DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-8 are pending in this application.
This application is a divisional of US Patent Appl No.: 16/754,659, filed 04/08/2020 (now U.S. 11,485,967) which application is a 371 filing of PCT/US2018/054982 filed 10/9/2018 which claims priority to provisional application 62/570,508, filed 10/10/2017, and 62/633,412, filed 02/21/2018.
The instant claimed subject matter was submitted with the claims of the PCT filing and therefore the effective filing date of the claims is 10/9/2018.
Information Disclosure Statement
Information disclosure statements filed 11/24/2025, 3/28/2025, 11/6/2024, 4/20/2023 and 11/17/2022 have been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action. The documents listed as Search Reports and communications have been considered but have been crossed off the 1449 so that it will not appear on the face of any patent issuing from the instant application.
Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 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. Specifically, figures 9 and 15 contain sequences that are not identified by sequence identifier numbers. If the sequences can be found in the sequence listing it would be remedial to insert the appropriate SEQ ID NO:s. If not, a substitute paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, CRF and letter stating that the contents of the sequence listing and the CRF are the same and contain no new matter is required.
Specifically, the letter stating that the contents of the sequence listing and the CRF are the same must state that there is no new matter by the submission of the sequence listing and CRF. A substitute paper copy of the “Sequence Listing”, as well as an amendment directing its entry into the specification, CRF and letter stating that the contents of the sequence listing and the CRF are the same and contain no new matter is required.
Drawings
Figure 9 is objected to under 37 CFR 1.83(a) because it fails to show any details as described in the specification. Specifically, figure 9 is cut off on the right end and is missing some of the text. Any structural detail that is essential for a proper understanding of the disclosed invention should be shown in the drawing. MPEP § 608.02(d). A proposed drawing correction or corrected drawings are required in reply to the Office action to avoid abandonment of the application. The objection to the drawings will not be held in abeyance.
Objections to the Specification
In ¶0016, the verb “is” is missing in the phrase “In a further aspect of the inventive subject matter, the inventors also contemplate method of producing a plurality of recombinant therapeutic viruses that includes a step of providing a host cell that genetically engineered to conditionally expresses an entity that reduces expression of a viral payload gene in the host cell”. This is true of ¶0018).
In ¶0021, grammatically it should be –Contemplated genetically engineered cells may--.
As well, ¶0057 has a grammatical error in line 6 of the paragraph. It should say –at a target titer of at least--.
Claim Objections
Claims 1 and 7 are objected to because of the following informalities: in claim 1, line 1, the phrasing “an mRNA for a recombinant payload” doesn’t have the same meaning as intended. The mRNA is not for a payload but –encoding for a recombinant payload--.
Grammatically, claim 7 should recite –encodes—instead of “encoding”. Appropriate correction is required.
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.
Claim 4 recites the limitation "the binding site" in claim 1. There is insufficient antecedent basis for this limitation in the claim. While claim 1 recites there is at least one binding site, the reference does not indicate if the claim is referring to just one of the at least one or all of the at least one binding sites.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn a virus that quite broadly encodes any recombinant payload. The claim specifies that the sequences encode an mRNA but any sequence whether RNA or DNA that encodes a protein will encode the mRNA. The RNA as claimed also comprises a 3’UTR comprising an shRNA binding site. Regarding the instant invention, the disclosure teaches construction of a test gene with a 3’ UTR site and a shRNA coding sequence. The targets were down-regulated. As to use, the disclosure teaches that the goal of the vector design is to increase titer and reduce expression of a viral payload gene in a host cell. One potential method is suppressing expression of a recombinant protein therein by including a binding site in the 3’ UTR (see ¶0014). This is creating a vector with conditional expression (see e.g. ¶0016). Discussion of the design is provided in terms of developing virus that do not express the payload in host cells provided for producing the virus as this can place and damper on production effects but the host cell (see e.g. ¶0051). Thereafter, the payload is expressed in cells wherein the expression is desired. “Entities” (shRNA inclusive) that are naturally present in a cell or genetically engineered to be expressed in a cell. The binding site are naturally present or engineered to be present in the mRNA of the payload (see e.g. ¶0052-0053). The goal is
[0057] Regardless of the manner of suppressing expression of the payload of the recombinant virus, it is contemplated that suitable systems will afford a significantly improved uniformity in terms of yield and/or production time required to reach a predetermined quantity of therapeutic viral particles irrespective of the content and/or size of the payload.
This is as related to the claims is depicted in figure 12 and described starting in ¶0065).
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In test cells, applicants demonstrated that they could downregulate expression of the “cargo”.
While the general use is described in the disclosure,
As will be appreciated, by housing these complementary target sequences in the 3'UTR of transgenes carried in the AdV5 genome, emerging transcripts are degraded thereby preventing any toxic effects of the would-be gene products. Most preferably, the shRNAs will be selected such that they do not recognize endogenous genes in the production cells. Moreover, it is further contemplated that recombinant constructs/host cells can be generated that express multiple (e.g., at least two, or at least three) different shRNAs along with the 3'UTRs that carry target sites for each of those shRNAs to so enhance the silencing potential.
And host cells while generically referenced are described in terms of producer cells only. First, the only references when applied to host cells is to CHO, HEK293 and EC7 as producer cells (see e.g. ¶0012, 0015, 0047, 0073). Hence, the reference to patient cells is missing from the disclosure.
Secondly, shRNA are generically referenced in the disclosure as tool to regulate expression. However, most specifically, the claims require an shRNA binding site absent in a patient cell. This requires knowing who the patient is, what cell is being referenced and then identification of the shRNA binding site. Furthermore, as the claims define the shRNA binding site as one that is absent in a patient cell to which the virus is administered. This complicates the nature of the claims as the claims are drawn to a product, the virus, and as the virus is not disinterred to patient one cannot know what the patient is or what the cell is. Applicants have not described any of these components. The claims lack adequate description to link structure to these required functions. The Court indicated that while applicants are not required to disclose every species encompassed by a genus, the description of a genus is achieved by the recitation of a precise definition of a representative number of members of the genus, such as by reciting the structure. Structural features that could distinguish the compounds of the claimed genus from others not encompassed by the genus are missing from the disclosure. In this case, there are specific elements referenced but the claims reference these structures with broad generic functional terms that represent a large and diverse genus of elements.
Closest prior art
Jain et al teach vectors comprising toxic “payloads” that are modified by having miRNA sites in their 3’ UTR. The sites are selectively repressed based upon the cell type. Specifically, miR122 is repressed in hepatocellular carcinoma (see page 288, col 2). However, there is no indication that such regulation by shRNA would have bene possible as the art does not teach shRNA binding sites that are not present in patient cells.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIA MARVICH whose telephone number is (571)272-0774. The examiner can normally be reached on 8 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Maria Leavitt can be reached on 571-272-1085. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARIA MARVICH/Primary Examiner, Art Unit 1633
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