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 4 June 2026. Claims 122-130, 133-134, 136-148, and 151 are currently pending. Claims 125-126 and 148 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 122-124, 127-130, 133-134, 136-147, and 151 are examined herein. The restriction requirement mailed 6 January 2025 is still deemed proper. Applicant's elected Group I alongside the species of an mRNA, SEQ ID NO: 3, an extension rate of at least 150 nucleotides per minute, and an error rate of less than 1:1000 without traverse in the reply filed 25 February 2025.
Any rejection or objection not reiterated herein has been overcome by amendment.
Applicant' s amendments have been thoroughly reviewed, but are not persuasive to place the
claims in condition for allowance for the reasons that follow.
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 that is 40-200 nucleotides in length and comprises 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 that is 40-200 nucleotides in length and comprises 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 that is 40-200 nucleotides in length and comprises the claimed SEQ ID NO: 3. While claiming a genus of structures (i.e., DNA templates that are 40-200 nucleotides in length and comprise 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, with lengths of 78 nucleotides, 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]) not utilized in the DNA templates in the working examples, which instead only 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 that are 40-200 nucleotides in length and comprise claimed SEQ ID NO: 3 while the specification does not teach the use of a DNA template that is 40-200 nucleotides in length and comprises 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 are 40-200 nucleotides in length and 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 an 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).
Response to Arguments
Applicant's arguments filed 4 June 2026 have been fully considered but they are not persuasive.
Applicant alleges that the combination of structural and functional features of the DNA template of the present claims is sufficient to support the written description requirement (pg. 6). Applicant alleges that because the presently amended claims require a combination of structural and functional features of DNA templates described in the specification such that one of skill in the art could recognize the members of the genus, and thus appreciate that the applicant was in possession of the claimed invention, the presently amended claims satisfy the written description requirement due to the disclosures in the specification (Remarks; pg. 7). Applicant alleges that because MPEP 2163 does not explicitly require a working example in order to show possession of the claimed invention, the disclosure present in the instant specification is sufficient to show possession of the claimed DNA template having the claimed function Remarks; pg. 8).
These arguments are not found persuasive because MPEP 2163 further teaches that “[a]n invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function.” In the instant case, the claimed method is defined by providing the claimed DNA template that is 40-200 nucleotides in length and comprises the claimed SEQ ID NO: 3 and that same DNA template having the function of being able to synthesize a plurality of RNAs at an extension rate of about at least 50 nucleotides per minute (see Claim 151). Accordingly, the claimed structure of the DNA template is defined by its claimed function. The instant specification has not described a correlation between the structure of the claimed DNA template that is 40-200 nucleotides in length and comprises SEQ ID NO: 3 and the claimed function of being able to support the claimed extension rate.
As discussed above in the maintained 35 USC 112(a) rejection of record, a thorough review of the prior art demonstrates that the extension of RNA molecules from different DNA templates is unpredictable and is dependent on many different factors stemming from the interaction that RNAP has with a particular RNA molecule. Additionally, the working examples provide evidence that utilizing the claimed wildtype RNA polymerase promoter does not result in the claimed extension rate and it is unpredictable that the claimed structure could achieve the claimed extension rate.
The working examples of the non-truncated, wildtype, T7 RNA polymerase promoters did not demonstrate any fold improvement over the truncated promoters nor demonstrated evidence of being able to achieve a rate of extension of at least 50 nucleotides per minute ([0031]-[0032]; see Figure 17A-B). Figure 17A charts a real time measurement of ribonucleotide transcriptional output wherein the X-axis shows time and the Y-axis shows fluorescent readings in RFU ([0031]). Figure 17A demonstrates that the starting point and at one hour, the RFU value of the traditional promoter was around 1500 RFU and did not increase to the degree that the truncated promoters did, and instead appeared to decrease over time (i.e., the RFU value did not increase at a rate of 50 RFU/min and therefore the rate of extension was not 50 nucleotides per minute) (see Figure 17A). Thus, the working examples provide evidence that the use of the claimed SEQ ID NO: 3 (i.e., the wildtype T7 RNA polymerase promoter) does not predictably result in an extension rate of at least 50 nucleotides per minute. Thus, a person of ordinary skill in the art would interpret the ability of the claimed structure to perform the claimed extension rate as being unpredictable and that achieving the claimed rate of extension with the claimed structure is not expected.
Accordingly, a person of ordinary skill in the art would not recognize that Applicant has possession of the structure of DNA templates that are able to perform the claimed function as recited in the claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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 Mon-Fri, 9AM-5PM (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
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