DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 13 July 2026 have been entered. Claims 1-13 were previously pending in the application. No claims have been cancelled, and no new claims have been added by Applicant. Claims 1-13 are currently pending in the application. Claims 1, 6, 12, and 13 are independent claims.
The following election of species remains in effect in the instant application:
Insertion positions: a. Amino acid No. 587,
Inserted amino acid sequences: a. SEQ ID NO: 1.
Claims 1-13 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Species Election
Applicant argues that “Assuming that the search was conducted and no prior art was found as to the elected species, the non-elected species must be rejoined.” However, this is not agreed.
Note that, as discussed in the Requirement for Restriction/Election, that “Upon the allowance of a generic claim, Applicant will be entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitation of an allowed claim.” Neither independent claim 1 nor independent claim 12 are in condition for allowance with respect to the elected species. As such, no rejoinder is required.
Additionally, to the extent that Applicant is referring to the handling of species elections for Markush claims, note that the recitation of alternatives within independent claims 1 and 12 are not structured as a Markush group. “A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members” [MPEP 2173.05(h)(I)] and “A claim element defined by selection from a group of alternatives (a Markush grouping; see MPEP §§ 2117 and 2173.05(h)) requires selection from a closed group "consisting of" (rather than "comprising" or "including") the alternative members.“ [MPEP 2111.03(II)]. The alternatively recited options within independent claims 1 and 12 are not recited as being “selected from a group consisting of” (or the like) and so are not considered to be a Markush group. Therefore, rejoinder is not required upon a lack of prior art rejection over the elected species wherein other rejections are outstanding.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2021/054347, filed 22 February 2021, which claims priority to EPO 20158633, filed 20 February 2020. Filing of a certified copy of the EPO 20158633, filed 20 February 2020is acknowledged.
Thus, the earliest possible priority for the instant application is 20 February 2020.
Information Disclosure Statement
The information disclosure statement filed 13 July 2026 has been considered by the Examiner.
37 CFR 1.121
The substitute specification filed 13 July 2026 has not been entered because it does not
conform to 37 CFR 1.121(b) and (c) because: the marked up copy of the amended specification filed 13 July 2026 includes tracked changes, which is not an allowed amendment format. See MPEP
608.04(q), which states, “A marked-up copy of the substitute specification showing all the changes
relative to the immediate prior version of the specification of record must also be submitted. The text of
any added subject matter must be shown by underlining the added text. The text of any deleted matter
must be shown by strike-through except that double brackets placed before and after the deleted
characters may be used to show deletion of five or fewer consecutive characters. The text of any
deleted subject matter must be shown by being placed within double brackets if strike-through cannot
be easily perceived. Numbering the paragraphs of the specification of record is not considered a change
that must be shown under 37 CFR 1.125(c). The paragraphs of any substitute specification, other than
the claims, should be individually numbered in Arabic numerals (for example [0001]) so that any amendment to the specification may be made by replacement paragraph in accordance with 37 CFR
1.121(b)(1).”
The claim amendment filed 13 July 2026 is objected to under 37 CFR 1.121(c) because
Applicant’s claim listing is not in compliance with 37 CFR 1.121(c) which states that the claim listing must
provide the status of all claims, that all claims being currently amended in an amendment paper shall be
presented in the claim listing, indicate a status of "currently amended," and be submitted with markings
to indicate the changes that have been made relative to the immediate prior version of the claims, and
that the text of all pending claims not being currently amended shall be presented in the claim listing in
clean version, i.e., without any markings in the presentation of text. The presentation of a clean version
of any claim having the status of "original," "withdrawn" or "previously presented" will constitute an
assertion that it has not been changed relative to the immediate prior version, except to omit markings
that may have been present in the immediate prior version of the claims of the status of "withdrawn" or
"previously presented."
Specifically, independent claim 1 is marked “Currently Amended” and comprises markings
indicating insertions and/or deletions from the previous version. However, the amended claim also
comprises a vertical line in the left margin such as from “tracked changes” in a document, which is not an allowed amendment format.
In the interests of compact prosecution, the claim listing has been entered. However, future
claim listings must include the correct status of all claims, including appropriate mark-ups for changes to
the claims, in order for the claim listing to meet the requirements for entry under 37 CFR 1.121(c) or a
Notice of Non-Compliant Amendment will be mailed to applicant.
Specification
The objection to the specification of the disclosure for the Brief Description of the Drawings does not include a description of each panel and reciting trade names and/or marks without the corresponding symbols and/or generic terminology is maintained in view of the amendment to the specification filed 13 July 2026 having not been entered, as discussed above.
Claim Rejections - 35 USC § 112(b)
The rejection of amended and previously presented claims 1-13 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for multiple issues of indefiniteness is maintained. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended independent claim 1 to address some of the issues of indefiniteness identified in the prior action, including for reciting “a nucleic acid construct for an effector molecule”, and for reciting “AAV2 viral vector particle comprising a nucleic acid construct for an effector molecule, comprising a capsid protein (CAP)”. However, independent claim 1 still recites “comprising SEQ ID NO: 1” in line 5, which is indefinite because it is unclear how a capsid protein can comprise a sequence identifier itself rather than the sequence of the sequence identifier.
Additionally, none of claims 2-13 were amended to address the issues identified with claims 5, 6, 7, 8, 9, 10, and 12 in the prior action.
Note that the amendment to claim 1 to recite, “wherein said inserted amino acid section is inserted C-terminally to amino acid No. 587, No. 588 or No. 453 of SEQ ID NO: 56” does not overcome the issue of indefiniteness wherein claim 5 conflicts with claim 1. Although claim 1 no longer recites “C-terminally to amino acid No. 587 or No. 588 or No. 453 of the wild-type amino acid sequence of CAP of SEQ ID NO: 56”, the claim as written still requires that the inserted amino acid section be inserted into a CAP protein having the sequence according to SEQ ID NO: 56, and not merely into any CAP protein wherein the numbering of the protein is according to SEQ ID NO: 56.
Note also that the amendment to independent claim 1 to recite “a nucleic acid construct encoding an effector molecule” has not clarified the issues of previously presented claims 7 and 8 wherein it is unclear whether the nucleic acid construct of claims 7 and 8 is the same nucleic acid construct recited in claim 1.
As such, the metes and bounds of the claims still cannot be determined.
Applicant argues that the amendments to independent claim 1 addresses the rejection, and thus the rejection must be withdrawn. However, this is not agreed.
As discussed above, Applicant addressed some of the issues of indefiniteness identified in the prior action. However, Applicant did not address all of the issues of indefiniteness identified for the claims, including issues with independent claims 1 and 12. Therefore, Applicant’s arguments do not overcome a finding of indefiniteness under 35 U.S.C. 112(b), and the rejection is maintained.
Claim Rejections - 35 USC § 112(a)
The rejection of amended and previously presented claims 1-13 under 35 U.S.C. 112(a) for the specification, while being enabling for:
An AAV2 viral vector particle comprising:
a nucleic acid construct comprising an expression cassette encoding an effector molecule, and
a capsid protein (CAP) which comprises an insert amino acid sequence C-terminal to amino acid No. 587 of the CAP wild-type amino acid sequence according to SEQ ID NO: 56, wherein the insert amino acid sequence comprises:
an N-linker AAA or ASA amino acid sequence immediately C-terminal to amino acid No. 587,
the sequence of SEQ ID NO: 1 immediately C-terminal to the N-linker sequence, and
a C-linker AA amino acid sequence immediately C-terminal to the sequence of SEQ ID NO: 1,
wherein the effector molecule is long noncoding RNA (lncRNA) H19, and
wherein the AAV2 viral vector particle is for administering to treat a disease or defect of cardiac myocytes, and
wherein the disease or defect of cardiac myocytes is pathological cardiac hypertrophy;
A process for producing AAV2 viral vector particles, comprising:
delivery of components for AAV vector production in a cultivated eukaryotic HEK293 cell, followed by
cell lysis and removal of cellular components and plasmid DNA, and
further purification of AAV viral vector particles,
wherein the AAV2 viral vector particle comprises:
a nucleic acid construct comprising an expression cassette encoding an effector molecule, and
a modified capsid protein (CAP) which comprises an insert amino acid sequence C-terminal to amino acid No. 587 of the CAP wild-type amino acid sequence according to SEQ ID NO: 56, wherein the insert amino acid sequence comprises:
an N-linker AAA or ASA amino acid sequence immediately C-terminal to amino acid No. 587,
the sequence of SEQ ID NO: 1 immediately C-terminal to the N-linker sequence, and
a C-linker AA amino acid sequence immediately C-terminal to the sequence of SEQ ID NO: 1,
wherein the effector molecule is long noncoding RNA (lncRNA) H19, and
wherein the AAV2 viral vector particle is adapted for administering to treat a disease or defect of cardiac myocytes,
wherein the disease or defect of cardiac myocytes is pathological cardiac hypertrophy,
wherein the components for AAV vector production comprise:
an AAV helper plasmid comprising a nucleic acid sequence encoding
the modified CAP protein, and
a wild-type AAV2 Rep proteins,
an adenoviral helper plasmid, and
an AAV vector genome plasmid comprising the nucleic acid construct;
and
A method of treatment for a cardiac disease or a cardiac defect, comprising administering the AAV2 vector particle according to claim 1 (as described in (1) above) to a patient who is diagnosed as having the cardiac disease or cardiac defect,
wherein the nucleic acid construct comprises an expression cassette encoding an effector molecule,
wherein the cardiac disease or cardiac defect is pathological cardiac hypertrophy, and
wherein the effector molecule is long noncoding RNA (lncRNA) H19;
does not reasonably provide enablement for:
An AAV2 viral vector particle comprising any nucleic acid construct for any effector molecule, comprising any capsid protein (CAP) which C-terminally to amino acid NO. 587 of the wild-type amino acid sequence of CAP of SEQ ID NO: 56 contains an inserted amino acid section comprising SEQ ID NO: 1, wherein the inserted amino acid section does not comprise an N-linker AAA or ASA amino acid sequence and a C-linker AA amino acid sequence flanking the sequence of SEQ ID NO: 1, and wherein the AAV2 viral vector particle is for any use;
A process for producing AAV2 viral vector particles by delivery of any components for AAV vector production in any cultivated eukaryotic cell, followed by cell lysis and removal of cellular components and plasmid DNA, and further purification of AAV viral vector particles, wherein the AAV2 viral vector particles comprises any CAP which C-terminally to amino acid NO. 587 of the wild-type amino acid sequence of CAP contains an inserted amino acid section comprising SEQ ID NO: 1, wherein the inserted amino acid section does not comprise a 3x alanine N-linker and a 2x alanine C-linker flanking the sequence of SEQ ID NO: 1, and wherein the AAV2 viral vector particle is for any use; nor
A method of treatment for any cardiac disease, including cardiac defects, comprising administering the AAV2 vector particle according to claim 1 to any patient who is diagnosed as having the cardiac disease or cardiac defect, wherein the nucleic acid construct comprises any sequence encoding any effector molecule;
is maintained. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended independent claim 1 to address some of the issues of indefiniteness identified in the prior action. However, the amendments do not address any of the issues identified in the scope of enablement rejection under U.S. 35 112(a) presented in the prior action.
Applicant argues that:
claims 12 and 13 depend upon claim 1 and therefore are not independent claims;
claim 1 is a product claim and no language for treating a cardiac disease appears in claim 1 such that product claim 1 is unconstrained by methods of treatment;
claim 1 is a product claim which has no language regarding a manufacturing method such that claim 1 is unconstrained manufacturing methods;
claim 1 recites specific sequences for the capsid protein and is not directed to any capsid protein and any nucleic acid;
the Office Action does not clearly state as to why SEQ ID NO: 1 should be further limited to include an N-terminal and a C-terminal linker, and there is no basis in Section 112(a) for the requirement of limiting the CAP as comprising linker sequences at both ends of the inserted amino acid sequence in that the insertion sites 587, 588, and 453 expose an inserted amino acid sequence and there is no evidence that the further exposing of insert by the linkers is absolutely necessary;
Applicant does not agree that section 112(a) requires them to restrict the claimed AAV2 viral vector particle to wherein the effector molecule is long noncoding RNA H19 because the encoded effector molecule shall not limit the scope of claim 1 by sequences of the effector molecules in that the effector molecule is encoded in the ssDNA packaged in the CAP of AAV2 and does not affect its packaging nor the specificity for cardiomyocytes; and
because the manufacturing method of claim 12 and treatment of claim 13 both depend on claim 1, the alleged enablement issues 2 through 3 or 4 even if they are considered in connection with claims 12 (issue 2) or claim 13 (issues 3 and/or 4) have been also addressed.
However, this is not agreed.
Regarding Applicant’s argument 1), note that although previously presented claim 13 encompasses amended independent claim 1, claim 12 has no reference to any other claim and as such neither depends upon nor encompasses amended independent claim 1.
Regarding Applicant’s arguments 2), note that the enablement rejection is not merely a rejection of independent claim 1 but addresses the issues applicable to all the recited claims. Nor are products exempt from meeting the enablement requirement. “Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention. The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S. 261, 270 (1916) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied. See also In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does not use the term "undue experimentation," it has been interpreted to require that the claimed invention be enabled so that any person skilled in the art can make and use the invention without undue experimentation.” [MPEP 2164.01]. “With respect to the breadth of a claim, the relevant concern is whether the scope of enablement provided to one skilled in the art by the disclosure is commensurate with the scope of protection sought by the claims.” [MPEP 2164.08].” “When analyzing the enabled scope of a claim, the teachings of the specification must not be ignored because claims are to be given their broadest reasonable interpretation that is consistent with the specification. ‘That claims are interpreted in light of the specification does not mean that everything in the specification must be read into the claims.’" [MPEP2164.08].
The dependent claims recite intended uses of the claimed AAV2 viral vector according to claim 1 for treating a disease or defect of cardiac myocytes or for treating a disease or defect of muscular myocytes or of skeletal muscle cells [claim 6] and for treating a cardiac disease, including cardiac defects [claim 13]. Additionally, the specification teaches that the intended use of the AAV2 viral vector recited in claim 1 is “for use in gene therapy, especially for use in the treatment of cardiac diseases including cardiac defects, e.g., for use in the genetic treatment of cardiac diseases including cardiac defects” [pg 1 ¶ 1]. Thus, consideration of issues of enablement in light of specification requires considering the enablement of the AAV2 viral vector particle product recited in claim 1 in view of the intended use of the AAV2 viral vector particle as taught in the dependent claims and the specification, wherein the AAV3 viral vector particle is intended for use in the genetic treatment of cardiac diseases including cardiac defects.
Regarding Applicant’s argument 3), Applicant seems to be confusing the three enabled inventions and three unenabled inventions with the four issues of enablement identified and discussed in the prior action. The list of three enabled/unenabled inventions separates out the scopes of the three inventions- the AAV2 particle product, the method of making the AAV2 particle product, and the method of using the AAV2 product to treat cardiac disease. As such, the discussion of enablement issues specifically directed toward the method of making the AAV2 viral vector particles, as recited in claim 12, are directed to the scope of enablement identified for the method of making as recited in claim 12. The prior rejection does not include specific details of a method of making for the enabled product scope.
Regarding Applicant’s argument 4), Applicant is drawing excerpt from the unenabled scope rather than addressing the issues identified as contributing to the scope of enablement. The unenabled scope of the prior rejection states:
“An AAV2 viral vector particle comprising any nucleic acid construct for any effector molecule, comprising any capsid protein (CAP) which C-terminally to amino acid NO. 587 of the wild-type amino acid sequence of CAP of SEQ ID NO: 56 contains an inserted amino acid section comprising SEQ ID NO: 1, wherein the inserted amino acid section does not comprise an N-linker AAA or ASA amino acid sequence and a C-linker AA amino acid sequence flanking the sequence of SEQ ID NO: 1, and wherein the AAV2 viral vector particle is for any use” [page 10 ¶ 2].
As such, the scope of enablement rejection as presented in the prior action does not allege that claim 1 is directed to “any capsid protein” without limitation.
Regarding Applicant’s argument 5), note that the prior action specifically recites, “The disclosure teaches the screening and identification of AAV2 viral vectors comprising inserted amino acid sections comprising a 7-amino acid variable sequence flanked by N-terminal AAA or ASA amino acid residues and C-terminal AA amino acid residues, wherein the 7-amino acid sequence of SEQ ID NO: 1 was identified to have beneficial activity with regards to level of infectivity, antibody reactivity, and tropism [page 7 ¶ 5, Figure 1-6]. The specification does not teach the insertion of SEQ ID NO: 1 in the absence of the indicated N-linker and C-linkers sequences nor in the presence of any other N-linker or C-linker sequences.” [page 12 ¶ 3]. Further, Lee was cited for teaching the unpredictability of mutating AAV capsid proteins to improve transduction efficiency, provide for specific tissue targeting, and/or to prevent recognition by the host immune system. Therefore, given the art recognized unpredictability in achieving outcomes such as specific tissue targeting, and the lack of disclosures in the specification for any inserts achieving the desired tissue targeting in the absence of the limited linker constructs disclosed in the specification, an ordinarily skilled artisan at the time of filing would have considered achieving the specific tissues targeting therapeutic benefits in the absence of the specific construct disclosed, including the disclosed linkers, as highly unpredictable.
Regarding Applicant’s argument 6), note that the coding sequence of the encoded effector molecule is a structural component of independent claim 1. Claim 1 is not directly merely to a capsid protein or to an empty viral particle wherein the encoded sequence would only be relevant to the packaging of the viral particle.
Additionally, as discussed above, enablement of claim 1 is considered in light of the intended use disclosed in the specification and the dependent claims. Note additionally, as discussed in the prior action, Applicant has not demonstrated an enabled use of any other effector molecule for the intended use as recited in the specification and in the dependent claims.
As discussed in the prior action, although the specification also teaches the expression of eGFP, eGFP is merely a fluorescent protein used as a marker for viral transduction with no beneficial functions for the treatment of any cardiac disease or any cardiac disorder [page 15 ¶ 4, Figure 6]. As further discussed in the prior action, the art at the time of filing teaches that gene therapy requires the delivery/ targeting of specific genes relevant to the specific disease or disorder being treated [Dunbar et al. 2018, Science, 359 (175), 1-10, Table 2]. Accordingly, expression of eGFP as a marker for viral transduction is not indicative that expression of any effector molecule can be used in the genetic treatment of cardiac diseases including cardiac defects.
Regarding Applicant’s argument 7), note that even wherein a product is enabled, it does not necessarily follow that a method of making the product nor a method of using that product would necessarily be enabled. As discussed above, none of the AAV2 product, the method of making the AAV3 product, nor the method of using the AAV2 product for treating a cardiac disease or defect are enabled to the full scope of the claims as written. Applicant has not amended the claims to align with the identified enabled scope. Applicant’s mere assertion that the method of making the product and the method of treating using the product are enabled because considerations relevant to making and using are not thought by Applicant to be relevant to the product itself is not a meaningful argument for asserting the enablement of the claimed method of making nor the claimed method of using.
Therefore, Applicant’s arguments do not overcome the scope of enablement rejection under 35 U.S.C. 112(a), and the rejection is maintained.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the 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 Dr. KATIE L PENNINGTON whose telephone number is (703)756-4622. The examiner can normally be reached M-Th 8:30 am - 5:30 pm, Friday 8:30 am - 12:30 pm CT.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634
