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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/21/2026 has been entered.
Claim Status
Currently, claims 1, 3-5, 7-10, 12-14, 16-21 are pending in the instant application. Claims 2, 6, 11, and 15 have been canceled. This action is written in response to applicant’s correspondence submitted 01/21/2026. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is Non-Final.
Withdrawn Rejections
The rejection of claims 1, 3-5, 7-10, 12-14, 16-21 under 35 USC 112(b) is withdrawn in view of the amendment to the claims.
The rejection of claims 1, 3-5, 7-9 under 35 U.S.C. 102(a)(1) as being anticipated by Fotin-Mleczek et al. (US20190241633A1) is withdrawn in view of the amendment to the claims.
Maintained Rejections
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, 7-10, 12-14, 16-21 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. This is a written description rejection. This rejection was previous presented and has been rewritten to address the amendment to the claims.
The claims are drawn to a composition (claim 1, 3-5, 7-9) and methods of administering a composition comprising at least one isolated nucleoside modified RNA molecule comprising SEQ ID NO 3 or SEQ ID NO 4 (claims 10, 12-14, 16-21). SEQ ID NO 3 comprises PDGF-2 and SEQ ID NO 4 comprises BMP-2. Claims encompass a composition comprising at least one nucleoside modified RNA molecule transcribed from a sequence comprising SEQ ID NO3 and SEQ ID NO 4, wherein the composition induces periodontal ligament cell proliferation, promotes endothelial cell tube formation or combination thereof. Claims further include methods of administering a composition comprising at least one nucleoside modified RNA molecule transcribed from a sequence comprising SEQ ID NO3 and SEQ ID NO 4. The recitation of transcribed from “a sequence” encompasses any two or more nucleotides of SEQ ID NO 3 and two or more nucleotides of SEQ ID NO 4. The amended claims encompass not only the full length sequence of SEQ ID NO 3 and SEQ ID NO 4 but also fragments of any two or more nucleotides of SEQ ID NO 3 and SEQ ID NO 4.
The specification teaches the sequences of SEQ ID NO 1 and 3 for PDGF-BB and SEQ I DNO 2 and 4 BMP-2. However the specification does not disclose that SEQ ID NO 3 and 4 can induce regeneration of periodontal tissue or bone. The specification does not describe any sequence, including SEQ ID NO 3 and 4 that would induced regeneration of periodontal tissue or bone. Additionally the specification does not disclose the functionality of SEQ ID NO 3 and SEQ ID NO 4. The specification does not teach any fragment of SEQ ID O 3 or SEQ ID NO 4 of a sequence transcribed from SEQ ID NO3 or SEQ ID NO 4.
Thereby, while the specification has adequately described PDGF-V and BMP-2 to induce regeneration of periodontal tissue, the specification has not adequately described the optimized DNA sequence encoding the nucleoside modified RNA of SEQ ID NO 3 or SEQ ID NO 4 or any sequence of two or more nucleotides transcribed from SEQ ID NO3 or SEQ ID NO4 that would induce regeneration of periodontal tissue or bone.
No additional members of the claimed genus of RNA encoding growth factors, fragments or variants have not been sufficiently described in terms of any other relevant identifying characteristics. Relevant to the lack of particular structural limitations in the rejected claims, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, the specification does not disclose a clear structure-function relationship between the claimed RNA with the claimed function of induces periodontal ligament cell proliferation, promotes endothelial cell tube formation or combination thereof or with periodontal tissue regeneration. There is no showing or evidence which links particular nucleotide locations of SEQ ID NO 3 or 4 with induces periodontal ligament cell proliferation, promotes endothelial cell tube formation or combination thereof . While the specification teaches a structure-function relationship for isolated RNA encoding PDGF-BB and BMP-2 with periodontal tissue regeneration there is no indication that this structure function relationship occurs in nucleoside modified RNA molecule transcribed from SEQ ID NO 3 and 4 or PDGF-BB and BMP2. In the absence of any real structure-function relationship in modified RNA molecule transcribed form SEQ ID NO 3 and 4 and in the absence of a representative number of species of the claimed genus of modified nucleosides, there is insufficient descriptive support for the currently claimed genus of compositions comprising isolated RNA encoding growth factor variants and fragments thereof that have the property of inducing periodontal tissue or bone regeneration. While limitations from the specification are not read into a claim, a claim must be read in view of the specification.
It is acknowledged that the specification also teaches the general methodology for detecting mutations and variants in growth factors. However, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. Thereby, a showing of how to potentially identify variants and fragments of growth factors is not sufficient to establish that Applicants were in possession of the invention as broadly claimed.
With respect to the present invention, there is no record or description which would demonstrate conception of SEQ ID NO 3 and 4 with the function of induces periodontal ligament cell proliferation, promotes endothelial cell tube formation or combination thereof and associated with inducing regeneration of periodontal tissue or bone. The specification does not disclose a representative number of fragments or variations within PDGF-BB or BMP2 that are linked to regeneration of periodontal tissue or bone. Therefore, the claims fail to meet the written description requirement because the claims encompass a significantly large genus of growth factors, variants and fragments which are not described in the specification that would be associated inducing regeneration of periodontal tissue or bone.
Response to Arguments
The response traverses the rejection on pages 5-6 of the remarks mailed 01/21/2026. The response asserts the claims have been amended to recite a composition comprising at least one isolated nucleoside-modified RNA molecule transcribed from a sequence selected from the group consisting of SEQ ID NO 3 and SEQ ID NO 4. The response asserts that SEQ ID NO 3 and 4 can be found on page 15 through 17 of the specification and therefore are described.
This response has been thoroughly reviewed but not found persuasive. While the specification provides the sequence of SEQ ID NO 3 and SEQ ID NO 4 on pages 15-17 this does not provide description for an RNA modified nucleoside transcribed by SEQ ID NO3 and 4 with the recitation function. The specification does not describe the use of SEQ ID NO 3, SEQ ID NO 4, for the claimed function. The examples do not describe that SEQ ID NO 3 and SEQ ID NO 4 are the sequences being used for the examples. Additionally as amended the claims encompass any two or more nucleotides of SEQ ID NO 3 or SEQ ID NO 4 and the specification does not disclose any fragments that encompass the recited functions. As such the specification has not describes a composition comprising SEQ ID NO 3, 4 that is capable of inducing periodontal ligament cell proliferation or promotes endothelial cell tube formation. For these reasons and reasons of record this rejection is maintained.
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 1, 3-5, 7-10, 12-14, 16-21 are rejected under 35 U.S.C. 103 as being unpatentable over Elangovan (US20160220698 A1) in view of Fotin-Mleczek et al. (US20190241633A1).
Elangovan teaches a method to enhance tissue regeneration and bone regeneration using compositions comprising modified RNA encoding BMP2 and PDGFB into cells for tissue engineering application (See para 19). Elangovan teaches the defect is a jaw bone and the administration of the compositions increased bone regeneration. Elangovan teaches the mammal is in need of periodontal regeneration (see para 9). Elangovan teaches a method of administering a composition comprising a RNA encoding PDGF or BMP (see para 9). Elangovan teaches administering in vivo an effective compositions to a tissue of a mammal (see claim 17 and 19 of ‘069). Elangovan teaches compositions comprising modified RNA encoding BMP2 into cells for tissue engineering application (See para 19).
With regard to claim 3-5 and 11-14, Elangovan teaches RNA molecules comprising 1-methyl pseudo uridine (see para 20). Elangovan teaches modified RNA is purified (see para 115).
With regard to claim 7-8 and 16-17, Elangovan teaches the RNA in complexed with a polymer nanoparticle, including lipids (see para 6, 51, 54).
With regard to claim 9, 18 and 21, Elangovan teaches the composition comprises a scaffold (see para 59-60 and para 86).
With regard to claim 19, Elangovan teaches administering single and different compositions to animals (see para 127).
Elangovan does not teach the sequence for PDGF or BMP2 and therefore does not teach SEQ ID NO 3 or SEQ ID NO 4.
However, it was known in the art to increase CG optimization of an RNA sequence for human codon usage and optimization for gene therapy (See para 30-31). Fotin-Mleczek teaches the sequences of the RNA, preferably mRNA may be modified and stabilized by modifying the G/C content, particularly increased compared to the G/C content of the wild type RNA (See para 138 and 149). Fotin-Mleczek teaches SEQ ID NO 40356 and SEQ ID NO 47442. SEQ ID NO 40356 is 90% identical to SEQ ID NO 4 and SEQ ID NO 47422 is 90% identical to SEQ ID NO 3. Fotin-Mleczek teaches BMP2 is SEQ ID NO 40356 (pg. 74) and PDGFB is SEQ ID NO 47442(pg253). Fotin-Mleczek teaches RNA molecules comprising 1-methyl pseudo uridine (see para 130). Fotin-Mleczek teaches modified RNA is purified (see instant claim 1 and para 330).Fotin-Mleczek teaches the RNA in complexed with a polymer nanoparticle, including lipids (see para 136).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to improve the composition and method of inducing regeneration of periodontal tissue using BMP2 and PDGF, as taught by Elangovan to include CG optimized mRNA sequences of BMP2 and PDGF, as taught by Fotin-Mleczek, to improve the method by Elangovan and include stabilized and optimized sequences. The ordinary artisan would have been motivated to improve the composition of using BMP2 and PGDF and method of using is taught by Elangovan with the composition and method of codon optimization of mRNA for gene therapy of BMP2 and PGDF as taught by Fotin-Mleczek because Fotin-Mleczek teaches an optimized mRNA sequence for gene therapy for BMP2 and PGDF comprising SEQ ID NO 40356 and 47442 that is 90% identical to SEQ ID NO 3 and SEQ ID NO 4. The ordinary artisan would have had a reasonable expectation of success that the use of SEQ ID NO 40356 and 47442 could be used in the method of Elangovan et al. because Elangovan teaches using RNA comprising BMP2 and PGDF for inducing regeneration of periodontal disease and Fotin-Mleczek teach that the sequence of BMP2 and PGDF for gene therapy and RNA compositions.
Because both Elangovan and Fotin-Mleczek et al. teach RNA compositions comprising lipid nanoparticles and modified 1-methyl-pseudouridine of BMP2 and PGDF for therapy, it would have been obvious to one skilled in the art to substitute one component, RNA of BMP2 and PGDF as taught by Elangovan with sequences of SEQ ID NO 40356 and 47422 as taught by Fotin-Mleczek, in order to achieve the predictable result of inducing regeneration of periodontal tissue.
Response to Arguments
The response traverses the rejection in the remarks mailed 01/21/2026 on pages 8-11. The response asserts that the rejection of the claims under 103 could only have been made with hindsight bias and ex post reasoning. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In the instant case, the test for obviousness is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case the combined teachings of Elangovan and Fotin-Mleczek render obvious the claimed invention.
The response asserts that in order for claims 1, 3-5, 7-10, 12-14 and 16-21 to render obvious the claims the combination of Elangovan and Fotin-Mleczek must teach or suggest each and every element of the claims. The response asserts there is nothing in the cited references that would motivate one of ordinary skill in the art to combine with a reasonable expectation of success the teaching of the references to produce the presently claimed invention. The response asserts that even with codon optimization there are a wide range of optimization tools to select from that use different approaches and person of ordinary skill in the art would generate an unknown number of potential optimized alternatives and this does not demonstrate a finite number of identified predictable optimized sequences. The response asserts that a person of skill in the art provided with sequences of Fotin-Mleczek and multitude of optimization methods in the art would still have had to select and apply appropriate optimization tools with appropriate inputs and constraints to arrive at the sequences of SEQ I DNO 3 and SEQ ID NO 4. This response has been thoroughly reviewed but not found persuasive. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation (see MPEP 2144). Based on the general knowledge available to one of ordinary skill in the art, the ordinary artisan would have been motivated to design and test the optimized sequences to obtain additional modified RNAs that function to induce regeneration of periodontal tissue or bone and identify RNA with improved properties, including SEQ ID NO 3 and SEQ ID NO 4. Because the art of Elangovan teaches modified RNA encoding PDGF or BMP2 to enhance tissue regeneration and bone regeneration, it would have been obvious to the ordinary artisan to generate modified RNA sequences encoding PDGF and BMP2 including SEQ ID NO3 and SEQ ID NO 4 based on the guidance provided by Fotin-Mleczek. Furthermore, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that was not of innovation but of ordinary skill and common sense. See KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In the instant case, generating nucleoside modified RNA from a sequence of SEQ ID NO 3 or SEQ ID NO4 to induce regeneration of periodontal tissue is within the technical grasp of an ordinary artisan based on the teaching of Fotin-Mleczek and Elangovan, and the general state of the art with regard to codon optimization including using known software tools and algorithmic strategies as asserted by applicants. Therefore, absent secondary consideration such as evidence demonstrating unexpected results of SEQ ID NO 3 and SEQ ID NO 4, the ordinary artisan would have designed additional RNA sequences including SEQ ID NO 3 and SEQ ID NO 4 by codon optimization to induce regeneration of periodontal tissue, as demonstrated in the prior art. For these reasons and reasons of record this rejection is maintained.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to whose telephone number is. The examiner can normally be reached M-F 9a-4p.
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, Fereydoun Sajjadi can be reached at 571-272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699
Prosecution Insights