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 .
Election/Restrictions
Applicant’s election without traverse of Group 1, claims 1, 6-9, 12, 14-15, 20-21, and 25-28; and Applicant’s species election of the method of claim 1(a) and the Cytor agonist of claim 1(i) in the reply filed on January 16, 2026 is acknowledged.
Claims 32-33 and 37-40 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Claims 9, 15, 20-21, and 26-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Claim 9 which is drawn to the RNA or nucleic acid molecule of claim 1, item (ii), and claims 15 and 21 which depend from claim 9, 20 are withdrawn based on Applicant’s election of the Cytor agonist of claim 1, item (i). Claims 20 and 26-28 are also withdrawn based on Applicant’s election of the Cytor agonist of claim 1, item (i).
Claims 1, 6-8, 12, 14, and 25 are examined on the merits.
Priority
The instant application is a 35 U.S.C 371 national stage filing of the International Application No. PCT/EP22/53229 filed on February 10, 2022. The instant application claims foreign priority under 35 U.S.C 119(a)-(d) to British Patent Applications GB2101932.8, filed on February 11, 2021. Receipt is acknowledged of a certified copy of the foreign patent application as required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 10, 2032 is in compliance with the provisions of 37 CFR 1.97 and is being considered by the examiner.
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.
Specification
The use of the term ThermoScientific Shandon Cryomatrix on pg. 83 and CRL-3216 on pg. 84, which are trade names or a marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 recites the term “hydridizing” on pg. 4, item (iii), line 6 which appears to be a typographical error misspelling hybridizing. Appropriate correction is required.
Claim 1 is objected to because of the following informalities: claim 1 recites “or” following part (e) and prior to “by administering the subject a Cytor agonist…”. For the purposes of examination, this is interpreted to be a typographical error. However, as instantly claimed, it could be interpreted that the administering step is an alternative to claim 1(e). Appropriate correction is required. It is recommended that Applicant amend the claim in order to remove the recitation of “or” following claim 1(e).
Claim Rejections - 35 USC § 112
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.
Claims 1, 6-8, 12, 14, and 25 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With regard to claim 1, the repeated use of the phrase "for example" (“e.g.”) renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). The dependent claims are included in the basis of this rejection because they do not clarify the scope of the claim. Appropriate correction is required.
With regard to claim 12, claim 12 recites the limitation "the agonist" in line 2. There is insufficient antecedent basis for this limitation in the claim as the there is no prior mention of an agonist. Prior recitations in claim 1 are to “a Cytor agonist”; thus, as claimed it is unclear whether the agonist is intended to refer to the Cytor agonist or another agonist. Appropriate correction is required.
With regard to claim 12, claim 12 recites the limitation wherein Cytor RNA is increased “directly”. The term “directly” is not defined by the claims, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As claimed, it is unclear how one having ordinary skill in the art would determine if Cytor RNA was increased directly. Appropriate correction is required.
With regard to claim 14, claim 14 recites the limitation "the agonist" in line 2. There is insufficient antecedent basis for this limitation in the claim as the there is no prior mention of an agonist. Prior recitations in claim 1 are to “a Cytor agonist”, thus as claimed it is unclear whether the agonist is intended to refer to the Cytor agonist or another agonist. Appropriate correction is required.
With regard to claim 25, claim 25 recites the limitation "the agonist" in line 2. There is insufficient antecedent basis for this limitation in the claim as the there is no prior mention of an agonist. Prior recitations in claim 1 are to “a Cytor agonist”, thus as claimed it is unclear whether the agonist is intended to refer to the Cytor agonist or another agonist. Appropriate correction is required.
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, 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 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 1, 7-8, 12, 14, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (2020, LncRNA CYTOR attenuates sepsis‐induced myocardial injury via regulating miR‐24/XIAP. Cell Biochem. and Funct., 38(7), 976-985, found in IDS, hereafter “Chen”) in view of Mammalian Gene Collection (MGC) Program Team (2002, Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. PNAS, 99(26), 16899-16903, hereafter “MGC Program Team”) and as evidenced by National Library of Medicine entry, SNP 7436072 (NIH National Library of Medicine, SNP 74360724, https://www.ncbi.nlm.nih.gov/snp/?term=74360724, retrieved February 19, 2026).
With regard to claims 1 and 14, Chen teaches that upregulation of the long noncoding RNA Cytor via administration of a Cytor overexpression plasmid (Pg. 977, left col., 4th para.), i.e. a Cytor agonist, is protective against sepsis-induced myocardial injury in human cardiomyocytes (Pg. 979, Section 3.2) and in a rat model (Pg. 981, Section 3.6). Thus, Chen provides support for treatment of a subject having sepsis with a Cytor agonist. Chen is silent as to Cytor RNA promoting myogenesis in skeletal muscle, however, promotion of myogenesis in skeletal muscle appears to be an inherent property of Cytor RNA.
MPEP 2112.01(II) states:
“’Products of identical chemical composition can not have mutually exclusive properties.’ In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
MPEP 2112(I) states:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
As Chen teaches Cytor RNA overexpression for use in sepsis-induced myocardial injury in both rats and human cardiomyocytes, the Cytor RNA as taught by Chen and the instantly claimed Cytor RNA appear to be the same composition. Thus, the ability of Cytor RNA to promote myogenesis in skeletal muscle is considered to be an previously unknown inherent property of Cytor RNA.
Chen is silent as to the sequence of Cytor RNA in the Cytor overexpression plasmid.
MGC Program Team teaches characterization of an RNA sequence for human non-protein coding RNA 152 and entry of that sequence into the Mammalian Gene Collection program (Abstract). The RNA sequence for human non-protein coding RNA 152 as taught by MGC Program Team has 88% sequence identity to instantly claimed SEQ ID NO: 1 (see sequence search 02/04/2026, SEQ ID NO:1, .rge file, result 4). It was well known that human Cytor is also known as non-protein coding RNA 152 (see Pg. 8 of Applicant’s specification), thus a skilled artisan would have recognized that non-protein coding RNA 152 and Cytor were alternate names for the same molecule.
Further, the instant claims recite RNA comprising “a nucleotide sequence as set forth in any one of SEQ ID NOs: 1-15 or a nucleotide sequence with at least 80% sequence identity to a sequence…”. According to Technology Center 1600 procedure the examiner is instructed to interpret this type of claim language broadly: Claim language such as claims 1 and 14 encompass nucleotide sequences that comprise the full-length sequence of SEQ ID NOs: 1-15 or any portion of SEQ ID NOs: 1-15. This claim is made obvious by any nucleic acid comprising any dinucleotide or larger oligonucleotide which is a portion of SEQ ID NO:1-15. If claims 1 and 14 were amended to recite RNA comprising “the nucleotide sequence as set forth in any one of SEQ ID NOs: 1-15 or the nucleotide sequence with at least 80% sequence identity to the sequence…,” the examiner would interpret the claims to encompass only nucleotide sequences that comprise the full length of SEQ ID NOs: 1 -15 or having 80% sequence identity with the full length of SEQ ID NOs: 1-15, with or without additional nucleotides at either or both ends.
Therefore, it would have been obvious to one having ordinary skill in the art, before the effective filing date of the claimed invention, to choose the RNA sequence encoding non-protein coding RNA 152 (i.e., Cytor) as taught by MGC Program Team for use in the method of treating a subject having sepsis by administration of Cytor RNA as taught by Chen with a reasonable expectation of success. A skilled artisan would have been motivated to choose the RNA sequence encoding non-protein coding RNA 152 (i.e., Cytor) as taught by MGC Program Team for use in the method of treatment as taught by Chen as it was a known characterized sequence freely available in the Mammalian Gene Collection database and was known to encode the same molecule as taught by Chen.
With regard to claim 7, Chen is silent as to a subject being heterozygous or homozygous for the G allele of cis-eQTL rs74360724. However, the National Library of Medicine entry for SNP 74360724 evidences that, in most populations, the G allele is the major allele and would be present in greater than 50% of the population. In particular, since Chen’s group studying sepsis-induced myocardial injury in the Intensive Care Unit at a hospital in China and the National Library of Medicine entry for SNP 74360724 evidences that in other Asiatic populations, the G allele is present in upwards of 80% of the population (see entry for TOMMO, Korea4K, and KOREAN), a skilled artisan interested in treatment of sepsis-induced myocardial injury would have a much larger chance of patients being heterozygous or homozygous for the G allele of cis-eQTL rs74360724. Therefore, a skilled artisan would realize that being heterozygous or homozygous for the G allele of cis-eQTL rs74360724 would be an inherent property the majority of human subjects. Thus, it is more likely than not that any given sepsis-induced cardiomyopathy patient treated by upregulating Cytor RNA would be heterozygous or homozygous for the G allele of cis-eQTL rs74360724.
With regard to claim 8, Chen teaches that rats having sepsis-induced cardiomyopathy exhibit decreased activity, slow movement, and decreased response to stimuli (Pg. 977, section 2.1), which is considered to reasonably read on subjects who are inactive.
With regard to claim 12, Chen teaches that administration of the Cytor overexpression plasmid is via caudal vein injection (Pg. 977, Section 2.1) which a skilled artisan would recognize as systemic administration resulting in widespread delivery of the Cytor overexpression plasmid, including to skeletal muscle, which is considered to reasonably read on increasing the amount of Cytor RNA in skeletal muscle directly.
With regard to claim 25, as detailed above, Chen teaches upregulation of Cytor RNA expression via systemic administration of a Cytor overexpression plasmid, i.e. a Cytor agonist. Although Chen is silent as to inhibition of degradation of endogenous Cytor, one having ordinary skill in the art would recognize that increasing the amount of exogenous Cytor RNA would increase the amount of Cytor RNA substrate present in the degradation pathway and therefore would naturally result in the inhibition of the degradation of endogenous Cytor RNA.
Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Chen and MGC Program Team as applied to claim 1 above, and in further view of Schefold et al. (2010, Intensive care unit-acquired weakness (ICUAW) and muscle wasting in critically ill patients with severe sepsis and septic shock. J. of Cachexia, Sarcopenia and Muscle, 1(2), 147-157, hereafter “Schefold”).
With regard to claims 6 and 8, as detailed above the combination of Chen and MGC Program Team teaches use of Cytor RNA having a sequence with over 80% sequence identity to instantly claimed SEQ ID NO: 1 for use in treating sepsis-induced myocardial injury both in human cardiomyocytes and in a rat model of sepsis.
Although Chen teaches that rats having sepsis-induced cardiomyopathy exhibit decreased activity, slow movement, and decreased response to stimuli (Pg. 977, section 2.1), Chen is silent as to skeletal muscle atrophy and inactivity or immobilization.
Schefold teaches that sepsis is associated with muscle wasting which involves atrophy of skeletal muscle fibers and is accompanied by prolonged immobilization (Section 2.1), which is considered to reasonably read on subjects having or being at risk of skeletal muscle atrophy and subjects who are immobile.
Chen teaches that sepsis-induced cardiomyopathy is a common complication during sepsis which occurs in about 40% of patients and that treatment of sepsis-induced cardiomyopathy reduces patient mortality (Pg. 976, left col., 1st para.). Therefore, one having ordinary skill in the art would have recognized that a sizable population of patients experiencing sepsis also would experience sepsis-induced myocardial injury and would be expected to exhibit a prolonged recovery, putting them at risk of longer term hospitalization and thereby skeletal muscle atrophy and immobilization. Therefore, it would have been obvious before the effective filing date of the claimed invention, to choose the population of subjects experiencing a prolonged recovery from sepsis-induced myocardial injury who are at risk of skeletal muscle atrophy and would be likely to be immobile as taught by Schefold for use in the method of treating sepsis-induced myocardial injury via upregulation of Cytor RNA as taught by Chen with a reasonable expectation of success. One having ordinary skill in the art would have been motivated to make this combination since Chen teaches that timely and effective treatment of sepsis-induced myocardial injury, a common complication of sepsis, is important for reduction of patient mortality.
Conclusion
No claims are allowed.
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/ERIN V PAULUS/Examiner, Art Unit 1631
/ARTHUR S LEONARD/Examiner, Art Unit 1631