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
Claims 3, 15, and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (claim 15) or nonelected species (claims 3, and 15- see Applicant’s response to restriction, page 2), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/19/2026.
Applicant’s election of Group 1 (vector) and Cumate-CuO regulable system (repressible operon), CMV (promoter), and CASP2 (gene of interest- also reads on a gene of interest with cytotoxicity to cells for lentiviral packaging, apoptotic gene and cell cycle-associated gene in claims 7-9- see pg. 2 of Applicant’s Remarks) in the reply filed on 3/19/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-16 are pending.
Claims 1, 2, and 4-14 are pending and under examination.
Priority
This application claims priority to CN202011418514.0 filed 12/07/2020 and PCT/CN2021/135790 filed 12/06/2021.
The Examiner notes that should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Additionally, the Examiner notes that Applicant cannot rely upon the certified copy of the foreign priority application to overcome a rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
As such, the effective filing date of the instant claims is 06/07/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/07/2023 is considered by the examiner.
Drawings
The drawings are objected to because Figures 1-5, 7, 11, 13, 15, 18-25, and 27-30 are too small/blurry to read. 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.
Specification
The specification filed 06/07/2023 is accepted.
Claim Rejections - 35 USC § 112(a) – Written Description
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1, 2, and 4-14 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “wherein the first long terminal repeat is positioned upstream of the reversely inserted gene expression cassette in a direction of viral genome expression,
the second long terminal repeat is positioned downstream of the reversely inserted gene expression cassette in a direction of viral genome expression”.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The disclosure of a single species is rarely, if ever, sufficient to describe a broad genus, particularly when the specification fails to describe the features of that genus, even in passing. (see In re Shokal 113USPQ283(CCPA1957); Purdue Pharma L.P. vs Faulding Inc. 56 USPQ2nd 1481 (CAFC 2000).
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997).
The phrase “reversely inserted gene expression cassette” has not been properly described in the disclosure. The specification offers little guidance on this recitation. A search of “reverse” in the specification only returned reiterations of the claim language and the following from [0033]: “Figure 31 shows schematic diagrams of A) lentiviral packaging with a reverse expression cassette encoding no repressible operon, B) lentiviral packaging with a reverse expression cassette encoding a tryptophan operon, and C) lentiviral packaging with a reverse expression cassette encoding a Cumate-CuO regulable system.” Additionally, the end of each example recites “The principle can refer to the illustration in Figure 31” (e.g., [0119]), which does not provide any further guidance for an artisan.
From the disclosure, an artisan cannot discern what a “reversely inserted gene expression cassette” is. For example, is the “reverse expression cassette” the same as the “reversely inserted gene expression cassette” recited in the claims? How are these expression cassettes in reverse? The reverse expression cassettes of Figure 31 are not reversely oriented, as 5’ is upstream and 3’ is downstream of the expression cassette, as an artisan would expect.
Further, the specification does not describe how the reversed expression cassette would function if the cassette is not read in the 5’ to 3’ direction, or what the purpose for this orientation is. A search of the art did not return results for a functioning expression cassette that is translated 3’ to 5’.
Thus, in light of the lack of guidance in the specification and the art on a “reversely inserted gene expression cassette”, the artisan would not have understood the Applicant to have been in possession of the invention as claimed.
Claim 1 recites “the repressible operon is capable of repressing expression of the gene of interest downstream of the repressible operon in the presence of a repressor.”
Claim 6 recites “the repressible operon exerts a negative effect on viral packaging in the case where the gene of interest is expressed.”
Claim 7 recites “wherein the gene of interest has cytotoxicity to cells for lentiviral packaging.”
Claim 10 recites “wherein the gene of interest directly inhibits replication and/or assembly of virus.”
Claim 13 recites “wherein the lentiviral vector packaging system is capable of producing HIV vector particles having only primary infectivity and no replication capacity.”
Either these are inherent properties of (that naturally flows from) the structure of claim 1, or they are not.
The claim denotes that not all of the structures/method steps of the independent claim are able to achieve the functional property(ies) recited in the dependent claim(s).
To the extent it is not an inherent property (that naturally flows) from the product/method of the independent claim, then something must change. The claim is considered to lack adequate written description for failing to recite the structure that is necessary and sufficient to cause the repressible operon, gene of interest, and vector to possess these characteristics. The claim limitations recited above merely state functional characteristics without providing any indication about how the characteristic is provided. The characteristic does not follow from (is not an inherent property of) the structure recited in the claim, so it is unclear whether the claim requires some other structure to be added to the composition to provide the characteristic.
The specification fails to disclose what structural changes to the composition is/are necessary and sufficient to cause the recited function of being capable of repressing expression of the gene of interest downstream of the repressible operon in the presence of a repressor, for example, and thus the ordinary artisan would not know what modification(s) must be made in order to fulfill the instant recitation. For example, how would an artisan know what changes to the repressible operon results in the operon being capable of repressing expression of the gene of interest downstream of the repressible operon in the presence of a repressor? Or what changes to the repressible operon result in the operon exerting a negative effect on viral packaging in the case where the gene of interest is expressed, versus a repressible operon that does not exert a negative effect on viral packaging in the case where the gene of interest is expressed?
The claims fail to recite, and the specification fails to disclose what modification(s) to a lentiviral vector packaging system that is uncapable of producing HIV vector particles having only primary infectivity and no replication capacity, transforms said lentiviral vector packaging system into one that is now necessarily and predictably capable of producing HIV vector particles having only primary infectivity and no replication capacity, for example.
Without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Stanford (US20210024924A1, published 01/28/2021; originally filed 03/04/2020) is considered relevant prior art for teaching a vector comprising a 5’ long terminal repeat (LTR), gene expression cassette comprising a repressible operon and promoter, and a 3’ LTR (i.e., the same structure recited in base claim 1). However, Stanford is silent on the functionality of the vector (as part of a packaging system) being capable of producing HIV particles having only primary infectivity and no replication capacity, and does not provide any further guidance on what structure of the vector would cause this functionality. Instead, the functionality of the vector(s) for genetic engineering to treat diseases such as Huntington’s Disease (e.g., when targeting CASP2) [0281] are instead described.
Liu (www.genscript.com/learning-center/lentivirus-the-ultimate-answer-for-efficient-gene-delivery.html; published 04/21/2025) is considered relevant art for providing an overview of lentiviruses. Liu teaches that lentiviruses are derived from HIV-1, and that through genetic engineering, regulatory and auxiliary genes necessary required for viral replication are removed, and heterologous elements are introduced to create a replication-deficient recombinant vector system.
Liu does not provide further guidance on how an artisan would possess a vector for lentiviral packaging comprising LTRs and a gene expression cassette/a lentiviral vector packaging system comprising said vector that would also produce HIV vector particles with replication capacity. Instead, Liu teaches that it is known in the art that lentiviruses do not have replication capacity.
Thus, for the reasons outlined above, it is concluded that the claims do not meet the requirements for written description under 35 U.S.C. 112, first paragraph, and the Artisan would not have understood Applicant to have been in possession of the invention as claimed.
Claim Rejections - 35 USC § 112(b)
Claims 1, 2, and 4-14 is/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.
Claim 1 recites “the reversely inserted gene expression cassette”. It is unclear what “reversely inserted” means, as every example of the disclosure shows the cassette being read in the correct direction (i.e., 5’ to 3’).
A search of “reverse” in the specification does not return a clear definition for the phrase. [0033] recites “Figure 31 shows schematic diagrams of A) lentiviral packaging with a reverse expression cassette encoding no repressible operon, B) lentiviral packaging with a reverse expression cassette encoding a tryptophan operon, and C) lentiviral packaging with a reverse expression cassette encoding a Cumate-CuO regulable system.” It is unclear if this “reverse expression cassette” is the same as the “reversely inserted gene expression cassette” recited in the claims. Additionally, it is unclear how Figure 31 depicts a reverse expression cassette, as it appears that the strand would be translated 5’ to 3’.
For prior art consideration, the gene expression cassette in the claimed vector is interpreted to be forwardly inserted based on the examples of the disclosure.
Claim 6 recites “wherein a gene of interest is inserted downstream of the repressible operon, and the repressible operon exerts a negative effect on viral packaging in the case where the gene of interest is expressed.”
There is insufficient antecedent basis for this limitation in the claim, as it is unclear whether the gene of interest recited in claim 6 is referring to the same optional gene of interest recited in base claim 1. If not, is the gene of interest of claim 6 part of the same gene expression cassette? Can multiple gene of interests be present in the vector? It would be remedial to change “a gene of interest” to “the gene of interest” in lines 1-2 of claim 6 if claim 6 is referring to the same optional gene of interest recited in claim 1. For examination purposes, the gene of interest recited in claim 6 may be the same or a different gene than the one recited in claim 1.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 5, 6, and 12-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Stanford (US20210024924A1, published 01/28/2021; originally filed 03/04/2020).
Regarding claim 1, Stanford discloses a lentiviral plasmid that is integrated into HEK 293T cells to generate a reporter cell line, HEK293T QMS (CMVS-CuO luc-p2A-GFP, EF1alpha-cymR). This disclosure reads on the claim language of instant claim 1 (a vector for lentivirus comprising a first long terminal repeat (LTR), a gene expression cassette comprising a repressible operon and promoter, and a second long terminal repeat, wherein the first LTR is upstream (5’) of the expression cassette, and the second LTR is downstream of the expression cassette) [0129] (Fig. 10- included below).
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Regarding claim 2, Stanford discloses the repressible operon being a Cumate-CuO regulable system (Fig. 10).
Regarding claim 5, Stanford discloses the promoter being CMV (Fig. 10).
Regarding claims 6 and 13, as discussed in the 112(a) written description rejection above, these are functional properties that do not further limit the structure of the claimed vector. As such, absent evidence to the contrary, the structure disclosed by Stanford would inherently be able to carry out functions such as exerting a negative effect on viral packaging and being capable of producing HIV vector particles having only primary infectivity and no replication capacity.
Regarding claim 12, the vector disclosed by Stanford further comprises an enhancer (e.g., WPRE) (Fig. 10).
Regarding claim 14, Stanford discloses the lentiviral vector packaging system being a three-plasmid packaging system, e.g., [0374-0377], [0397-0398].
Claim Rejections - 35 USC § 102/103
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.
Claim(s) 7-10 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Stanford (US20210024924A1, published 01/28/2021; originally filed 03/04/2020).
As shown above, the base claims are obvious over Stanford.
The vector disclosed by Stanford above (Fig. 10) comprises GFP as a gene of interest. However, Stanford discloses that the gene of interest in a vector may be a gene associated with neoplasia, such as those in the caspase family, including CASP2 [0280].
It would have been obvious to one of ordinary skill in the art to substitute CASP2 for luciferase/GFP as the gene of interest in the vector disclosed by Stanford and arrive at the claimed invention. One would have a reasonable expectation of success because Stanford suggestions such modification, and it is routine in the art to substitute the gene present in a gene expression cassette depending on the motivation of the artisan. An artisan would be motivated to make this substitution because as taught by Stanford, the CASP2 gene is associated with cellular performance, and the disclosed editing system may be used to treat diseases associated with cellular condition, such as those associated with disrupted CASP2 (Stanford notes that CASP2 is specifically associated with Huntington’s Diseases signaling, apoptosis signaling, death receptor signaling) [0281].
Additionally, regarding claims 7 and 10, as discussed in the 112(a) written description rejection above, these are functional properties that do not further limit the structure of the claimed vector/gene. As such, absent evidence to the contrary, the structure disclosed by Stanford would inherently be able to carry out functions such as having cytotoxicity to cells for lentiviral packaging. Further, the Applicant notes that CASP2 possesses the functional properties as described in the claims (see Applicant’s response to restriction, page 2).
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Stanford as applied to claims 1, 2, 5, 6, and 8-14 above, and further in view of Massie et al. (US20040205834A1, published 10/14/2004).
As shown above, the base claims are obvious over the base art.
Stanford is silent on the distance of a CuO element inserted into a gene expression cassette and a TATA box of the promoter. However, Stanford teaches the vector comprising a CMV promoter, the same promoter present in the vectors disclosed in the instant specification, which are noted to possess a TATA box (see [0023] and Fig. 15 of instant specification).
An Artisan, interested in the Cumate-CuO regulable system, would be aware of Massie et al. for teaching a Cumate-inducible expression system for eukaryotic cells.
Massie et al. teaches an engineered vector virus comprising a) a mammalian promoter sequence (such as CMV) having a TATA element; b) at least one CymR operator sequence positioned 3′ to the TATA element; and c) a gene, such as for example a transactivator, lying 3′ to said operator and operably linked to said promoter (claims 13 and 14 of Massie et al.). In Massie et al., operator sequences are placed further away from the TATA box (19 or 40 bases from the TATA) [0122].
It would have been obvious to one of ordinary skill in the art to modify the vector disclosed by Stanford by placing the CuO element 40 nucleotides from a TATA box of the promoter as taught by Massie et al. and arrive at the claimed invention. One would have a reasonable expectation of success because both Stanford and Massie utilize the CMV promoter. An artisan would be motivated to make this modification because as taught by Massie et al., the operator sequences placed further away from the TATA box (e.g., 40 bases from the TATA) are able to mediate repression by the repressor very effectively. Further, Massie et al. notes that the positioning of the operator site should not be restricted to specific sites, as other sites may be found acceptable by one skilled in the art by simple routine testing [0122].
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M JOHNSON whose telephone number is (703)756-1396. The examiner can normally be reached Monday-Friday 9am-5pm.
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ALLISON M. JOHNSON
Examiner
Art Unit 1638
/ALLISON MARIE JOHNSON/ Examiner, Art Unit 1638
/ROBERT M KELLY/ Primary Examiner, Art Unit 1638
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