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 .
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
The Office contacted the applicant’s representative on 5/19/26 to discuss the remaining issues and left a voicemail. On 5/22/26, an associate for the representative left a voicemail with the Office that the applicant’s representative was out of town and would return the week of the 25th. Unfortunately, the Office had to mail an office action for the instant application and did not have time to wait for applicant’s representative to call the Office to discuss the 112a rejection. After applicant’s representative has had time to review the instant office action, they can call the Office to set up a time and date to discuss the rejection.
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 1-3, 5-7 and 9-20 remain 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.
The claimed invention embraces a genetically modified bacteria engineered to co-express a heterologous bacterial RNase III mutant and a heterologous target dsRNA molecule, wherein the mutant is derived from a wild type RNase III from a bacteria selected from the group consisting of: E. coli, Enterobacter sp., and Bacillus sp., wherein the heterologous bacterial RNase III mutant is a triple or quadruple mutant set for in instant claim 1. Original claim 8 (now cancelled) listed the bacteria set forth in amended claim 1. Pages 51-52 of the specification provide a definition for the term "RNase III". The claimed invention embraces a wild type RNase III from E. coli, Enterobacter sp., and Bacillus sp. having a triple or quadruple mutant comprising at least one of the following: residues 38, 65, 107 and 108 RNase III mutants and upon expression cleaves target dsRNA molecules into sRNA molecules of discrete size capable of inducing RNA silencing in a target pathogen. The amino acid sequence from each claimed species for the specific mutants may vary between RNase III enzymes from different sources. For example, E38 in E. coli corresponds to E37 in Aquifex aeolicus. Paragraph 410 discloses that the inventors demonstrated the construction of Bacillus cereus 53522 E58A mutant. The specification does not appear to disclose that a Bacillus sp. having a triple or quadruple mutant comprising at least one of the following: residues 38, 65, 107 and 108 RNase III mutants and upon expression cleaves target dsRNA molecules into sRNA molecules of discrete size capable of inducing RNA silencing in a target pathogen. The specification has written support for E. coli and Enterobacter sp. having the desired biological property or activity, since they appear to have a conserved sequence with this specific mutants. A search of the prior art does not disclose that Bacillus sp. listed in the claim would have the same RNase III mutants, E38A, E65A, R107A, and/or R108A. The claims require the mutation at these specific sites of an amino acid sequence of the bacteria listed in the claims. Thus, if a skilled artisan made these mutations at the same amino acid residues of E. coli or Enterobacter in Bacillus it might not result in the desired biological activity. Since amino acid positions may vary between RNase III enzymes from the species of bacteria recited in the instant claims (pages 51-52 of the specification). A skilled artisan would understand that a modification of at least one amino acid in a sequence of a Bacillus sp. might change the activity of the RNase III. The description of E. coli and Enterbacter does not represent the other species listed in claim 1. In addition, in view of the variability between RNase III mutants, E. coli and Enterobacter sp do not adequately describe and represent the different species of bacteria listed in claim 1. It would require further experimentation (not undue) to determine if the residues of mutations are actually in Bacillus sp. and would result in the desired biological activity. It is acknowledged that identifying homologs mutants is well within the scope of a skilled artisan and there are several widely-available (and commonly used) tools and databases that can be used to find homologous protein sequences and identify their conserved regions. However, this does not provide written support for instant claim 1 and claims dependent therefrom because adequate written description of RNase mutants set forth instant claim 1 is not based on tools that are routine and conventional in the prior art to determine which amino acids, but that neither the specification nor the prior art of record disclose that specific RNase III mutants are found in B. subtilis. See Amgen V. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) in MPEP 2163. For the reasons set forth above, the limited description in the specification does not provide written support for RNase III mutants from Bacillus sp. having the desired biological activity.
In view of the foregoing, it is clear that the specification of the instant disclosure fails to convey to the skilled artisan that the applicant had possession of the claimed genus of RNase III mutants derived a bacteria selected from the group set forth in instant claim 1 and claims dependent therefrom.
Response to Arguments
Applicant's arguments filed 4/7/26 have been fully considered but they are not persuasive.
In response to applicant’s argument that in view of the amendment to the instant claims limiting the scope to three species of bacteria (E. coli, Enterbacter, and Bacillus), the original disclosure, including the working examples and descriptive guidance clearly conveys that the inventors invented and possessed, as of the filing date, RNase III mutants from these three species, as well as homologous RNase III mutants thereof having the specified mutations, the argument is not found persuasive because as stated in the written description, the instant disclosure only has written support for E. coli sp. and Enterobacter sp. having the desired biological activity. Absence evidence to the contrary, the specification does not appear to disclose that a Bacillus sp. has a E at positions 38 or 56 or R at positions 107 and 108. Also, there is no Bacillus sp. described in the specification or the prior art having the claimed RNase III mutants having the desired biological activity (upon expression cleaved target dsRNA molecule into sRNA molecules of a discrete size capable of inducing RNA silencing in a target pathogen).
Applicant argues that unlike recent biotechnology cases-including Amgen v. Sanofi cited in the office action, the present claims do not define the genus solely by functional language, rather the claims define the homologous RNase III mutants by what they are, not merely what they do (see also Ariad Pharmaceutical, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010)).
Applicant’s arguments is not found persuasive because as stated in the written description, the instant disclosure only has written support for E. coli sp. and Enterobacter sp. having the desired biological activity. There appears to be no Bacillus sp. described in the specification or the prior art having the claimed RNase III mutants and desired biological activity.
Applicant further argues that the claims do not purport to encompass any homologous protein merely having the recited function as suggested by the office action, instead the claims narrowly require homologous RNase III mutants having conserved residues at positions homologous to the specified residues, with each such conserved residue replaced by alanine, the argument is not found persuasive because as stated in the written description, the instant disclosure only has written support for E. coli sp. and Enterobacter sp. having the desired biological activity. There appears to be no Bacillus sp. described in the specification or the prior art having the claimed RNase III mutants having the desired biological activity.
In response to applicant’s argument that based on the detailed claim language, the disclosure, and the general knowledge of those skilled in the art, a skilled artisan would readily envision such homologous RNase III mutants using routine and conventional tools and would recognize that applicant was in possession of the claimed subject matter as of the filing date, the argument is not found persuasive because the rejection is not based on whether or not one of skill in the art can envision homologous RNase III mutants, but the apparent issue that there is no Bacillus sp. described in the specification or the prior art having the claimed RNase III mutants having the desired biological activity. In addition, using routine and conventional tools to make the claimed genetically engineered modified bacteria does not provide written support for the claimed product. Methods for making a product based on routine conventional methods do not provide written support for the product. See Amgen V. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) in MPEP 2163.
Applicant also argues that the Examiner acknowledged that any testing required to confirm biological activity would not be undue or extensive, effectively conceding that the claims are enabled. See also Ajinomoto Co. v. Int’l Trade Comm’n 932, F. 3d 1342 (Fed. Cir. 2019). The Office raises the uncertainty regarding whether the conserved residues are present or functionally equivalent in other species, such concerns sound in enablement-not written description- and should not be conflated with possession inquiry.
Applicant’s arguments are not found persuasive because as stated in the written description, the instant disclosure only has written support for E. coli sp. and Enterobacter sp. having the desired biological activity. There appears to be nothing of record to describe that Bacillus sp. having the claimed RNase III mutants would possess the desired biological activity. The rejection is under written description because while one of skill in the art can make a Bacillus sp. have these mutations, in view of lack of written description in the instant disclosure or prior art, the skilled artisan would have to further experiment with the engineered bacteria to determine if possess the desired biological property. This would indicate that the applicant does not have written support for the claimed product.
In response to applicant’s argument that the office action is incorrect in asserting that identifying homologous residues is not routine and conventional (See also Boston Sci. Corp. v. Johnson & Johnson, 647 F. 3d 1353, 1366 (Fed. Cir. 2011)), the argument is not found persuasive because the office action acknowledged that one of skill in the art can identify homolog mutants but there is no Bacillus sp. described in the specification or the prior art having the claimed RNase III mutants and desired biological activity. In addition, while one of skill in the art can identify homologous residues, they would have to further experiment with each Bacillus sp. to determine if it has the desired biological activity (RNase III) because this specific mutations do not appear to be found in Bacillus sp.
The Declaration under 37 CFR 1.132 filed 4/7/26 is insufficient to overcome the rejection of claims 1-3, 5-7, and 9-20 based upon 112a rejection as set forth in the last Office action because: the Declaration is not found persuasive because the declaration does not appear to disclose that Bacillus sp. having the claimed RNase III mutants would the desired biological activity. Figure 3 of WO 2005072272 appears to disclose the Bacillus subtilis does not have a glutamic acid at position 38, but a phenylalanine at position 38. The declaration does not disclose that an amino acid sequence for any Bacillus sp. has an E at position 38 and/or 65 and/or an R at positions 107 and/or 108. Furthermore, the declaration does not disclose that having the any Bacillus having the claimed triple or quadruple mutant comprising at least one of the following: residues 38, 65, 107 and 108 would still retain biological activity of RNase III. The declaration appears to address issues that are not the basis for the written description rejection. As stated in the written description rejection of record, the instant disclosure only has written support for E. coli sp. and Enterobacter sp. having the desired mutations and biological activity. A search of the prior art and lack of written description in the instant disclosure indicate, absence evidence to the contrary, there is no Bacillus sp. having the claimed RNase III mutants having the desired biological activity.
While it is acknowledged that the declaration provides evidentiary support that identification of homologous RNase III mutants-having alanine substitution at conserved corresponding residues-is well within the routine skill of the art, there is no support for the claimed engineered bacteria derived from a wild type RNase III from a Bacillus sp. having the amino acids and the triple or quadruple mutants set forth in instant claim 1 and that upon expression it would cleave target dsRNA in to sRNA molecules of a discrete size capable of inducing RNA silencing in target pathogen without further experimentation.
Conclusion
See attached PTO-326 for disposition of claims.
THIS ACTION IS MADE FINAL. 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 Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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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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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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