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 .
This Office Action is in reply to Applicants’ correspondence of 11/03/2025.
Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicants’ amendments. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action.
This Action is made FINAL.
Please Note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Withdrawn Claim Rejections - 35 USC § 112 - Indefiniteness
The rejection of claim 18 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth on pages 2-3 of the Office Action of 08/01/2025 is withdrawn in light of the amendments to the claims.
Maintained Claim Rejections - 35 USC § 112 – Scope of Enablement
Modifies as Necessitated by Claim Amendments
Claims 16,19-23 and 25-32 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method of treatment of pathological cardiac hypertrophy and/or reducing the risk of pathological cardiac hypertrophy in a human subject, by administering to said human subject a pharmaceutical composition comprising a compound for promoting expression and/or activity of the long non-coding RNA (lncRNA) H19, wherein the compound is:
(a) a nucleic acid sequence which comprises or consists of the nucleic acid sequence encoding H19,
(b) an expression vector expressing the nucleic acid sequence as defined in (a), or
(c) a host comprising the expression vector of (b), and
wherein the expression of the nucleic acid sequence is under the control of a heart-specific promotor, and the nucleic acid sequence of the compound comprises SEQ ID NO: 12.
does not reasonably provide enablement for the methods as claimed that encompass any lncRNA H19 sequence for the treatment of a human subject. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Nature of the invention and breadth of the claims
The claims are directed to the treatment of cardiac hypertrophy, or reduction of the risk of cardiac hypertrophy, in a human subject. The claims broadly encompass the treatment of the human subject (as recited in the claims) with a nucleic acid that encodes any H19 gene (i.e.: an H19 gene from any non-human organism is encompassed by the treatments of the claims). The claims thus encompass a broad range of compositions, with a wide variety of sequences and non-established biological effects in humans, with a required functionality of treatment or risk reduction.
Direction provided by the specification and working example
The instant application teaches an analysis of gene expression of lncRNAs related to cardiac hypertrophy. The specification teaches (p.50; p.57) that in an analysis of heart tissue samples of TAC mouse model subjects, H19 was down regulated. The specification further teaches (p.60) that H19 is down regulated in a human hypertrophic heart tissue. The specification teaches (p.61) that overexpression of H19 under the control of a cardiac-specific promoter in a mouse model system can have beneficial effects; and that overexpression of H19 in a mouse cardiac cell line can have a beneficial effect on cell size (p.60).
The specification does not teach the analysis of any subject other than mouse or human. The specification does not teach any compositions other than nucleic acid systems for the increase of H19 expression. The specification does not teach any particular activities of H19 that are increased in the analysis of H19 expression in cells. The specification does not teach any lcRNA H19 sequence other than SEQ ID NO: 12 as relevant to human biology.
State of the art, level of skill in the art, and level of unpredictability
While level of skill in the art with regard to detecting an expression level of any particular nucleic acid sequence in sample is high, and the state of the art is advanced, the unpredictability in modifying the expression level of any particular nucleic acid for beneficial effects on a pathology in a particular orgnaism are greater. Such unpredictability is demonstrated by the related art.
Because the claims are directed to the treatment of human subjects, and encompass the use of an H19 lncRNA from any organism, while the specification teaches only analyses relevant to human and mouse, it is relevant to point out the unpredictability in correlating expression of genes among multiple different subject organisms with a particular phenotype. For example, sequences that appear quite similar may in fact have very different functionalities. Such a possibility is exemplified by Juppner (1995), which teaches that despite significant structural conservation, rat, opossum, and human PTH/PTHrP receptor homologs display distinct functional characteristics (Abstract; pp.39S-40S). It is unpredictable if, for example, the rat, mouse, or pig homologs of human H19 can be used to practice the invention in those or other organisms.
Relevant to this encompassed breadth of the claims (i.e.: treatment of a human with an H19 lcRNA from any non-human organism), Brannan et al (1990; cited on the IDS of 07/12/2022) provides that even in mammalian organisms such as human and mouse, the H19 lcRNA sequences shows regions which lack a high degree of conservation (e.g.: Fig. 1; p.29 - Comparison of the human and murine H19 genes).
Conclusion
Taking into consideration the factors outlined above, including the nature of the invention and scope of the claims, the state of the art and its high level of unpredictability, the lack of guidance by the applicant and the specific examples, it is the conclusion that an undue amount of experimentation would be required to use the invention as claimed in the full scope as claimed.
Withdrawn Double Patenting
The rejection of claims for issues related to double patenting, as set forth on pages 7-8 of the Office Action of 08/01/2025 is withdrawn in light of the terminal disclaimer filed on 11/03/2025, which is approved.
Conclusion
No claim is allowed.
Applicant's amendment necessitated any 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 STEPHEN THOMAS KAPUSHOC whose telephone number is (571)272-3312. The examiner can normally be reached M-F, 8am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at 571-272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683