Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of the Application
Claims 26-45 are pending and are currently under examination.
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 32 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 32 lacks antecedent basis because it recites “the modification” and depends from claim 31 that recites “the non-natural modification”.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 26-45 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification,
while being enabling for demonstrating a guide RNA in which the 5' hairpin of the full-length ACA19 snoRNA, and most of the H box were removed (Figure 4) was capable of supporting the conversion of a uridine to pseudouridine in mouse RNA wherein a the Idua-W392X mutation in the mouse RNA, which corresponds to the human IDUA W402X mutation known to cause Hurler syndrome (Example 3) and a method of converting a PTC in the human CFTR gene to a pseudouridine in vitro using a guide RNA in which the 5' hairpin of the full-length ACA19 snoRNA, and most of the H box were removed (Example 2),
does not reasonably provide enablement for methods of treating any genetic disorder in a human subject in need therefore comprising administering a guide RNA consisting of a single hairpin structure corresponding to one of the two hairpin structures of the wild type H/ACA snoRNA.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The following factors have been considered in the analysis of enablement: (1) the breadth of the claims, (2) the nature of the invention, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims and the nature of the invention:
The broadest reasonable interpretation of the claimed invention is a method of treating any type of genetic disease in a subject in need comprising administering a guide RNA consisting of a single hairpin structure corresponding to one of the two hairpin structures of the wild type H/ACA snoRNA.
Whether the specification would have been enabling as of the filing date involves consideration of the nature of the invention, the state of the prior art, and the level of skill in the art. The state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to the skill of those in the art in relation to the subject matter to which the claimed invention pertains at the time the application was filed. See MPEP § 2164.05(b). The state of the prior art provides evidence for the degree of predictability in the art and is related to the amount of direction or guidance needed in the specification as filed to meet the enablement requirement. The state of the prior art is also related to the need for working examples in the specification.
The state of the prior art:
The state of the art for using snoRNA for treatment of diseases and disorders is in emerging as taught by Li et al. ("Unlocking the life code: a review of SnoRNA functional diversity and disease relevance." Cell Communication and Signaling 23.1 (2025): 266). Li et al. teach snoRNA from H/ACA can interact with a variety of core proteins to form ribonucleoprotein complexes and guide target RNA modification thru complementary base pairing (see Figure 1). Li et al. teach snoRNA are involved in the regulation of mRNA splicing and may interact with precursor mRNA to influence the selection of splicing sites, thereby altering gene expression profiles and further experiment has demonstrated that snoRNA-mediated pseudouridylation can occur on mRNA targets, highlighting the role of snoRNA in the post-transcriptional modification of mRNA (see page 3 second col.).
Further, Li et al. indicates snoRNAs play a critical role in biological research, particularly in RNA modification and gene expression regulation. However, snoRNA research faces several challenges such as the techniques for identifying and characterizing snoRNA targets remain underdeveloped and many snoRNA are active only in specific cell types or developmental stages, which significantly limits a comprehensive understanding of their functions (page 13 last para to page 14).
A review of the prior art does not provide a correlation between administration of a nucleic acid molecule comprising a guide RNA consisting of a single hairpin structure of H/ACA snoRNA and treatment of the vast number of genetic disease as instantly claimed. Furthermore, the prior art does not provide said correlation when using the claimed nucleic acid molecule that caused a conversion of a uridine to pseudouridine in mouse RNA wherein a the Idua-W392X mutation in the mouse RNA, which corresponds to the human IDUA W402X mutation known to cause Hurler syndrome and treatment of Hurler syndrome or any other genetic disorders as broadly claimed.
The level of one of ordinary skill:
While the level of one of ordinary skill practicing said invention would be high, the level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention.
Because the state of the prior art does not provide evidence of the degree of predictability that methods for treating any disorder of genomic disorder in a subject can occur by administering to the subject a guide RNA consisting of a single hairpin structure of H/ACA snoRNA, one of ordinary skill in the art would look for guidance or direction in the instant specification.
The level of predictability in the art:
“The “predictability or lack thereof” in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability.” (MPEP 2164.03).
The amount of direction provided by the inventor:
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. >See, e.g., Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The existence of working examples:
The working embodiment in the instant application describes a guide RNA in which the 5' hairpin of the full-length ACA19 snoRNA, and most of the H box were removed (Figure 4) was capable of supporting the conversion of a uridine to pseudouridine in mouse RNA wherein a the Idua-W392X mutation in the mouse RNA, which corresponds to the human IDUA W402X mutation known to cause Hurler syndrome. The working embodiments do not describe a guide RNA in which the 5' hairpin of the full-length ACA19 snoRNA that would provide treatment for the vast number of disorders of genomic disorders claimed.
The standard of an enabling disclosure is not the ability to make and test if the invention works 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 (MPEP 2164.03 and Chiron Corp. v. Genentech Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1325-26 (Fed. Cir. 2004). The instant invention suggests administration, a guide RNA in which the 5' hairpin of the full-length ACA19 snoRNA, and most of the H box were removed (Figure 4) to a subject to treat any genetic disorder without an enabling disclosure or guidance in the prior art.
While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
The prior art is undeveloped for the role a guide RNA in which the 5' hairpin of the full-length ACA19 snoRNA, and most of the H box were removed (Figure 4) plays in the vast number of genetic diseases claimed and without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Written Description
Claims 26-45 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species 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 functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed 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.
The claims are drawn to a genus of a guide RNAs comprising a single guide region of H/ACA snoRNA with the function of converting a uridine to a pseudouridine in RNA and treating any genetic disorder. The genus further consists of a nucleic acid sequence consisting of a single guide RNA wherein the sequence is any of 50-80 nucleotides in length as in claim 30.
When determining 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. In the instant case, the specification describes conversion of a uridine to pseudouridine in mouse RNA wherein the Idua-W392X mutation in the mouse RNA, which corresponds to the human IDUA W402X mutation known to cause Hurler syndrome using a nucleic acid sequence, as in SEQ ID No. 10, which is 66 nucleotides in length. This example does not encompass the vast number of genetic disorders in which conversion of a uridine to pseudouridine in a RNA can lead to treatment of any genetic disorder using any guide RNA comprising a single hairpin structure of a wild type H/ACA snoRNA consisting of 50-80 nucleotides in length.
It is then determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genera. In the instant case, the only other identifying characteristic is using a guide RNA 66 nucleotides in length that demonstrated conversion of a uridine to pseudouridine in a Idua-W392X mutation in the mouse RNA. The disclosure has not described using any variation of the claimed nucleic acid that causes conversion of a uridine to pseudouridine in RNA that correlates with treatment of any genetic disorders. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant a vast number of nucleic acid sequences, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “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).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every variation of a nucleic acid molecule comprising a guide region consisting of a single hairpin structure corresponding to one of the two hairpin structures of the wild type H/ACA snoRNA with the claimed function of treating any genetic disorder. Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. See In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970);and, In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 26-45 are rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,866,702 (Patent ‘702). Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter
MPEP 804 “A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985). In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
Claims of Patent ‘702 are drawn to nucleic acid molecule comprising a guide region consisting of a single hairpin structure corresponding to one of the two hairpin structures of the wild type H/ACA snoRNA, wherein (i) the nucleic acid molecule is capable of forming a partially double stranded nucleic acid complex with a target RNA in a mammalian cell, wherein the target RNA comprises a target uridine; (ii) the partially double stranded nucleic acid complex is capable of engaging a mammalian pseudouridylation enzyme; (iii) the guide region assists in positioning the target uridine in the partially double stranded nucleic acid complex; and (iv) the target uridine can be converted to a pseudouridine by the mammalian pseudouridylation enzyme.
The instant claims are drawn to methods of treating a genetic disorders in a human subject in need therefore comprising administering a guide region consisting of a single hairpin structure corresponding to one of the two hairpin structures of the wild type H/ACA snoRNA and it would have been obvious to use the nucleic acid molecule of Patent ‘702 in the instant methods.
Subject Matter Free of the Prior Art
The claims are free of the prior art. WO 2007/064952 (of record IDS 01/16/2024) describes engineered snoRNA in compositions that are suitable to direct the pseudouridylation of a target RNA in mammalian cells wherein the guide RNAs are capable of engaging a mammalian pseudouridylation enzyme (see claims 27-49, paragraphs 61, 72, 73). WO 2007/064952 describes shortening or removing nucleotides in the dual hairpin structures but does not suggest or teach a motivation of make a guide RNA comprising just a single hairpin structure of the wild type H/ACA snoRNA. Further one would not have been motivated to make the claimed snoRNA given functional dual hairpin snoRNA structures are demonstrated in the prior art to be capable of pseudouridylation of a target RNA.
Conclusion
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
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