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 .
Specification
The disclosure is objected to because of the following informalities:
Regarding the instant specification, the specification makes reference to FIGs. 1-9 (see pg. 2-7); however, drawings have not been filed in the present application.
Appropriate correction is required.
Claim Objections
Claim 12 objected to because of the following informalities:
Regarding claim 12, the claim recites “Administering” in line 3 of the claim. Examiner suggests amending the claim such that the term “Administering” is not capitalized.
Appropriate correction is required.
Claim Interpretation
Regarding claim 12, the claim is broadly directed towards a method for treating a neurological disease comprising administering to a subject an isolated 5’UTR of a Gpr151 gene or a variant thereof, wherein the variant includes nAAGmA in a wild-type sequence of 5’UTR of a Gpr151 gene, wherein n is c, g, or u, and m is a, u, or g. Thus, the broadest reasonable interpretation of claim 12 comprises two claimed embodiments that can be used to treat a neurological disease: 1) a first embodiment comprising a method that can utilize a genus of isolated 5’UTRs of a Gpr151 gene, including fragments of the 5’ UTR of a Gpr151 gene that are of any length; and 2) a second embodiment comprising a method that can utilize a narrower genus of 5’UTRs of a Gpr151 gene that must comprise an nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g.
Claim Rejections - 35 USC § 112
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 12-13, 15, and 17-20 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 make and/or use the invention.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Wands states, on page 1404:
Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex part Forman. They 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 these in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
Regarding the first embodiment of claim 12, the claim does not describe any specific structure that the 5’ UTR of a Gpr151 gene, or a fragment thereof, must comprise in order to be utilized in a method of treating a neurological disease associated with a nerve injury. Further, the instant specification recites explicit experimentation that must be performed in order to determine if a 5’UTR of a GPR151 gene can be utilized to treat a neurological disease caused by nerve injury.
The state of the art, the unpredictability of the art, and the relative skill of the ordinary artisan
Regarding the first embodiment of the claim, it is established in the closest prior art that the structure of 5’ UTRs of a Gpr151 gene can vary and that the possible fragments of a 5’UTR of a Gpr151 gene are very large and neither the fragments nor the entire 5’ UTR of the Gpr151 gene require the claimed nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g.
“NM_194251” (National Library of Medicine Accession No. 194251; published 12 December 2019) is directed towards a Gpr151 mRNA molecule that comprises a 5’ UTR region that is 68 nucleotides in length and does not comprise the claimed nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g (pg. 3-4).
Thus, the closest prior art teaches that the claimed structure of the 5’UTR of a Gpr151 gene is not limited to a 5’ UTR of a Gpr151 gene that comprises an nAAGmA motif, present in the claimed variant, and that there exists a large number of possible fragments of 5’ UTRs of a Gpr151 gene that fall within the claimed genus of 5’ UTRs of a Gpr151 gene.
The amount of direction or guidance presented and the amount of experimentation required.
Regarding the first embodiment of the claim, the instant specification does not provide an adequate amount of direction or guidance regarding the treatment of a neurological disease through the use of a 5’UTR of a GPR151 gene.
The instant specification teaches that isolated 5’ UTRs of Gpr151 genes can bind to a potential negative regulator of axon regeneration, CSDE1, in order to promote axon regeneration through the claimed nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g ([00114]-[00126]). The instant specification teaches the use of 6 different isolated 5’ UTRs of a Gpr151 gene, selected from SEQ ID NOs: 1-3, 7-8, and 10 ([0097]; see Table 1) that could interact with CSDE1 and promote axon regeneration through the use of the claimed nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g ([00137]).
However, the specification teaches the use of 5’ UTRs of a Gpr151 gene that could not promote axon regeneration ([00116], [00121], [00126], [00128]-[00129]; see SEQ ID NOs: 4, 6, and 9 in Table 1). The instant specification teaches that SEQ ID NO: 4 was directed towards a 5’UTR of Gpr151 that did not comprise a CSDE1 binding motif and could not promote axon regeneration via the binding of the 5’ UTR to CSDE1 (pg. 28-29, [00116]; see Table 1). The instant specification teaches that SEQ ID NO: 6 was directed towards the shortest possible fragment of a 5’UTR of a Gpr151 gene that did not comprise the CSDE1 binding motif and could not bind to CSDE1 in order to promote axon regeneration (pg. 28-29, [00121], [00126]; see Table 1). The instant specification teaches that SEQ ID NO: 9 was directed towards a mouse 5’UTR of Gpr151 that did not comprise a CSDE1 binding motif and could not bind to CSDE1 in order to promote axon regeneration [00128]-[00129] (pg. 28-29, [00129]-[00130]; see Table 1).
Therefore, as taught in the specification, performing the claimed method to treat a neurological disease via the use of a 5’ UTR of a GPR151 gene requires experimentation in order to determine if the 5’ UTR of a Gpr151 gene binds to CSDE1 in order to promote axon regeneration. Therefore, the instant specification does not provide an adequate amount of direction or guidance regarding the ability of a 5’ UTR of a GPR151 gene to be utilized to treat a neurological disease.
Accordingly, the amount of experimentation required in order to perform the claimed method in order to treat a neurological disease associated with a nerve injury via the use of a 5’UTR of a Gpr151 gene is very large in view of the claimed method and the guidance in the instant specification teaching that there are 5’ UTRs of a Gpr151 gene, and fragments thereof, that did not promote axon regeneration in order to treat a disease associated with a nerve injury.
Nature of the invention, the presence or absence of working examples, and the breadth of the claims
With regard to the first embodiment of the claim, while the specification does provide potential for the use of 6 different isolated 5’ UTRs of a Gpr151 gene, selected from SEQ ID NOs: 1-3, 7-8, and 10 ([0097]; see Table 1) that comprise the claimed nAAGmA motif that could interact with CSDE1 and promote axon regeneration ([00137]), it is noted that the instant specification also teaches the use of 5’ UTRs of a Gpr151 gene that, following screening of cells that were administered the 5’ UTRs of a Gpr151 gene, did not promote axon regeneration ([00116], [00121], [00126], [00128]-[00129]; see SEQ ID NOs: 4, 6, and 9).
Because the instant specification does not contain a detailed description of how to make and use the method as claimed in the first embodiment of the claim (i.e., a broad method of treating a neurological disease comprising the use of a very broad genus of 5’ UTRS of a Gpr151 gene, or fragments thereof), and absent working examples that provide evidence that is reasonably predictive of the ability of a person of ordinary skill in the art to treat a neurological disease caused by a nerve injury as claimed, the claims are not enabled commensurate in scope with the claimed invention.
Regarding dependent claims 13, 15, and 17-20, the claims are dependent on claim 52 and do not rectify the enablement rejection above. Accordingly, claims 13, 15, and 17-20 are also rejected under 35 U.S.C. 112(a).
Subject Matter Eligibility
Regarding claims 10-11, the claim is eligible subject matter under 35 USC 101 because the claimed polynucleotide is isolated. Accordingly, the claimed isolated polynucleotide is not drawn towards a naturally occurring product. The claimed isolated polynucleotide also has adequate written description support in the instant application, as required by 35 USC 112(a), because the instant specification teaches the use of 6 different isolated 5’ UTRs of a Gpr151 gene, selected from SEQ ID NOs: 1-3, 7-8, and 10 ([0097]; see Table 1) that could interact with CSDE1 and promote axon regeneration ([00137]).
Regarding the closest prior art, Ramakrishnan (PG Pub No. WO 01/68843 A1) is directed towards an invention concerned with human galanin receptor-like GPCR and reagents which bind to human galanin receptor-like gene products (Abstract). Ramakrishnan teaches the use of a galanin receptor-like polypeptide that is 1549 bp in length and comprises a sequence that has 89.6% identity to the claimed SEQ ID NO: 10 (see Fig. 1 and SEQ ID NO: 1 in attached sequence alignment). However, neither Ramakrishnan nor the prior art teaches or suggests the use of an isolated polynucleotide comprising the claimed SEQ ID NOs: 7 or 10 (see Claims 10-11).
Regarding claim 12, the second embodiment present in claim 2 (i.e., a method that can utilize a narrower genus of 5’UTRs of a Gpr151 gene that comprise an nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g) is sufficiently enabled and described in the specification as required by 35 USC 112(a).
The instant specification teaches that isolated 5’ UTRs can bind to a potential negative regulator of axon regeneration, CSD1, in order to promote axon regeneration ([00114]-[00126]). The instant specification teaches that 5’ UTRs of Gpr151 comprise a consensus CSDE1-binding sequence nAAGmA that allow for the 5’ UTR of Spr151 to interact with CSDE1 through its 5’UTR ([00115]). The instant specification teaches the identification of three consensus CSDE1-binding motifs selected from UAAGAA for human Gpr151-5'UTR, CAAGAA for mouse, and UAAGAA for rat, each positioned +11 to +16 from a transcription start site ([0045]). The instant specification teaches the use of 6 different isolated 5’ UTRs of a Gpr151 gene, selected from SEQ ID NOs: 1-3, 7-8, and 10 ([0097]; see Table 1) that comprise the claimed nAAGmA motif that could interact with CSDE1 and promote axon regeneration ([00137]). The specification also teaches that utilizing an artificial RNA comprising a 4X repeat of the CAAGAA sequence was sufficient for the artificial RNA to bind to CSDE1 ([00116]; see SEQ ID NO: 5).
Accordingly, the instant specification provides adequate written description and enablement support for the narrower genus of 5’ UTRS of a Gpr151 gene that comprise an nAAGmA motif, wherein n is c, g, or u, and m is a, u, or g.
Regarding claim 14, the claimed polynucleotides and variants have adequate written description support in the instant application, as required by 35 USC 112(a), because the instant specification teaches the use of 6 different isolated 5’ UTRs of a Gpr151 gene, selected from SEQ ID NOs: 1-3, 7-8, and 10 ([0097]; see Table 1) that could interact with CSDE1 and promote axon regeneration ([00137]).
Regarding the closest prior art, Ramakrishnan (PG Pub No. WO 01/68843 A1) is directed towards an invention concerned with human galanin receptor-like GPCR and reagents which bind to human galanin receptor-like gene products (Abstract). Ramakrishnan teaches the use of a galanin receptor-like polypeptide that is 1549 bp in length and comprises a sequence that has 100% identity to the claimed SEQ ID NO: 1 (see Fig. 1 and SEQ ID NO: 1 in attached sequence alignment). However, neither Ramakrishnan nor the prior art teaches or suggests the administration of an isolated 5’ UTR of a Gpr151 gene, or that the claimed SEQ ID NO: 10 was present within the 5’ UTR region of a Gpr151 gene comprising the claimed SEQ ID NOs: 1-3 such that it could be isolated and administered to a subject to treat a neurological disease (see Claim 14).
Regarding claim 16, the claimed polynucleotides and variants have adequate written description support in the instant application, as required by 35 USC 112(a), because the instant specification teaches the use of 6 different isolated 5’ UTRs of a Gpr151 gene, selected from SEQ ID NOs: 1-3, 7-8, and 10 ([0097]; see Table 1) that could interact with CSDE1 and promote axon regeneration ([00137]).
Regarding the closest prior art, Fincher (PG Pub No. US 2004/0123338 A1) is directed towards an invention concerned with expressed Sequence Tags (ESTs) isolated from cotton (Abstract). Fincher teaches the use of a purified nucleic acid molecule that is 353 bp in length and comprises a sequence is complementary to a sequence that has 94.4% identity to the claimed SEQ ID NO: 8 (pg. 28; see SEQ ID NO: 3353 in attached sequence alignment). However, neither Fincher nor the prior art teaches or suggests the use of an isolated polynucleotide consisting of the claimed SEQ ID NOs: 7-8 or 10 (see Claim 16).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636