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 .
DETAILED ACTION
Claim status
Claims 203-222 are pending
Claims 203-222 under examination
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/12/2025 and 12/30/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112(b)
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.
Claim 222 is 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 pre-AIA the applicant regards as the invention.
Claim 222 is directed to the synthetic RNA “of claim 1”. There is insufficient antecedent basis for this limitation in the claim because Claim 1 is cancelled, thereby rendering Claim 1 incomplete. In light of the specification and for the sake of compact prosecution, Claim 222 is being interpreted as dependent on Claim 203. Appropriate correction is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 203-211, 214-217, 219, 221 and 222 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rossi (WO2014/153069, published 9/25/2014, filed 3/14/2014, with priority to US 61/782,037 filed 3/14/2013)
In regard to claim 203, Rossi claims a composition comprising a modified (synthetic) mRNA, where each uracil of said modified mRNA sequence is a modified uracil (Claim 34 of priority document). In regard to the modified uracil, Rossi claims the modified uracil is 5-hydroxyuridine (Claim 37 of priority document). Finally, Rossi explains that the claimed mRNA encoded reprograming factors for inducing hematopoietic stem cells (HSC), wherein these mRNA include the necessary elements for mRNA stability and translation in the HSCs including a 5’Cap, 5’UTR with Kozak initiation sequence, 3’UTR with a poly(A) tail ([00220-00222] of priority document).
In regard to claims 204-209, as stated supra, Rossi claims each uracil of said modified mRNA sequence is modified, and Rossi claims the modified uracil is 5-hydroxyuridine. Thus, Rossi teaches 100% of the uridines are modified to 5’hydroxyuridine.
In regard to claim 210, as stated supra, Rossi claims the mRNA encodes a reprogramming factor.
In regard to claim 211, Rossi claims the reprogramming factors ZFP37, HOXB4, and HFL, which are transcription factors.
In regard to claim 214, Rossi explains that “modified mRNA” refers to an RNA molecule produced according to in vitro techniques ([0097] of priority document), and also teaches the chemical synthesis technique is in vitro transcription ([0081] of priority document).
In regard to claim 215, Rossi further claims that each cytosine of said modified mRNA is a modified cytosine, which include 5-formylcytidine and 5’hydroxymethylcytidine (Claims 34 and 37 of priority document)
In regard to claims 216 and 219, as stated supra, Rossi teaches mRNA includes the necessary elements for mRNA stability and translation including a 5’Cap, Kozak initiation sequence, and poly(A) tail.
In regard to claim 217, Rossi teaches the ultimate 5’nucleotide contains a Cap1 structure ([00222] of priority document).
In regard to claim 221, Rossi teaches the poly(A) is at least 40 nucleotides in length ([00222] of priority document).
In regard to claim 222 as stated supra, Rossi teaches mRNA composition is for inducing HSCs and explains that this composition is prepared as an emulsion for delivery with pharmaceutical excipients ([0261] of priority document).
Accordingly, Rossi anticipates instant claims.
Claim Rejections - 35 USC § 103
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 of this title, 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 218 and 220 are rejected under 35 U.S.C. 103 as being unpatentable over Rossi (WO2014/153069, filed 3/14/2014, with priority to US 61/782,037 filed 3/14/2013), in view of Schrum et al., (US 2012/0251618, filed 4/02/2012).
As stated supra, Rossi teaches and claims a composition comprising a synthetic mRNA comprising each uridine replaced with 5-hydroxyuridine, and a 5’ UTR and 3’UTR.
However, Rossi is silent to UTR’s belonging to alpha and beta globin.
Schrum teaches modified mRNA (mmRNA) compositions for expressing a polypeptide of interest in a cell, wherein the mmRNA comprising a 5’Cap1 and polyA tail, and the modified nucleotides is 5-hydroxyuridine (see claims 1, 2, and 19 of Schrum). In regard to claims 218 and 220, Schrum teaches the mmRNA comprises the beta-globin upstream region (i.e., 5’UTR) and an alpha-globin 3’UTR [0353-0354].
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to prepare the modified mRNA comprising a 5’UTR and 3’UTR as taught by Rossi, and choose the beta-globin 5’UTR and alpha-globin 3’UTR as taught by Schrum with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Schrum because these are beneficial for the mmRNA [0071].
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 203-209, 211-213, 216 and 219 are rejected under 35 U.S.C. 103 as being unpatentable over Glucksmann et al., (WO2015/048577, filed 9/26/2014, with priority to US provisional 61/898,043 filed 10/31/2013)
In regard to claims 203, 211-213, Glucksmann teaches and claims a composition comprising a synthetic mRNA that encodes the gene-editing protein Cas9 that allows transient expression of the nuclease in a cell (p. 9, last para., p. 65, Table V-1a, last line, p. 66, Table V-1b, last line, p.188, 7th para., see also claims 117-118 of ‘043 priority document).
In regard to the synthetic mRNA as per claims 203 and 204-209, Glucksmann teaches that 100% of the mRNA is modified so as to introduce stability and reduce the innate immune response (pgs. 171, last three para. to 172 1st para., of ‘043 priority document), and teaches the modified nucleotide is 5-hydroxyuridine p. 175, last para. of ‘043 priority document).
Finally, in regard to the untranslated regions and claims 203, 216 and 219, Glucksmann teaches a Kozak sequence and polyadenylation signals (p. 67, 2nd to last para. of ‘043 priority document), which would comprise part of a 5’UTR and 3’UTR, respectively.
However, Glucksmann is silent to a preferred embodiment of a Cas9 mRNA with a 5’ Kozak and 3’ polyA comprising 100% modified 5-hydroxyuridines.
Nevertheless, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to prepared said modified mRNA because each of the individual elements of the instant claims are independently presented by Glucksmann as embodiments and are taught that they can be combined in various embodiments; therefore a combination of all the elements into a single embodiment would be apparent to an artisan skilled in gene therapy in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)). Regarding the rationale for combining prior art elements according to known methods to yield predictable results, all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of filing of the invention. Each of the elements (Cas9 mRNA, 100% modified mRNAs to best improve stability and reduce innate immunity, and 5-hydroxyuridine modified nucleotides) are taught by Glucksmann and further they are taught in various combinations and are shown to be used in a method for producing recombinant Cas9 in a cell. It would be therefore predictably obvious to use a combination of these elements in said composition.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 203-209, 211, 214-216, 221-222 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 156-160, 162-170 of copending Application No. 19/028,477. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the composition comprising a modified RNA with a 5’ and 3’ UTR and one or more 5-hydroxyuridine, 5-hydroxymethyluridine, 5-carboxyuridine, and/or 5-formlyuridinet of cited application makes obvious the composition of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the instant application claims are more specific with respect to the % modification.
Nevertheless, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to claim at least 50% or more modification, since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233.
Furthermore, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to claim the modified RNA in a pharmaceutical composition comprising an excipient, in order to allow its use with cells or in a subject.
Since the instant application claims are obvious over cited application claims, said claims are not patentably distinct.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763
. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ARTHUR S LEONARD/Examiner, Art Unit 1631
Prosecution Insights