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 .
1. Claims 1-12 are pending in the instant patent application.
Claims 1-12 are under examination.
Sequence compliance
2. 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 through 1.825. Specifically, no sequence listing has been provided for sequences identified by reference to SEQ ID NO: 11-15 of the instant specification. (Note that currently the Sequence Listing contains only 10 sequences). In case these sequences are new, Applicant needs to provide a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, a substitute paper copy of that “Sequence Listing”, an amendment directing the entry of that paper copy into the specification, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821 (e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.825(d). The instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (SEQ ID NO: ) be made in the specification and claims wherever a reference is made to that sequence. See MPEP 2422.04.
Specification
3. The use of the terms, which are trade names or marks used in commerce, has been noted in this application, see p. 4. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is advised to review the entire text of the instant patent application for proper use of trade names.
Claim Objections
4. Claim 1 is objected to because of the following informalities:
The claim recites “NLRP3” without first providing the full name of the term. It is suggested that the term be spelled out at its first use and in all independent claims so that it is clearly understood what it stands for. Appropriate correction is suggested.
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.
5. Claims 2, 5, 6, 11 and 12 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.
6. Claim 2 recites nucleic acid sequences represented by SEQ ID NO: 1, 2 and 3. It is noted that SEQ ID NO: 1 and 3 are identical. Thus, reference to three nucleic acids—SEQ ID NO: 1, 2 or 3— within the complex, in which SEQ ID NO: 1 and 3 are the same, renders the claimed subject matter indefinite.
7. Claim 5 is indefinite wherein it recites functional language. The Office has issued new guidance May and September 2016, which has been incorporated into the current MPEP rewrite dated August 2017, at section 2173.05(g), wherein it states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.” In the instant case, the claim recites a substance and then defines it by functional language—"for facilitating escape to a 5’-end or 3’-end of each nucleic acid.” While a functional limitation can provide a patentable distinction (limit the claim scope) by imposing limits on the function of a structure, material or action, in the instant case it is unclear what material/structural or manipulative differences are encompassed by reciting the intended function of the substance. Since the claim fails to meet the criteria set forth in MPEP 2173.05(g), then the claim is rejected as being indefinite.
8. Similarly, claim 11 is indefinite wherein it recites functional language, see “capable of.” It is not clear and cannot be determined from the specification as filed what material limitations of the recited nucleic complex define its capability of penetrating a blood-brain barrier.
9. Claim 12 recites the limitation "the dementia" in claim 1. There is insufficient antecedent basis for this limitation in the claim because claim 1 is limited to “Alzheimer’s dementia,” which does not encompass diseases presently recited within claim 12, absent of evidence to the contrary.
10. Claim 6 is indefinite for being dependent from indefinite claim.
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.
11. Claims 1-3 and 5-12 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.
Claims 1-3 and 5-12 encompass, as critical active ingredients necessary to practice the claimed invention, cell-permeable nucleic acid complexes in which a bioactive nucleic acid targeting an NLRP3 gene and a nucleic acid encoding a carrier peptide are complementary bound to each other. Further, claims 5 and 6 specifically recite substances for facilitating endosomal escape to a 5’-end or 3’-end of each nucleic acid of the nucleic complexes. The claims do not require that these bioactive nucleic acids targeting an NLRP3 gene, nucleic acids encoding a carrier peptide and substances for facilitating endosomal escape possess any particular conserved structure or other disclosed distinguishing feature. Thus, the claims are drawn to a genus of molecular compounds that is defined only by reference to their desired intended function. However, the instant specification fails to describe the entire genus of nucleic acids and substances, which are encompassed by these claims.
MPEP §2163(I)(A) states:
“The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional or known in the art. Consider the claim "A gene comprising SEQ ID NO:1." The claim may be construed to include specific structures in addition to SEQ ID NO:1, such as a promoter, a coding region, or other elements. Although SEQ ID NO:1 is fully disclosed, there may be insufficient description of other structures embraced by the claim (e.g., promoters, enhancers, coding regions, and other regulatory elements).”
“An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. For example, the amino acid sequence of a protein along with knowledge of the genetic code might put an inventor in possession of the genus of nucleic acids capable of encoding the protein, but the same information would not place the inventor in possession of the naturally-occurring DNA or mRNA encoding the protein. See In re Bell, 991 F.2d 781, 26 USPQ2d 1529 (Fed. Cir. 1993); In re Deuel, 51 F.3d 1552, 34 USPQ2d 1210 (Fed. Cir. 1995) (holding that a process could not render the product of that process obvious under 35 U.S.C 103).”
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. In this case, the only factor present in the claims is a reference to intended functions—to target an NLRP3 gene, to encode a carrier peptide and to facilitate endosomal escape. There is not even identification of any particular portion of the structure that must be conserved to sustain the function of a cell-permeable nucleic acid complex suitable for clinical administration to prevent, ameliorate and treat dementias, as currently in claims. The specification does not provide a complete structure of those cell-permeable nucleic acid complexes in which a bioactive nucleic acid targeting an NLRP3 gene and a nucleic acid encoding a carrier peptide are complementary bound to each other, or those substances for facilitating endosomal escape to a 5’-end or 3’-end of each nucleic acid of the nucleic complexes. There is also no clear understanding of a representative number of species for the recited genus (those bioactive nucleic acids targeting an NLRP3 gene, nucleic acids encoding carrier peptides are complementary bound to each and further bound with substances for facilitating endosomal escape to a 5’-end or 3’-end of each nucleic acid to create cell-permeable nucleic acid complexes all suitable for clinical purposes). Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of nucleic acid complexes, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, only the nucleic acid complexes with specifically identified structure, such as in claim 4, but not the full breadth of the claim meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
12. Claims 1-12 are further 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 make and/or use the invention.
Claims 1-12 are directed to methods of preventing, ameliorating and treating different types of dementia and specifically Alzheimer’s dementia, (AD). The treatment encompasses administration of cell-permeable nucleic acid complexes in which a bioactive nucleic acid targeting an NLRP3 gene and a nucleic acid encoding a carrier peptide are complementary bound to each other, and further bound to a substance for facilitating endosomal escape to a 5’-end or 3’-end of each nucleic acid of the nucleic complexes. However, the specification does not provide sufficient guidance to enable practice the full scope of the claimed invention without undue experimentation.
The enablement requirement is met when one skilled in the art, having read the specification, could practice the invention without “undue experimentation.” Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d at 1336 (Fed. Cir. 2013). The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
The specification asserts that targeting NLRP3 gene by providing a complex that is blood-brain permeable, such as the nucleic acid complex in which a bioactive nucleic acid targeting NLRP3 and a carrier peptide nucleic acid complementary bound to each other, is effective in preventing and treating dementia, pp. 2-7. The experimental results, Figures 1-4 and pp. 34-54, demonstrate changes in expression of NLRP3 in BV-2 microglia cell line and primary culture of mouse microglia after treatment with the nucleic acid complex comprising nucleic acids of Table 4, p. 49, SEQ ID NOS: 1, 3, 10 and 14, (Fig. 1-2, Example 2-2, 3-1); the same when the cells are pretreated with LPS/ATP, a model for elevated immune response, (Fig. 3 and Example 3-2, 4); and the same responses plus changes in the expression of p-tau, (Fig. 4). Example 5, pp. 49-54, discloses experiments of administration of the nucleic acid complexes comprising nucleic acids of SEQ ID NO:1, 3, 10 and 14 to SD rats to ascertain the effects of inhibiting NLRP3 gene in vivo microglia. The primary culture of rat microglia in this experiment were further treated with LPS and ATP to initiate inflammatory response similar to the one in AD pathology, Example 5-(2, 3, 4 and 5), Fig. 4A. The data show the decrease in expression of the target NLRP3 gene, p. 53 specifically. The specification fails to provide any further information, such as factual evidence or a line of sound scientific reasoning, to support a conclusion that administration of a cell permeable nucleic acid complex in which a nucleic acid targeting an NLRP3 gene and a carrier peptide nucleic acid complementarily bound to each other to a subject suffering from dementia or AD in particularly would have a specific preventive or actual treatment clinical benefit.
The nature of the invention involving biological molecules and their effect on a physiological system is complex and unpredictable. This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology", Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).
The prior art recognizes a significant pathological role of beta amyloid in etiology of AD. An NLRP3 inflammasome and its presence within microglia has been described within relevant art, see paragraph [6] of the specification. However, finding of NLRP3 as being associated with a pathology of dementia in general has not been reported. It is also not recognized in the art that diseases recited within claim 12 have a common pathophysiological pathway specifically related to NLRP3 gene.
With respect to claim breadth, the standard under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing the enablement scope of the claims, the teachings of the specification are to be taken into account because the claims are to be given their broadest reasonable interpretation that is consistent with the specification (see MPEP 2111 [R-1], which states that claims must be given their broadest reasonable interpretation “During patent examination, the pending claims must be "given *>their< broadest reasonable interpretation consistent with the specification." In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).”
As such, the broadest reasonable interpretation of the claimed method is that it allows treatment and prevention of AD as well as vascular dementia, Parkinson’s and Lewy body dementias, dementia caused by Huntington’s disease, CJD and Pick’s disease by administration of nucleic acid complex compounds that are not described at the time filing, see section 11 earlier. Thus, the claims encompass treatment of an unreasonable number of pathological conditions of different etiology and epidemiology, which the skilled artisan would not know how to evaluate. As opposed to the claims, what is disclosed about the claimed method is narrow: a set of working examples using microglia cell lines and primary cultures of microglia to evaluate the changes in expression of NLRP3 gene under treatment by nucleic complex comprising nucleic acids of SEQ ID NO: 1, 3, 10 and 14, and no other obvious specific examples of bioactive nucleic acid molecules targeting an NLRP3 gene, art recognized animal or cell models for specific recited pathologies, or any other meaningful guidance as how to practice the full scope of instant claimed method.
Applicant has left those skilled in the art with too much experimentation to research and discover for themselves the effect, if any, of administration of a cell-permeable nucleic acid complex in which a bioactive nucleic acid targeting an NLRP3 gene bound to a carrier peptide nucleic acid to a patient suffering from dementia or specifically from AD. The art does not teach that NLRP3 is directly associated with pathology of dementia. The specification does not teach how to make decisions about the effective doses, or specific routes and regimes of administration, or how to determine when a compound is actually targeting the specific areas associated with pathology of dementia. There is also no information related to any preventive measures with respect to dementia, as currently in claims. As such, Applicant has merely provided a starting point for research and experimentation and not a meaningful enabling disclosure of how to practice the claimed invention. In fact, the specification does not describe a single embodiment that satisfies the claims’ limitations.
A mere wish or plan of obtaining the claimed invention is not sufficient. The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held 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” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure.” The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art,” “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement.”
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed methods without first making a substantial inventive contribution to perfect the method and complete the invention.
Conclusion
13. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA N CHERNYSHEV whose telephone number is (571)272-0870. The examiner can normally be reached 9AM to 5:30PM, Monday to Friday.
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/OLGA N CHERNYSHEV/ Primary Examiner, Art Unit 1675
February 11, 2026