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 .
Claims status
Applicants preliminary amendment to the claims filed 7/17/2024 is acknowledged.
Claims 6 was cancelled and claims 12-19 was newly added. Claims 1-5, 7-19 is/are currently pending and under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because of use of legal phraseology. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because of the following informalities: Page 3, line 2 appears to have a typographical error, reciting “said isolated nucleic acid molecule specifically leads to the expression in a particular population of CRN1-positive cells in layer 2/3 of mouse cortex” (emphasis added). The remainder of the specification identifies the population as “EGR2-positive cells”. Appropriate correction is required.
The disclosure is objected to because of the following informalities: Page 22, line 4 references “(fig. 2)” as showing immunohistochemistry data. However, this data is shown in Figure 1. Additionally the unit of thickness for the slices is misspelled as “microm”. Correct spelling/abbreviation is “micrometer” or “micron” or “um”. Appropriate correction is required.
Claim Objections
Claim 7 is objected to because of the following informalities: Claim recites “A method of expressing an exogenous gene comprising the steps of” (emphasis added). Since this is the first recitation of any step in this method claim, use of “the” as an article is inappropriate. Further, since only step is recited, use of the plural (“steps”) is inappropriate. Following correction is recommended: “A method of expressing an exogenous gene comprising a step[[s]] of”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-5, 7-19 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “An isolated nucleic acid comprising the nucleic acid sequence of SEQ ID NO: 1, or a nucleic acid sequence of at least 700 bp having at least 80% identity to said sequence of SEQ ID NO:1”, and the claim also recites “An isolated nucleic acid consisting of the nucleic acid sequence of SEQ ID NO: 1, or a nucleic acid sequence of at least 700 bp having at least 80% identity to said sequence of SEQ ID NO:1” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 1 recites a particular population of EGR2-positive cells “being characterized in that it also expresses ACTA2, ADORA3 and MYH11”. It is unclear if the particular population of EGR2-positive cells actually expresses ACTA2, ADORA3 and MYH11 or are they simply being characterized to identify if they express ACTA2, ADORA3 and MYH11. Thus, the identity of the claimed particular population of cells is unclear. For the purpose of compact prosecution, the claim(s) 1 is/are interpreted as “said particular population of EGR2-positive cells
Claims 2-5, 7-19 is/are rejected due their dependence on claim 1 because they do not clarify the 112b issue noted with claim 1.
Regarding claim 2, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 12-14, 19 is/are rejected due their dependence on claim 2 because they do not clarify the 112b issue noted with claim 2.
Regarding claims 10, 14-18, the phrase "for instance" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(a)
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.
Written Description
Claims 1-5, 7-19 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.
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112(a) or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of.
Claim 1 is directed to an isolated nucleic acid that could be limited to (“consisting of”) a nucleic acid of SEQ ID NO: 1 or a 700bp nucleic acid sequence that is at least 80% identical to SEQ ID NO: 1. Claim 1 also embraces isolated nucleic acids that in addition to the nucleic acid of SEQ ID NO: 1 or a 700bp nucleic acid sequence that is at least 80% identical to SEQ ID NO: 1 include additional sequences (“comprising of”).
SEQ ID No: 1 is a 800bp nucleic acid sequence that was serendipitously created by the Applicant (page 2, para 3; page 4, para 7). In claiming a 700bp nucleic acid sequence that is at least 80% identical to SEQ ID NO: 1, the claim embraces any 700bp fragment of SEQ ID NO: 1 and/or any 700bp sequence that differs from SEQ ID NO: 1 by as much as 160bp since 20% variability is allowed by the claim. Any 160bp may be varied. Thus, claim 1 embraces a wide array of sequences that are not limited to the recited SEQ ID NO: 1 but embrace any additional sequences and/or any 700bp fragment of SEQ ID NO: 1 and/or any 700bp sequence that differs from SEQ ID NO: 1 by as much as 160bp.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by “whatever characteristics sufficiently distinguish if). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G. D. Searie & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004). See MPEP § 2163.
In the instant case, the specification discloses SEQ ID NO: 1. However fails to disclose any fragment or variant of this sequence. Thus, the specification does not disclose the structure of any of the nucleic acids embraced by a 700bp nucleic acid sequence that is at least 80% identical to SEQ ID NO: 1. Furthermore, the specification does not disclose any distinguishing identifying characteristics of the claimed nucleic acid sequence that provide for the claimed property (“wherein said isolated nucleic acid molecule leads to the specific expression […]”). No structure-function relationship between the structure of SEQ ID NO: 1 and its alleged function of cell-specific expression is disclosed such that an artisan could identify nucleotides in SEQ ID NO: 1 that are required and thus must be retained. Similarly, an artisan could not identify nucleotides in SEQ ID NO: 1 that could be varied and yet retain the alleged function. 700bp sequences with less than 100% identity, especially only 80% identity as embraced by the claims, can vary substantially. Yet, there is no teaching in the specification that a 700bp fragment of SEQ ID NO: 1 or any 700bp sequence that shares 540-700bp with SEQ ID NO:1 would retain the alleged function of SEQ ID NO: 1.
According to the MPEP § 2163, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").”
In the instant case, as noted above, no representative specie is disclosed for a 700bp nucleic acid sequence that is at least 80% identical to SEQ ID NO: 1 even though a substantial variation of species exists within the claimed genus of 700bp nucleic acid sequence that are at least 80% identical to SEQ ID NO: 1. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited genus.
Therefore, claim 1 lacks written description support for an isolated nucleic acid sequence comprising or consisting of a 700bp nucleic acid that is at least 80% identical to SEQ ID NO: 1.
Since claims 2-5, 7-19 embrace an isolated nucleic acid sequence comprising or consisting of a 700bp nucleic acid that is at least 80% identical to SEQ ID NO: 1, these claims 2-5, 7-19 also lack written description support for an isolated nucleic acid sequence comprising or consisting of a 700bp nucleic acid that is at least 80% identical to SEQ ID NO: 1.
In addition to the limitation noted above that lacks written description support, claims also embrace isolated nucleic acid sequences that comprise or consists of SEQ ID NO: 1 “wherein said isolated nucleic acid molecule leads to the specific expression in layer 2/3 of mouse cortex of an exogenous gene in a particular population of EGR2-positive cells when a nucleic acid sequence coding for said exogenous gene is operatively linked to said isolated nucleic acid molecule, said particular population of EGR2-positive cells being characterized in that it also expresses ACTA2, ADORA3 and MYH11.”
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. However, in the instant case, the specification does not support that SEQ ID NO: 1 leads to the specific expression in layer 2/3 of mouse cortex of an exogenous gene in a particular population of EGR2-positive cells that also expresses ACTA2, ADORA3 and MYH11 (see claim interpretation is 112b rejection above).
The specification defines “"Specific expression" of an exogenous gene, also referred to as "expression only in a certain type of cell" means that at least more than 75%, preferably more than 85%, more that 90% or more than 95%, of the cells expressing the exogenous gene of interest are of the type specified, i.e. the particular population of the cells expressing EGR2 in the present case” (page 6, last para). Thus, the claim requires SEQ ID NO:1 to drive transgene expression in at least 75% of the cells in the claimed “particular population” of EGR2-positive cells. The claim requires the cells to express EGR2 and for SEQ ID NO: 1 to drive expression in a subset (“particular population”) of these EGR2-positive cells, wherein the subset is identified by expression of ACTA2, ADORA3 and MYH11 in these cells. However, the specification provides no support that such a “particular population” exists. In the examples provided, GFP+ and GFP- cells collected from layers I-VI of mouse cortex were sorted using FACS (page 22, para 2). GFP+ cells should be cells expressing the GFP transgene under SEQ ID NO: 1 or Ef1a promoter (page 21, para 4, 5). Top ten genes that are differentially expressed in GFP+ in comparison to GFP- cells is shown on page 22. No clear indication is provided if these 10 genes is up or down regulated or if the GFP+ cells are only those cells transfected with the vector comprising SEQ ID NO: 1 or if EF1a-GFP cells are also included. Critically, there is no indication that there exists a cell type that expresses each of ACTA2, ADORA3 and MYH11. Furthermore, there is no indication that there exists a Egr2-positive cell type that expresses each of ACTA2, ADORA3 and MYH11. Figure 2 is RNA seq data from GFP- and GFP+ cells that were transfected with vector comprising SEQ ID NO: 1 (page 4). It shows higher counts per million of Egr2 mRNA expression in GFP+ cells vs GFP- cells. However, this data does not show that at least 75% of GFP+ cells have Egr2 mRNA such that it can be inferred that SEQ ID NO: 1 leads to the specific expression in EGR2 positive cells. Furthermore, since there is no evidence regarding how many GFP+ cells are also EGR2+, there is no evidence that an overlap exists between the cells that are EGR2+ and the cells that are positive for any one of ACTA2, ADORA3 and MYH11. Thus, a skilled artisan cannot reasonably conclude that the claimed SEQ ID NO: 1 leads to the specific expression in layer 2/3 of mouse cortex of an exogenous gene in a particular population of EGR2-positive cells that also expresses ACTA2, ADORA3 and MYH11. The disclosed examples do not support that the claimed SEQ ID NO: 1 has the claimed function. Thus, examples disclosed cannot be deemed “actual reduction to practice”. Furthermore, as noted above, distinguishing identifying characteristics of the claimed SEQ ID NO: 1 and a structure-function relationship is lacking in the specification, such that a skilled artisan cannot envision a nucleic acid sequence with the claimed function.
Therefore, the claimed invention, as a whole, is not adequately described. The claims require essential or critical elements which are not adequately described in the specification, and are not conventional in the art before the effective filing date.
Enablement
Claims 1-5, 7-19 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” See MPEP § 2164. These factors include, but are not limited to: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The office has analyzed the specification in direct accordance to the factors outlines in In re Wands. MPEP 2164.04 states: “[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection.” These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform “undue experimentation” to make and/or use the invention and therefore, applicant’s claims are not enabled.
(A) With respect to the breadth of the claims: Claims 1, 2, 10, 14 are directed to an isolated nucleic acid comprising or consisting of a nucleic acid of SEQ ID NO: 1 or a 700bp nucleic acid sequence that is at least 80% identical to SEQ ID NO: 1. The claimed function and/or use of these nucleic acid sequences is to lead to a specific expression of a transgene in a specific population of cells in layer 2/3 of mouse cortex. The specific population is a EGR2+ cells that also express ACTA2, ADORA3 and MYH11. Per the definition of “specific expression” in the specification on page 6, the claim requires the claimed nucleic acid to lead to transgene expression in at least 75% of the cells in the claimed specific population of cells.
Claim 3-5 ,12, 15, 16 are directed to an expression cassette or a vector comprising the isolated nucleic acid of claim 1 or 2 in operable linkage with a transgene, and also require the claimed function and/or use of these nucleic acid sequences.
Claim 11, 19 is directed to a kit comprising the isolated nucleic acid of claim 1 or 2. Although these kit claims do not explicitly recite a function or use, the specification does not disclose any other use of the claimed nucleic acid. The only use disclosed for the claimed nucleic acid is to label “a particular EGR2-positive cells population” (page 2, para 3; page 3, paras 3, 5; page 4, paras 1, 3, 6; page 6, paras 2, 4, 5, 7; page 7, para 5; page 17, para 1; page 19, para 5). Thus, the specification envisions only one use of the claimed nucleic acid and thus only one of the claimed kit.
However, as is analyzed below, the specification does not enable the claimed use/function. Thus, the specification does not enable an artisan to use the claimed nucleic acid, expression cassette, vector or kit.
Claim 7, 17 is directed to a method using the expression cassette of claim 3 to drive transgene expression in any isolated cell, any cell line or any cell population which could be in vitro or in vivo (see page 4 disclosing a tissue as a cell population). Consequently, the breadth of the claims is expansive.
Claim 8, 9, 13, 18 are directed to any type of isolated cell with the expression cassette of claim 3 or vector of claim 4. Consequently, the breadth of the claims is expansive.
Although these method or isolated cell claims do not explicitly recite that the transfected cells are EGR2, ACTA2, ADORA3 and/or MYH11 positive, the specification does not disclose any other method of use of the claimed nucleic acid or any other cell that could express a transgene linked to SEQ ID NO:1. The only method of use disclosed for the claimed nucleic acid is to label “a particular EGR2-positive cells population” (page 2, para 3; page 3, paras 3, 5; page 4, paras 1, 3, 6; page 6, paras 2, 4, 5, 7; page 7, para 5; page 17, para 1; page 19, para 5). Thus, the specification envisions only one method of use of the claimed nucleic acid. However, as noted above and analyzed below, the specification does not enable the claimed use/function.
(B) The nature of the invention: The invention is in the field of synthetic promoters to drive cell specific transgene expression.
(C), (D), (E) With respect to the state of the prior art, the level of one of ordinary skill and predictability of the art: Rational design of synthetic promoters to drive cell-specific transgene expression requires developing large libraries of sequences from previously known natural regulatory sequences and using various prediction tools to identify ideal sequences to cell specific expression. See Methods in Brown et al (Chapter 10: Constructing Strong Cell Type-Specific Promoters Through Informed Design, pg 131, David Gould (ed.), Mammalian Synthetic Promoters, Methods in Molecular Biology, vol. 1651,2017). However, such a task does not necessarily result in cell-specific expression. Juttner et al (Nature Neuroscience | VOL 22 | AUGUST 2019 | 1345–1356; IDS 7/17/2024) designed 230 synthetic promoters for expression in retinal cells using various strategies (page 1346, col. 1, para 4) but only found 32 that had any specificity (page 1346, col. 2, para 1). They used diligent means to identify the cell types labeled by each promoter showing co-staining between transgene driven by the synthetic promoter and a well-known retinal cell marker (Figure 1). As can be seen in this figure, synthetic promoters that were considered specific to a specific cell type drove transgene expression primarily in that cell type and labelled majority of the cells of that cell type. For example, 100% of the cells transduced with ProA1 were cones and ProA1 labelled more than 80% of all the cone cells (Figure 1c, d). Yet, Juttner note that it was unpredictable which cell type a synthetic promoter would label because less than 1% of the synthetic promoters replicated the expression specificity of the source gene such they could not target the chosen cell types (page 1346, col. 2, para 1; page 1352; col. 2, para 6). Furthermore, the probability of a vector comprising their promoter targeting the same cell type in different species was low such that a predictable relationship between promoter and cell type across species cannot be established (page 1352, col. 2, para 5).
Thus, the prior art of rational synthetic promoter design teaches that the synthetic promoter design is complex, requiring high skill and significant experimentation to identify promoters that have some cell specificity. However, even then it remains unpredictable which cell a promoter would label and if the specificity would remain across species.
Regarding Egr2, Nafez et al (Molecular and Cellular Neuroscience 64 (2015) 95–103; IDS 7/17/2024) teaches Egr-2 expression was known in layers II and III of the cortex (page 96, col. 1, para 2) and its expression increases in primary neurons in vitro when stimulated with cytokines such as TNFa (Figure 1).
(F), (G) With respect to the amount of direction and working examples provided by the applicant: The applicants have provided that SEQ ID No: 1 was serendipitously created without any further examination of the structure of these sequence that would allow for transcriptional regulatory activity. In the examples, the specification teaches an AAV2/1 vector comprising SEQ ID NO: 1 as promoter that drives eGFP transgene (page 21). The AAV2/1 vector was injected in mouse cortex and tissue was collected for immunohistochemistry or FACS sorting after 14 days. Immunohistochemistry was performed using a GFAP antibody and not GFP. The data shows that mice injected with a vector comprising EF1a promoter have more GFAP expression in the layers 2/3 of the cortex than the mice injected with a vector comprising SEQ ID NO: 1 (Figure 1). The relevance of this data to the claimed function of driving expression in Egr2+ cells is unknown since cells were not co-labelled for Egr2 and GFP. Such a data is essential to establish the claimed function. See data in Figure 1 of Juttner that shows methods of providing evidence for a cell-specific promoter.
The specification also provides some RNAseq data from FACS sorted GFP+ and GFP- cells (page 22, Figure 2). GFP+ and GFP- cells collected from layers I-VI of mouse cortex were sorted using FACS (page 22, para 2). GFP+ cells should be cells expressing the GFP transgene under SEQ ID NO: 1 or Ef1a promoter (page 21, para 4, 5). Top ten genes that are differentially expressed in GFP+ in comparison to GFP- cells is shown on page 22. No clear indication is provided if these 10 genes is up or down regulated. Thus, there is no evidence that any of these differentially expressed genes, including ACTA2, ADORA3 and MYH11, are markers for the GFP+ cells since each of these could be down regulated. Furthermore, it is not clear if the GFP+ cells are only those cells transfected with the vector comprising SEQ ID NO: 1 or if EF1a-GFP cells are also included. Critically, there is no indication that there exists a cell type that expresses each of ACTA2, ADORA3 and MYH11. Furthermore, there is no indication that there exists a Egr2-positive cell type that expresses each of ACTA2, ADORA3 and MYH11. Figure 2 is RNA seq data from GFP- and GFP+ cells that were transfected with vector comprising SEQ ID NO: 1 (page 4). It shows higher counts per million of Egr2 mRNA expression in GFP+ cells vs GFP- cells. However, this data does not show that at least 75% of GFP+ cells have Egr2 mRNA such that it can be inferred that SEQ ID NO: 1 leads to the specific expression in EGR2 positive cells. Furthermore, since there is no evidence regarding how many GFP+ cells are also EGR2+, there is no evidence that an overlap exists between the cells that are EGR2+ and the cells that are positive for any one of ACTA2, ADORA3 and MYH11.
(H) The specification does not enable a proper use of the claimed nucleic acid sequence, an expression cassette or vector comprising the sequence or a kit with the claimed nucleic acid sequence. Undue experimentation would be required in the use of the claimed nucleic acid due to the amount of experimentation necessary because of the lack of amount of guidance in the form of varied working examples in the specification regarding which cell type the claimed sequence would drive transgene expression in. Although Figure 2, shows that Egr2 mRNA expression is higher in GFP+ cells, this does not show that the claimed nucleic acid is specific to Egr2+ cells. An ordinary artisan would have to perform undue experimentation to test of each of the various cell types and subsets of those cells types in the mouse cortex to identify a use of the claimed nucleic acid. Critically, there is no enablement for a method wherein the claimed nucleic acid could be used to drive transgene expression in any cell type from any species. Juttner teaches unpredictability in identifying if a promoter would drive transgene expression in cell type of choice and especially across species. Undue experimentation would be required to practice the method of use of the claimed nucleic acid due to the amount of experimentation necessary because of the expansive breadth of the claims, the state of the prior art and its unpredictability, and the lack of amount of guidance in the form of varied working examples in the specification.
MPEP §2164.01(a), 4th paragraph, provides that, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1157, 1562; 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Genentech Inc. v. Novo Nordisk A/S, 42 USPQ2d 1001, 1005 (CA FC), states that, “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable,” citing Brenner v. Manson, 383 U.S. 519, 536 (1966) (stating, in the context of the utility requirement, that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion”). The Genentech decision continued, “tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.” Id. at p. 1005.
After applying the Wands factors and analysis to claims 1-5, 7-19, in view of the applicant’s entire disclosure, and considering the In re Wright, In re Fisher and Genentech decisions discussed above, it is concluded that the practice of the invention as claimed in claims 1-5, 7-19 would not be enabled by the written disclosure. Therefore, claims 1-5, 7-19 are rejected under 35 U.S.C. §112(a) for failing to disclose sufficient information to enable a person of skill in the art to use the claimed invention.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MATASHA DHAR whose telephone number is (571)272-1680. The examiner can normally be reached M-F 8am-4pm (EST).
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/MATASHA DHAR/Examiner, Art Unit 1632
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