“U”) in place of the thymine (“T”) in the unmodified DNA form.
In view of the foregoing, claims 16-19 taken as a whole would have been prima facie obvious before the effective filing date.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 16-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,338,441 B2 in view of Zhang et al. (WO 2019/154410 A1, applicant’s citation; applicant did not provide a complete English language translation, which is attached herewith) in view of Callmann et al. (JACS, 2019, 141:11765-11769).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims would have been obvious over the ‘441 patent claims drawn to an aptamer comprising SEQ ID NO:1, further comprising a modification that help “enhance the in vivo half-life of the aptamer” and “comprises a 2’-methoxy (2’-OMe) modification”. It is noted that SEQ ID NO:1 of the ‘441 patent claims is 100% identical to SEQ ID NO:1 claimed in the instant application and also has at least 35 consecutive nucleotides within SEQ ID NO:25 claimed in the instant case. It would have been obvious to incorporate Callmann’s 1,18-octadecanedioic acid (ODDA) as the modification that enhances half-life of the aptamer in view of the properties of ODDA known in the prior art as reported by Callmann as explained in the §103 rejection above, which is fully incorporated by reference herein. It would also have been obvious to one of ordinary skill in the art to readily envision that SEQ ID NO:1 of the ‘441 patent claims comprising 2’-O-methyl RNA modification, especially four bases in both 5’ end and 3’ end regions as taught by Zhang, would have the nucleotide sequence of SEQ ID NO:25 elected by applicant.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM 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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/DANA H SHIN/Primary Examiner, Art Unit 1635
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