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 .
Application Status
This action is written in response to applicant’s correspondence received 13 November 2025. Claims 121-130, 133-134, 136-148, and 151 are pending. Claims 121-130, 133-134, and 136-146 are amended. Claims 125-126 and 148 are withdrawn. Accordingly, claims 122-124, 127-130, 133-134, 136-147, and 151 are currently under examination.
Withdrawn Claim Rejections
Applicant’s amendment, filed 13 November 2025, has been fully considered and are deemed persuasive. Accordingly, the previous 35 USC 112(a) enablement and 35 USC 103 rejections of claims 121-124, 127-134, 136-147, and 149-150 35 USC § 103 have been withdrawn. However, upon further consideration, the claims remain unpatentable for reasons outlined below that were not necessitated by amendment. Therefore, this action is NON-FINAL.
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 122-124, 127-130, 133-134, 136-147, and 151 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.
Regarding claim 151, the claim is broadly drawn towards an in vitro method of synthesizing RNAs, comprising providing a T7 RNA polymerase and a DNA template comprising the claimed SEQ ID NO: 3, wherein the synthesis of RNAs is performed at an extension rate of at least 50 nucleotides per minute.
Accordingly, the claims are interpreted as claiming a method of synthesizing RNAs at a predetermined rate via the use of a DNA template comprising the claimed SEQ ID NO: 3. The instant specification does not provide support for the use of a DNA template comprising the claimed SEQ ID NO:3 such that an RNA molecule is synthesized at a rate of at least 50 nucleotides per minute and the prior art provides evidence that the use of the claimed SEQ ID NO: 3 was not known and that rates of extension of RNA molecules is unpredictable.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include "level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would leave one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP 2163. A claimed genus may be satisfied through sufficient descriptions of a representative number of species or disclosure of relevant, identifying characteristics such as functional characteristics coupled with known or disclosed correlation between function and structure. MPEP 2163(3)a(II). The number of species that describe the genus must be adequate to describe the entire genus; if there is substantial variability, a large number of species must be described.
The analysis for adequate written description considers (a) actual reduction to practice, (b) disclosure of drawings or structural chemical formulas, (c) sufficient relevant identifying characteristics in the way of complete/partial structure or physical and/or chemical properties or functional characteristics when coupled with known or disclosed correlation with structure, and (d) representative number of samples.
As the claims currently recite, as described above, the claim is directed towards a method of synthesizing RNAs at a predetermined rate (i.e., a rate of extension of at least 50 nucleotides per minute) via the use of a DNA template comprising the claimed SEQ ID NO: 3. While claiming a genus of structures (i.e., DNA templates comprising the claimed SEQ ID NO; 3) by a function (i.e., the claimed rate of extension) is not prohibited, there must be a sufficient structure-function relationship described in the specification such that the claimed genus was represented by a representative number of species or the teachings of the specification, or, the prior art can be used to support a well-known structure-function relationship.
In the instant case, the instant specification does not provide support that the broadly claimed DNA templates that are able to perform the claimed function. Further, the prior art demonstrates that the use of the claimed SEQ ID NO: 3 was not known and that rates of extension of RNA molecules from different DNA templates is unpredictable.
Working Examples
With regard to working examples, the specification provides little evidence on the possession of a sufficient number of species which are encompassed by the entirety of the claimed genus.
MPEP 2163 teaches that “for some arts, there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed [emphasis added].”
In the instant case, the specification teaches the use of a set of 6 DNA templates that were able to be utilized to synthesize RNA molecules at an extension rate of at least 50 nucleotides per minute (pg. 57; see FIGs. 17A-17B). The specification teaches that truncated promoters with enzyme binding domains were able to achieve the claimed nucleotide extension rate (pg. 57; see FIGs. 17A-17B). However, the claimed SEQ ID NO: 3 is directed towards a wildtype T7 RNA polymerase promoter sequence ([0148]) while the DNA templates in the working examples do comprise the claimed SEQ ID NO: 3 and instead comprise truncated T7 RNA polymerase promoters (pg. 57; see Table 2).
Thus, when taken as a whole, the set of DNA templates present in the specification is not representative of the claimed genus as a whole because the claimed genus broadly encompasses a method that can performed the claimed function only through the use of DNA templates comprising the claimed SEQ ID NO: 3 while the specification does not teach the use of a DNA template comprising the claimed SEQ ID NO: 3 that can perform the claimed function. Therefore, the instantly claimed genes of DNA templates present in claim 151 is not adequately described in the specification as being able to facilitate an extension rate of at least 50 nucleotides per minute.
Thus, the instant specification does not provide written description for the entirety of the claimed method comprising DNA templates that comprise the claimed SEQ ID NO: 3 (see Claim 151).
Prior Art
Regarding the state of the prior art, the prior art demonstrates that the claimed SEQ ID NO: 3 was not known and that rates of extension of RNA molecules from different DNA templates is unpredictable
Belitsky (Journal of theoretical biology 462 (2019): 370-380) is directed towards a study concerned with RNA polymerase (i.e., RNAP) elongation rates (Abstract). Belitsky teaches that the major and generic features of the multi-step mechano-chemical pathway of individual RNAP motors during each elongation step are: (1) Nucleoside triphosphate (NTP) binding at a catalytic site within the transcription bubble, (2) NTP hydrolysis, (3) Release of pyrophosphate (PPi, one of the products of hydrolysis), and (4) Forward step of the RNAP along the DNA template by one base pair (bp) (pg. 370). Belitsky teaches that elongation rate of RNA mediated by RNA polymerases is variable and depends on many factors including NTP concentration in the DNA template (pg. 375; see Fig. 2).
Thus, the prior art shows that prior to the effective filing date of the claimed invention it was not predictable that a broad set of DNA templates comprising the claimed SEQ ID NO: 3 could be utilized in a method of RNA synthesis as claimed. Rather, the prior art shows that the rate of RNA extension mediated by an RNAP is variable and depends on many factors including how the RNAP interacts with the DNA template. Further, the prior art provides evidence that a large amount of experimentation was required in order to determine a RNA extension rates mediated by an RNAP from a DNA template.
Conclusion
The specification does not identify a representative number of species of the broadly claimed set of DNA templates genes that possess the claimed function of mediating an extension rate of at least 50 nucleotides per minute. Further, the prior art shows that prior to the effective filing date of the claimed invention that determining the rate of extension of an RNA molecule from a DNA template was unpredictable and highly specific to the DNA template.
Therefore, a person of ordinary skill in the art would not have concluded that Applicant was in possession of the invention as claimed. Thus, claim 151 is rejected under 35 U.S.C. 112(a).
Regarding claims 122-124, 127-130, 133-134, and 136-147, as the claims are ultimately dependent on claim 151 and do not rectify the 35 USC 112(a) rejection above, the claims are also rejected under 35 USC 112(a).
Claim 136 is 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 utilizing avidin as a nucleic acid binding protein that can bind to a biotinylated DNA template (instant specification; [0177]), does not reasonably provide enablement for utilizing avidin alone as a nucleic acid binding protein that can bind to any DNA template for RNA synthesis. 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.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex part Forman. They include (1 the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of these in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
Regarding claim 136, the claim recites that the nucleic acid binding protein is an avidin comprising streptavidin, rhizavidin, or neutravidin.
The state of the art, the unpredictability of the art, and the relative skill of the ordinary artisan
It is well established in the art that avidin can be utilized to bind to biotinylated nucleic acid molecules. Carlson-Stevermer (Nature communications 8.1 (2017): 1711) is drawn to a study concerned with the assembly of CRISPR ribonucleoproteins with biotinylated oligonucleotides via an RNA aptamer (Title; Abstract). Carlson-Stevermer teaches the use of a complex comprising a Cas9, a Cas9 sgRNA comprising an RNA aptamer that has a strong non-covalent interaction with streptavidin, and a biotinylated single-stranded oligodeoxynucleotide donor templates (i.e., biotinylated nucleic acid molecules) (pg. 2; see Fig. 1). Carlson-Stevermer teaches that it is well known in the art that streptavidin has a strong interaction with biotin (pg. 5). Carlson-Stevermer teaches that the streptavidin-biotin interaction was able to successfully recruit the complex to the biotinylated single-stranded oligodeoxynucleotide donor templates (pg. 2; see Fig. 1).
Further, Lesch (Expert opinion on drug delivery 7.5 (2010): 551-564) is drawn towards a review study concerned with avidin-biotin technology in targeted therapies (Abstract). Lesch teaches that it was well known in the art that avidin’s and streptavidin’s “main biological function is to bind biotin” (pg. 552). Lesch teaches that the binding affinity of avidin and biotin has been utilized across a wide variety of applications, including targeting cancer cells for therapy (pg. 555), targeting therapeutics to target cell surfaces (pg. 557), and targeting vectors to specific viral and cell membrane epitopes (pg. 556-557).
However, utilizing avidin alone as a nucleic acid binding protein that can bind to any DNA template, including non-biotinylated DNA templates, as presently claimed, is unpredictable because the prior art does not teach that avidin alone can be utilized to bind to any nucleic acid molecule. In addition, the skill of those in the relative art is high, but still, given the state and unpredictability of the art, undue experimentation would be required to determine if avidin alone could be utilized as presently claimed to synthesize RNA in vitro. Utilizing avidin to bind to non-biotinylated DNA cannot be predictably accomplished, much less alongside a T7 RNA polymerase in order to synthesize a plurality of RNAs based on the sequence of at least part of the DNA template, as presently claimed.
Amount of experimentation required and the direction or guidance presented
In order to determine how to act, one of ordinary skill in the art would have to practice undue experimentation to determine if RNA may be synthesized in vitro by utilizing an avidin as a nucleic acid binding protein alongside DNA templates that do not comprise biotin. Even if the method was performed as claimed, there is no evidence in the prior art nor the instant specification that avidin alone could be utilized to recruit a T7 RNA polymerase to any DNA template in order to synthesize RNA based on the DNA template, as claimed. The mere ability to administer a T7 RNA polymerase linked to an avidin to a DNA template of interest is not representative of the ability to predictably use the invention as claimed. In addition, the specification, as filed, fails to provide any particular direction or guidance which resolves the known unpredictability in the art associated with avidin binding to a DNA template without the presence of biotin in the DNA template.
Nature of the invention, the presence or absence of working examples, and the breadth of the claims
While the specification does provide support for utilizing avidin as a nucleic acid binding protein that can bind to a biotinylated DNA template ([0177]), it fails to disclose how to utilize avidin alone to bind to any DNA template, as encompassed by the claims. Because the claimed invention claims that the nucleic acid binding protein is avidin and the DNA template is not required to be biotinylated, the specification does not provide any disclosure to enable the claims over their full scope. Therefore, the claim is not enabled commensurate in scope with the claimed invention.
Response to Arguments
Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons above.
Closest Prior Art
Regarding claim 151, the closest prior art is Tuttle (US Patent No. 9,909,132 B2). Tuttle is drawn to an invention concerned with application to a host plant to reduce, inhibit or impair one or more of growth and development of the host plant (Abstract). Tuttle teaches the use of a synthetic sequence comprising a T7 RNA Polymerase promoter having 83% sequence identity to the claimed SEQ ID NO: 3 (Col. 26; see SEQ ID NO: 20 in previously attached sequence alignment).
However, neither Tuttle nor the prior art renders obvious the needed modifications required in order to arrive at a T7 RNA polymerase promoter comprising the instantly claimed SEQ ID NO: 3 (see Claim 151).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636