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 .
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.
Election/Restrictions
Applicant's election with traverse of “SEQ ID NO. 1” as a species of “RNA polynucleotide” in the reply filed on 16 October 2025, is acknowledged. The traversal is on the ground(s) that Examiner allegedly pointed to a Table 17 and indicate that it disclosed potential species of “RNA polynucleotide”. However, Applicants indicate it contains exemplary IRES embodiments.
Furthermore, Applicant’s election without traverse of “
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” as a species of “genus formula 6” in the reply filed on 16 October 2025, is acknowledged.
Examiner acknowledges Applicants’ election with traverse for “RNA polynucleotide” as summarized, above, and the election without traverse of species of genus formula 6. However, Examiner has withdrawn the Election of Species Requirement as independent claims 253 and 270 are free of the prior art (see, below). Thus, the traversal and Examiner response thereto are rendered moot.
Applicants’ compliant species election of SEQ ID NO 1 as species of “RNA polynucleotide” and
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as species of “genus formula 6”, wherein “n” is 0 or 8; L1 and L3 are each -C(O)O-* and “*” indicates attachment point to R1 or R3; R1 and R2 are each branched C12alkyl; R3 is
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; and R4 is linear C9alkyl, retrieved no prior art references.
The Examiner’s extended Markush search to the full scope of genus formula 6 from instant claim 253 and full scope of genus formula 1 from instant claim 270 did not retrieve any prior art.
Therefore, the Election of Species Requirement of 16 July 2025, is withdrawn, as all claims are free of the prior art.
All claims have been examined on the merits.
Current Status of 17/998,219
This Office Action is responsive to the amended claims of 16 October 2025.
Claims 253-275 have been examined on the merits. Claims 253-260 and 262-272 are previously presented. Claim 261 is currently amended. Claims 273-275 are new.
Priority
The effective filing date is 8 May 2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3 June 2024; and 9 June 2023, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 259 is objected to because Applicants refer to “the RNA” and not -- the RNA polynucleotide -- as is required by instant claim 253. Examiner understands that “RNA” of claim 259 refers to “RNA polynucleotide” of claim 253 since that is the only RNA of the pharmaceutical composition of claim 253 and 259. However, to be technically correct, please add -- polynucleotide -- as directed, above.
Claim 260 is similarly objected to as this claim refers back to claim 259 but does not remedy the rationale underpinning the basis for objecting to claim 259.
Claim Rejections - 35 USC § 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 269 and 272 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating leukemia with the pharmaceutical compositions of claims 253 and 270, does not reasonably provide enablement for treating or preventing the undefined/unlimited scope of diseases of claims 269 and 272. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The Wands Factors used in an (scope of) enablement rejection include (per MPEP 2164.01(a)):
The breadth of the claims:
The only two method claims (claims 269 and 272) are each drawn to a method of treating or preventing any disease (since claims 269 and 272 do not define the scope of diseases to be treated and/or prevented) by administering the pharmaceutical compositions of claims 253 and/or 270.
The nature of the invention:
The invention belongs to biotechnology, more specifically, gene therapy involving pharmaceutical compositions comprising: RNA polynucleotides and Applicants’ own compounds of either genus formula 6 (claim 253) or formula 1 (claim 270). The invention also entails administering said pharmaceutical compositions to treat or prevent an unspecified scope of diseases or disorders (per claims 269 and 272). As stated, above, the Examiner is interpreting the broadest reasonable interpretation (BRI) of method claims 269 and 272 to include treating or preventing any disease (since Applicants have not narrowed the scope of claims 269 and 272 to a list of specific diseases) with the pharmaceutical compositions of claims 253 and/or 270.
The state of the prior art:
A review of STN’s Registry, HCaplus, and Casreact databases does not find prior art for genus formula 6 and genus formula 1 of claims 253 and 270, respectively. Similarly, a review of Global Dossier, the numerous cited references incorporated by reference in Applicants’ Specification, the references cited by the Written Opinions and International Search Reports for: both PCT/US2021/031629 and PCT/US2020/063494; and the references cited within Applicants’ provided Information Disclosure Statements (IDS) do not find prior art for genus formula 6 (claim 253) or genus formula 1 (claim 270).
Furthermore, there is no known prior art that would support treating or preventing the unlimited scope of diseases or disorders per the BRI (see, above) of instant claims 269 and 272.
Moreover, reference MEDICINE (UT Southwestern Medical Center. “Leukemia Awareness and Prevention.” Published: 11 March 2018. Accessed 16 February 2026. Available from: < https://utswmed.org/conditions-treatments/leukemia/leukemia-awareness-and-prevention/ >), proves that leukemia cannot be prevented (see page 3 of 4).
The level of one of ordinary skill:
The level of one of ordinary skill includes the knowledge/skill to engage in a reasonable amount of experimentation to make and use the pharmaceutical compositions of claims 253 and 270 based on the disclosure in the Specification (Example 1 page 589-Example 36 page 626 of the instant Specification).
The one of ordinary skill also has the knowledge to engage in a reasonable amount of experimentation to treat some diseases, such as leukemia. However, no one has skill to engage in the undue burdensome level of experimentation required to provide guidance/enablement for treating or preventing the unlimited/undefined scope of diseases/disorders of the claims 269 and 272.
The level of predictability in the art:
The art is predictable to make the instantly claimed pharmaceutical compositions. However, the art does not provide predictability as to which diseases and disorders can be treated or prevented. To generate this level of guidance, one has to engage in undue burdensome experimentation (since no predictability in the art) to test the pharmaceutical composition against every disease known to humanity to determine if the pharmaceutical composition can treat and/or prevent said disease(s). This level of experimentation would be required to match the scope of instant claims 269 and 272.
The amount of direction provided by the inventor:
Inventors have provided direction as to making the pharmaceutical composition (Example 1 page 589-Example 36 page 626 of the instant Specification). Inventors have also provided direction as to using the pharmaceutical composition to treat (but not prevent) leukemia (see Example 67 page 662 of the instant Specification).
The existence of working examples; and
Applicants’ Specification provides guidance/enablement with working examples of how Applicants synthesized their compounds of genus formula 6 (claim 253) and genus formula 1 (claim 270). See, for example, Example 36 (pages 626-642 of the instant Specification).
The instant Specification also includes enablement/guidance with working examples for constructing the RNA polynucleotides (see Example 1 page 589-Example 35 page 626 of the instant Specification).
The only working example of a disease that Applicants used the instantly claimed pharmaceutical composition (comprising RNA polynucleotide and genus formulae 6 or 1) to treat are leukemia cell lines (K562 cells) (see Example 67 page 662 of the instant Specification).
Thus, Applicants have guidance/enablement in their Specification Example 67 for treating leukemia by administering the instant pharmaceutical compositions of claims 253 and 270. This guidance does not support preventing leukemia.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
Applicants’ gene therapy invention comprising RNA polynucleotides require a high level/quantity of experimentation to make/use the invention. While Applicants have provided guidance in their Specification for making the pharmaceutical composition of claims 253 and 270, they have not provided enough evidence that said pharmaceutical composition can be used to treat or prevent the unlimited / undefined scope of diseases or disorders per the BRI of instant claims 269 and 272. At best, the Specification does provide enablement/guidance for using the instantly claimed pharmaceutical composition to treat (not prevent) leukemia (see Specification Example 67 page 662).
Therefore, claims 269 and 272 are both rejected under 35 USC 112(a) for lacking scope of enablement for the scope of treating or preventing an undefined number (unlimited number) of diseases or disorders.
To render moot this scope of enablement rejection: Applicants should delete “prevent” and/or “prevention”/”preventing” from the claims.
Furthermore, Applicants should disclose the scope of diseases or disorders in each of claims 269 and 272 for which Applicants believe their specification provides guidance/enablement. Please point to specific Examples by example number and page number and explain how those example(s) demonstrate the guidance/enablement needed.
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 253-269 and 273-275 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 253 recites the limitation "wherein “*” indicates the attachment point to R1 or R3". There is insufficient antecedent basis for this limitation in the claim.
As drafted, the limitation "wherein “*” indicates the attachment point to R1 or R3" lacks antecedent basis with the bonding relationships/associations as illustrated in the illustration of genus formula 6 in line 4 of the claim 253. In that illustration, L3 attaches to R2 but the limitation in the claim narrative which lacks antecedent basis says “wherein “*” indicates the attachment point [of L3] to R3”. This renders the metes and bounds of claim 253 undefined (hence rendering claim 253 indefinite under 35 USC 112(b)).
Don’t Applicants really intend L3 to attach to R2 as per the illustration? Thus, arises the lack of antecedent basis, since the narrative does not match the illustration, per explanation, above.
Claims 254-269 and 273-275 are similarly rejected as indefinite under 35 USC 112(b) since these claims refer back to claim 253 but do not remedy the rationale underpinning the basis for rejecting claim 253.
Revising the claim 253 narrative to accurately reflect L3 bonding to R2 should remedy this rejection.
Claim 265 contains “includes” (see embodiment b on page 9), which renders the metes and bounds of the claim undefined (hence rendering claim 265 indefinite under 35 USC 112(b)). The artisan does not know whether the limitations following “modified nucleoside includes” are merely exemplary or are required limitations of the claim.
Please delete “include” to render moot this rejection.
Claim 259 recites the limitation "the RNA". There is insufficient antecedent basis for this limitation in the claim.
As drafted, “the RNA” of claim 259 renders the metes and bounds of claim 259 undefined (hence rendering claim 259 indefinite under 35 USC 112(b)) as the artisan does not know where antecedent basis is for “the RNA”. Could Applicants really intend -- the RNA polynucleotide -- ? Parent claim 253 does not contain “a RNA”; rather, parent claim 253 contains “a RNA polynucleotide”.
Claim 260 is similarly rejected as indefinite since it refers back to claim 259 but does not remedy the rationale underpinning the basis for rejecting claim 259.
Adding “polynucleotide” in claim 259 as in: -- the RNA polynucleotide -- should remedy this rejection.
The term “substantially free” in claim 268 is a relative term which renders the claim indefinite. The term “substantially free” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such, “substantially free” of claim 268 renders the metes and bounds of claim 268 undefined (hence rendering claim 268 indefinite under 35 USC 112(b)) since the artisan is not certain by what standard to measure “substantially free” since “substantial” and/or “substantially” and/or “substantially free” are not defined in the claims or Specification.
Please strike “substantially” from the claim to render moot this rejection.
Claim 253 contains the embodiment “C1-C15 alkenyl” for variable R4. This renders the metes and bounds of claim 253 undefined (hence rendering claim 253 indefinite under 35 USC 112(b)) since the artisan is not certain how a C1alkenyl can exist. An “alkenyl” requires at least one carbon-carbon double bond, wherein the double bond is between two carbon atoms (-C=C-). Hence, the smallest number of carbon atoms in an “alkenyl” is C2. Therefore, please revise to -- C2[[C1]]-C15alkenyl -- for R4 to render moot this rejection.
Claims 254-269 and 273-275 are similarly rejected as indefinite under 35 USC 112(b) since these claims refer back to claim 253 but do not remedy the rationale underpinning the basis for rejecting claim 253.
New claims 273-275 recites various IRES embodiments from claim 261 that Applicants deleted from claim 261. There is insufficient antecedent basis for this limitation in the claims 273-275.
As drafted, the limitations of claims 273-275 render the metes and bounds of these claims undefined (hence rendering claims 273-275 indefinite under 35 USC 112(b)) since the artisan has no idea where the limitations from each of claims 273-275 are found in parent claim 261, as Applicants deleted the embodiments now seen in new claims 273-275 from claim 261.
Canceling claims 273-275 will render moot this rejection.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 259 and 273-275 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Dependent claim 259 contains the limitation “the RNA”. However, this does not permit dependent claim 259 to properly further limit parent claim 253, since claim 253 contains “the RNA polynucleotide”. Therefore, claim 259 is rejected under 35 USC 112(d). Applicants should revise claim 259 to: -- the RNA polynucleotide -- to remedy this rejection.
Claim 260 is similarly rejected under 35 USC 112(d) since it refers back to claim 259 but does not remedy the rationale underpinning the basis for rejecting claim 259.
New dependent claims 273-275 improperly further limit claim 261: claims 273-275 contain embodiments that Applicants deleted from claim 261. Hence, the embodiments now seen in claims 273-275 do not further limit the revised claim 261. Thus, claims 273-275 are rejected under 35 USC 112(d).
Canceling claims 273-275 will render moot this rejection.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
Claims 253-269 and 272-275 are not presently allowable as written.
Claims 270-271 are presently allowable as written.
There is no known prior art reference that either teaches or anticipates the genus formula 6 (a required limitation of independent claim 253) and/or the genus formula (1) (a required limitation of independent claim 270). Hence, independent claims 253 and 270 are both free of the prior art.
The reference WESSELHOEFT (Wesselhoeft, R. Alexander, et al. “RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo.” Molecular Cell. (May 2, 2019), 74(3), pp. 508-520, provided by Applicants-and referenced in IDS of 9 June 2023), discloses circular RNA (see page 508).
However, WESSELHOEFT is a close art but not a prior art reference as it is silent as to genus formula 6 of independent claim 253 and/or genus formula 1 of independent claim 270.
Furthermore, Examiner reviewed the instant Specification; the Written Opinions and International Search Reports for: both PCT/US2021/031629 and PCT/US2020/063494; the Applicant-provided Information Disclosure Statements (IDS); the Global Dossier; and the Examiner-conducted STN search for genus formula 6 and genus formula 1, but did not find any prior art or double patent art reference for/against genus formulae 6 or 1. In fact, genus formula 6 and genus formula 1 do not retrieve any hits within Registry, HCaplus, or Casreact databases of STN.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN S KENYON whose telephone number is (571)270-1567. The examiner can normally be reached Monday-Friday 10a-6p.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew D Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625