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
This Office Action is a response to Applicant’s Election filed May 11, 2026.
Claims 3, 5, 7-11, 13-15, 21, 23, 25, 30, 35, 37, 40, 43, and 46-48 are pending in the instant application.
Election/Restrictions
Applicant’s election (without traverse) of Group II in the reply filed on May 11, 2026 is acknowledged. The further species election of capsid protein, SEQ ID NO:1 and the SERCA2a (SEQ ID NO:29) transgene in the reply filed on May 11, 2026 is also acknowledged.
Claims 3, 5, 7-11, 13, 14, 30, 35, 37, 47 and 48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 11, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 15, 21, 23, 25, 40, 43, and 46 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed December 30, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed May 23, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
The listing of references in the specification at pages 67-73 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.
Priority
Acknowledgment is made of Applicant's claim for foreign priority based on EU 21171861.4, filed May 3, 2021 and EU 20217171.6, filed December 23, 2020. The certified copies have been placed in the file.
Drawings
The Drawings filed on June 23, 2023 are acknowledged. However, the Drawings are objected to because some Drawings reference the colors “blue”, “purple”, "red" and "green". See Figure 1C, for example. In the instant application, color drawings have been filed without an accompanying petition. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), three sets of color drawings or color photographs, as appropriate, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37CFR 1.84(b)(2). Note that the requirement for three sets of color drawings under 37 CFR 1.84(a)(2)(ii) is not applicable to color drawings submitted via EFS-Web. Therefore, only one set of such color drawings is necessary when filing via EFS-Web.
Nucleotide Sequence Disclosures
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. §1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §1.821-1.825 for the reason(s) set forth below or on the attached Notice To Comply with Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures. The disclosure contains sequences which fall under the purview of 37 CFR 1.821 through 1.825 as requiring SEQ ID NOs., but which are not so identified. For example, see page 57. This is an example and does not indicate that the Examiner has made an exhaustive review of the application. Applicant must fully comply with the sequence rules for any response to this action to be considered fully responsive.
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 21, 43 and 46 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 pre-AIA the applicant regards as the invention.
The claims are indefinite because the term, “preferably” creates ambiguity regarding whether the listed feature is an essential limitation or an optional one. The term does not define the invention's boundaries and therefore renders the claims indefinite. 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 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 pre-AIA 35 U.S.C. 103(a) 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 15, 21, 23, 25, 40 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019/199867 A1 in view of WO 2019/028306 A2 (both references submitted and made of record on the IDS filed May 23, 2025).
The claims are drawn to a recombinant viral vector, wherein the vector comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein comprising (a) the amino acid sequence of SEQ ID NO:1; (b) the amino acid sequence of SEQ ID NO:2; (c) the amino acid sequence of SEQ ID NO:3; (d) a variant of (a), (b) or (c) which differs from the sequence of SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3 by the modification of one amino acid; (e) the amino acid sequence of SEQ ID NO:24; (f) the amino acid sequence of SEQ ID NO:25; (g) the amino acid sequence of SEQ ID NO:26; (h) the amino acid sequence of SEQ ID NO:27; (i) a variant of (e), (f), (g) or (h) which differs from the sequence of SEQ ID NO:24,SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27 by the modification of one amino acid, (j) the amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; or (k) an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; for use (A) in a method of treating or preventing a heart disease in a primate, wherein said method of treating or preventing a heart disease comprises the transduction of primate cardiomyocytes; or (B) in a method of treating or preventing cardiomyopathy in a primate; or (C) in a method of treating or preventing heart failure or chronic heart failure in a primate. It is noted that in the election filed on May 11, Applicants elected the capsid protein, SEQ ID NO:1.
Regarding claims 15 and 43, WO 2019/199867 teach AAV-BR1 is an AAV2 variant displaying the NRGTEWD (SEQ ID NO:53) epitope that was isolated during in vivo screening of a random AAV display peptide library. AAV-BR1 shows high specificity accompanied by high transgene expression in the brain and spinal cord with minimal off-target affinity (including for the liver) as evidenced by Körbelin et al., EMBO Mol Med. 2016; 8(6): 605-609 (submitted and made of record on the IDS filed May 23, 2025). NOTE: NRGTEWD (SEQ ID NO:53) of WO 2019/199867 comprises SEQ ID NO:1 of the present invention. Also see the evidence of WO 2015/158749 who teaches AAV-BR1 shows high specificity accompanied by high transgene expression in the brain and spinal cord with minimal off-target affinity (including for the liver).
WO 2019/199867 also teaches the AAV of their invention are administered intravenously.
Concerning the “for use” language recited in claim 15, Applicant should note that that the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the recombinant viral vector, wherein the vector comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein comprising the amino acid sequence of SEQ ID NO:1 of the present invention as taught and suggested by WO 2019/199867 is capable of use in (A) a method of treating or preventing a heart disease in a primate, wherein said method of treating or preventing a heart disease comprises the transduction of primate cardiomyocytes; or (B) in a method of treating or preventing cardiomyopathy in a primate; or (C) in a method of treating or preventing heart failure or chronic heart failure in a primate, and therefore meets the functionality reported in the present claim, absent some evidence to the contrary.
Regarding claim 21, WO 2019/199867 teach the adenovirus may be of any of the different known serotypes, including AAV-2.
Considering claim 23, WO 2019/199867 teach one strand of each nucleic acid sequence is shown, but the complementary strand is understood as included in embodiments where it would be appropriate.
Regarding claim 25, WO 2019/199867 does not teach the transgene of their invention is SERCA2a.
WO 2019/028306 teaches the use of a transgene encoding the therapeutic gene, SERCA2a. The SERCA2a transgene of WO 2019/028306 comprises SEQ ID NO:29 of the present invention. See Table 5 of WO 2019/028306, SEQ ID NO: 1803, GenBank Accession No. NP_001672.1.
Before the effective filing date of the claimed invention, an adeno-associated viral particle (AAV) comprising a capsid protein and a transgene were known in the prior art. Before the effective filing date of the claimed invention, it was well-known that the AAVs deliver transgenes to cells and tissues.
Starting from WO 2019/199867, it would have been obvious for a person of ordinary skill in the art to devise a recombinant viral vector, wherein the vector comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein comprising (a) the amino acid sequence of SEQ ID NO:1 as presently claimed.
A person of ordinary skill in the art would have been motivated to modify the teachings of WO 2019/199867 to include the SERCA2a transgene of WO 2019/028306 for the purpose of expressing the therapeutic gene in cells and tissues.
Therefore, the subject matter of claims 15, 21, 23, 25, 40 and 43 is obvious over WO 2019/199867 in view of WO 2019/028306.
******
Claims 15, 21, 23, 25, 40, 43, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Körbelin et al., EMBO Mol Med. 2016; 8(6): 605-609 (submitted and made of record on the IDS filed May 23, 2025).
The claims are as described above.
Regarding claims 15 and 43, Körbelin et al. teach AAV-BR1 is an AAV2 variant displaying the NRGTEWD epitope that was isolated during in vivo screening of a random AAV display peptide library. AAV-BR1 shows high specificity accompanied by high transgene expression in the brain and spinal cord with minimal off-target affinity (including for the liver). NOTE: NRGTEWD of Körbelin et al. comprises SEQ ID NO:1 of the present invention. Also see the evidence of WO 2015/158749 who teaches AAV-BR1 shows high specificity accompanied by high transgene expression in the brain and spinal cord with minimal off-target affinity (including for the liver).
Körbelin et al. also teaches the AAV of their invention are administered intravenously. See Figure EV5, for example.
Concerning the “for use” language recited in claim 15, Applicant should note that that the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the recombinant viral vector, wherein the vector comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein comprising the amino acid sequence of SEQ ID NO:1 as taught and suggested by Körbelin et al. is capable of use in (A) a method of treating or preventing a heart disease in a primate, wherein said method of treating or preventing a heart disease comprises the transduction of primate cardiomyocytes; or (B) in a method of treating or preventing cardiomyopathy in a primate; or (C) in a method of treating or preventing heart failure or chronic heart failure in a primate, and therefore meets the functionality reported in the present claim, absent some evidence to the contrary.
Regarding claim 21, Körbelin et al. teach the adenovirus may be of any of the different known serotypes, including AAV-2.
Considering claim 23, Körbelin et al. the transgenes used in their study are ssDNA or dsDNA.
Regarding claim 46, Körbelin et al. teach heart cells were transduced with the AAV-BR1 used in their studies. See Figure 4.
Regarding claim 25, Körbelin et al. does not teach the transgene of their invention is SERCA2a.
WO 2019/028306 teaches the use of a transgene encoding the therapeutic gene, SERCA2a. The SERCA2a transgene of WO 2019/028306 comprises SEQ ID NO:29 of the present invention. See Table 5 of WO 2019/028306, SEQ ID NO: 1803, GenBank Accession No. NP_001672.1.
Before the effective filing date of the claimed invention, an adeno-associated viral particle (AAV) comprising a capsid protein and a transgene were known in the prior art. Before the effective filing date of the claimed invention, it was well-known that the AAVs deliver transgenes to cells and tissues.
Starting from Körbelin et al., it would have been obvious for a person of ordinary skill in the art to devise a recombinant viral vector, wherein the vector comprises a capsid and a transgene packaged therein, wherein the capsid comprises at least one capsid protein comprising (a) the amino acid sequence of SEQ ID NO:1 as presently claimed.
A person of ordinary skill in the art would have been motivated to modify the teachings of Körbelin et al. to include the SERCA2a transgene of WO 2019/028306 for the purpose of expressing the therapeutic gene in cells and tissues.
Therefore, the subject matter of claims 15, 21, 23, 25, 40, 43 and 46 is obvious over Körbelin et al. in view of WO 2019/028306.
Improper Markush Groups
Claims 15, 25 and 40 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Regarding claim 15, the Markush grouping of capsid proteins selected from the group consisting of (a) the amino acid sequence of SEQ ID NO:1; (b) the amino acid sequence of SEQ ID NO:2; (c) the amino acid sequence of SEQ ID NO:3; (d) a variant of (a), (b) or (c) which differs from the sequence of SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3 by the modification of one amino acid; (e) the amino acid sequence of SEQ ID NO:24; (f) the amino acid sequence of SEQ ID NO:25; (g) the amino acid sequence of SEQ ID NO:26; (h) the amino acid sequence of SEQ ID NO:27; (i) a variant of (e), (f), (g) or (h) which differs from the sequence of SEQ ID NO:24,SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27 by the modification of one amino acid, (j) the amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; or (k) an amino acid sequence having at least 90% identity to the amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: The groupings do not share a single structural similarity. Between these different capsid proteins, they do not share a single structural similarity as they are encoded by different amino acid sequences. See respective sequences associated with each capsid protein sequence identifier (SEQ ID NO.). Also, see the present Specification for description of each unique sequence at pages 47 and 48.
Regarding claim 25, the Markush grouping in the claim is improper because the alternatives defined by the Markush grouping do not share a single structural similarity and a common use flowing from the shared structural similarity. For example, the transgenes as claimed are entirely different genes (e.g. huMydgf; SERCA2a, SUMO1; S100A1; VEGF; or a microRNA involved in the regulation of the MAPK pathway; the MYOD pathway; the FOXO3 pathway; or the ERK-MAPK pathway). The transgenes of claim 25 do not share a single structural similarity and a common use that flows from the structural similarity feature.
Regarding claim 40, the Markush grouping in the claim is improper because the alternatives defined by the Markush grouping do not share a single structural similarity and a common use flowing from the shared structural similarity. For example, the SERCA2a transgenes as claimed are entirely different proteins comprised of entirely different amino acids. The SERCA2a transgenes of claim 40 do not share a single structural similarity and a common use that flows from the structural similarity feature. See respective sequences associated with each SERCA2a transgene sequence identifier (SEQ ID NO.). Also, see the present Specification for description of unique SERCA2a transgene sequences at page 48.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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