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 .
Applicant’s election without traverse of group I and the species delivery, cholesterol, and intrathecal in the reply filed on 9/6/25 is acknowledged.
Claims 2 and 15-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 9/6/25.
Specification
The disclosure is objected to because of the following informalities: There is a structure on page 48 that is not fully legible.
Appropriate correction is required.
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 1, 3, 6-12, 20, and 21 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.
The instant claims are directed to any double stranded nucleic acid complex with a first strand that is 8-40 nucleotides in length and second strand of any length (i.e. 1000 nucleotides) wherein the first strand comprises a sequence of any length within the 8-40 nucleotides (i.e. 2 nt) that is capable of hybridizing to at least any part of any target gene or any transcription product thereof. The second strand comprises a base sequence of any length (i.e. 3 nucleotides) that are complementary to the first strand, which would result in annealing. The first strand is not necessarily the same length as the second strand and is annealed at any level (i.e. a single nucleotide).
The specification does not adequately describe the structure required for the complex to have the required function of having an antisense effect on the transcription product. The specification discloses fully annealed double stranded nucleic acids of a specific length that have inhibitory effects on a target that is fully complementary to the antisense strand, which is not representative of the instantly recited genus that has minimal specificity to any specific target and encompasses various possible configurations of compounds.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See 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 species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being double stranded nucleic acid complexes with minimal specificity to any specific gene and various possible configurations that would function as claimed. In absence of a full length complement to a specific target sequence that has been shown to be reliant for the inhibition, the structure would not meet the function. The specification does not adequately describe the structure within the instantly recited genus that is required for each of the recited functions.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
The specification discloses and ASO PMO strand and a fully complementary RNA as the second strand, wherein the ASO PMO is fully complementary to a specific portion of a Dystrophin target sequence that results in exon-skipping, which is a species that is not representative of the entire claimed genus (Table 1).
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for possible double stranded nucleic acid complexes with varying levels of complementarity between each strand and between the antisense strand and the target within the instant enormous genus that would have the required function of an antisense effect. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Response to Arguments
The previous references of the rejection do not apply because the claims have been amended to require full modification with morpholinos in the antisense strand. However, this does not obviate the lack of written description of the claimed genus of agents with an antisense strand that is 8-40 nucleotides in length that can hybridize to any part (i.e. 2 nt) of a target gene or transcription product and a sense strand of any length (i.e. 1000 nt) that has a base sequence of any length (i.e. 2 nt) that is complementary and can anneal to the antisense strand. This is a genus that has not been adequately described by the instant specification. The specification does not adequately describe the structure required for the function.
The specification discloses and ASO PMO strand and a fully complementary RNA as the second strand, wherein the ASO PMO is fully complementary to a specific portion of a Dystrophin target sequence that results in exon-skipping, which is a species that is not representative of the entire claimed genus (Table 1).
Applicant argues that the specification describes an actual reduction to practice of the claimed method. The specification describes a first nucleic acid strand that is a 25-mer "composed entirely of... morpholino nucleic acids," in which all internucleoside bonds are phosphorodiamidate bonds, annealed to a complementary second strand bearing a tocopherol or cholesterol moiety. It is noted that the claims are not limited to the species argued by applicant.
Applicant argues that the complex was administered intraventricularly to mice, and a pronounced antisense effect (exon skipping of the dystrophin transcription product) was measured in the cerebral cortex, hippocampus, cerebellum, brain stem, and striatum. Spec., Example 2 (Results); FIG. 8. Additional intraventricular experiments using the same wholly morpholino first strand with a range of second strands produced the antisense effect in the cerebellum, brain stem, striatum, hippocampus, occipital cortex, and cervical spine. Spec., Example 4 (Results); FIGS. 12-13. These are described tests of the claimed method - intrathecal or intraventricular administration of the recited complex to regulate expression of a target gene or its transcription product in the central nervous system of a subject.
Again, this species of the specification are not representative of the entire claimed genus. The species is of a specific ASO PMO that is targeted to a specific region of a specific Dystrophin target that has been shown to induce exon skipping and a fully complementary RNA strand.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3, 6-12, 20, and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yokota et al. (WO 2014/203518 A1), in view of Eldar-Finkelman (WO 2005/000192 A2), Fletcher et al. (The Journal of Gene Medicine, 2006; 8: 207–216), Astriab-Fisher et al. (Biochemical Pharmacology 68 (2004) 403–407), and Altmann et al. (Biochemical Society Transactions, Volume 24, 1196, 630-637).
Yokota et al. teach: double-stranded antisense nucleic acid complexes that can efficiently alter the processing of RNA in a cell via an antisense effect, and methods for using the same. One method comprises contacting with the cell a double-stranded nucleic acid complex comprising: a first nucleic acid strand annealed to a second nucleic acid strand, wherein: the first nucleic acid strand comprises (i) nucleotides independently selected from natural DNA nucleotides, modified DNA nucleotides, and nucleotide analogs, (ii) no regions that have 4 or more consecutive natural DNA nucleotides, (iii) the total number of natural DNA nucleotides, modified DNA nucleotides, and nucleotide analogs in the first nucleic acid strand is from 8 to 100, and (iv) the first nucleic acid strand is capable of hybridizing to RNA inside of the cell; and the second nucleic acid strand comprises nucleotides independently selected from natural RNA nucleotides, modified RNA nucleotides, and nucleotide analogs (abstract) (claims 20 and 21).
Yokota et al. teach antisense oligomers that are 16 nucleotides in length with a complementary RNA-based strand (page 25). Yokota et al. teaches: Ranges of the length may be 10 to 35 bases, 12 to 25 bases, or 13 to 20 bases. In certain instances, the choice of length generally depends on a balance of the strength of the antisense effect with the specificity of the nucleic acid strand for the target, among other factors such as cost, synthetic yield, and the like.
Yokota et al. teach: The antisense method is a method of selectively altering the expression of a protein that is encoded by a target gene, by introducing into a cell an oligonucleotide (antisense oligonucleotide (ASO)) which is complementary to a partial sequence of the mRNA (sense strand) of a target gene (page 1) (instant claim 1).
Yokota et al. teach: In some other embodiments, the first nucleic acid strand is (i) selected from a morpholino oligonucleotide, a 2'-O-methyl modified oligonucleotide, a 2'-O-(2-methoxyethyl) modified oligonucleotide, or a bridged nucleotide oligonucleotide, (ii) the total number of nucleotides in the first nucleic acid strand is from 8 to 100, and (iv) the first nucleic acid strand is capable of hybridizing to RNA inside of the cell; and the second nucleic acid strand comprises nucleotides independently selected from natural RNA nucleotides, modified RNA nucleotides, and nucleotide analogs (pages 10 and 11) (instant claims 1 and 3).
Therefore, Yokota et al. teach a double-stranded complex comprising a first and second nucleic acid strand, wherein the strands are complementary to each other and the one strand is complementary to mRNA of a target gene, wherein the one strand is a morpholino oligonucleotide and the other strand comprises nucleotide analogs, meeting the instant limitation of claim 3 that the complex does not comprise four consecutive natural ribonucleosides; and the limitation of claim 1 because each nucleotide is a morpholino in the first strand.
Yokota et al. teach: The bonding between the nucleic acid strand and the functional moiety may be direct bonding, or may be indirect bonding mediated by another material. However, in certain embodiments, it is preferable that a functional moiety be directly bonded to the second nucleic acid strand via covalent bonding, ionic bonding, hydrogen bonding or the like, and from the viewpoint that more stable bonding may be obtained, covalent bonding is more preferred (page 20).
Yokota et al. teach: The moiety having a "targeted delivery function" may be, for example, a lipid, from the viewpoint of being capable of delivering the double-stranded nucleic acid complex of certain embodiments to the liver or the like with high specificity and high efficiency. Examples of such a lipid include lipids such as cholesterol and fatty acids (for example, vitamin E (tocopherols, tocotrienols), vitamin A, and vitamin D); lipid-soluble vitamins such as vitamin K (for example, acylcarnitine); intermediate metabolites such as acyl-CoA; glycolipids, glycerides, and derivatives thereof. However, among these, from the viewpoint of having higher safety, in certain embodiments, cholesterol and vitamin E (tocopherols and tocotrienols) are used (page 20) (instant claims 6-8).
Yokota et al. teach that the functional moiety is bonded to the 5’ end of the second strand (page 20 and Figures 6-7) (instant claim 9).
Yokota et al. teaches incorporation of cleavable BNAs, meeting the instant limitation of a cleavable linker (page 15) (instant claim 10).
Yokota et al. teach that the method is for suppressing the expression level of a product. However, it is noted that instant claims 11 and 12 recite intended uses rather than method steps and the intended uses would necessarily flow from the recited method steps.
Yokota et al. does not teach that the method is in the regulation of a target gene is in central nervous system or that delivery is via intrathecal or intraventricular administration.
However, the route of administration is a matter of design choice depending upon the location of the desired target.
Yokota et al. teaches: There are no particular limitations on the preferred form of administration of the composition of some embodiments, and examples thereof include enteral (peroral or the like) or non-enteral administration, more specifically, intravenous administration, intraarterial administration, intraperitoneal administration, subcutaneous administration, intracutaneous administration, tracheobronchial administration, rectal administration, and intramuscular administration, and administration by transfusion.
Yokota et al. teaches: The composition of some embodiments can be used for animals including human beings as subjects. However, there are no particular limitations on the animals excluding human beings, and various domestic animals, domestic fowls, pets, experimental animals and the like can be the subjects of some embodiments.
Yokota et al. teaches: The double-stranded nucleic acid complex can be delivered to a target site with high specificity and high efficiency, and can suppress the expression of a target gene or the level of a transcription product very effectively.
Therefore, when utilizing the method of Yokota et al. to suppress a target in the CNS of a subject, it would have been obvious to select intrathecal or intraventricular administration as a matter of design choice with a reasonable expectation of success given that Yokota et al. teaches that the method does not have any particular limitations on the mode of delivery and that the complex can be delivered to a target site with high specificity and high efficiency, and can suppress the expression of a target gene or the level of a transcription product very effectively.
For example, Eldar-Finkelman teach a method of inhibiting GSK-3 and methods of treating GSK-3 mediated conditions (abstract) via delivery of GSK-3 inhibitors (page 5), wherein the inhibitor can be siRNA or antisense oligonucleotides (page 36).
Eldar-Finkelman teach that GSK-3 can be inhibited with siRNA or antisense oligonucleotides via intraventricular or intrathecal administration (page 30) and that GSK-3 activity is implicated in various central nervous system disorders. the method according to this aspect of the present invention can be used to treat various chronic neurodegenerative diseases such as, but not limited to, Alzheimer's disease, Huntington's disease, Parkinson's disease, AIDS associated dementia, amyotrophic lateral sclerosis (AML) and multiple sclerosis. As is discussed hereinabove, GSK-3 activity has particularly been implicated in the pathogenesis of Alzheimer's disease (pages 10, 28, and 34).
It would have been obvious to practice the method of Yokota et al. wherein the double-stranded nucleic acid complex is targeted to GSK-3 in the CNS via intrathecal or intraventricular delivery because Eldar-Finkelman offers motivation to inhibit GSK-3 in this manner with antisense oligonucleotides or siRNAs for the treatment of CNS diseases.
Fletcher et al. teach that exon skipping of Dystrophin in the mdx mouse after localised and systemic administration of a morpholino antisense oligonucleotide (title, abstract). Fletcher et al. teach that in comparison to other modifications, the stability of the morpholino structural type, and the fact that it can be delivered to muscle in the absence of a delivery reagent, render this compound eminently suitable for consideration for therapeutic exon skipping to address dystrophin mutations (abstract). The morpholino ASO is 25 nucleotides in length. Therefore, this further bolsters the motivation to utilize a fully morpholino modified antisense strand in the instantly recited size range with a reasonable expectation of success.
Fletcher et al. teach that uptake of double-stranded nucleic acids is more efficient than that of single-stranded antisense oligonucleotides (pages 208 and 213) and reference Astriab-Fisher et al. on page 208 for support. Astriab-Fisher et al. teach that antisense oligonucleotides have increased uptake by delivery as double stranded complexes (title). Fletcher et al. teach: The results obtained suggested that double stranded delivery could provide a simple and effective means for enhancing cell uptake of pharmacologically active oligonucleotides (abstract).
Although Yokota et al. teach that the second nucleic acid strand comprises nucleotides independently selected from natural RNA nucleotides, modified RNA nucleotides, and nucleotide analogs (abstract), Yokota et al. does not specifically teach that the modified nucleotides are nucleosides (claims 20 and 21). However, it would have been obvious to utilize ribonucleosides as a matter of design choice because Altmann et al. teach: the data presented in this paper clearly indicate that Z’-O-methoxyethyl- substituted ribonucleosides are a promising new class of building blocks for second-generation antisense oligonucleotides. The increased RNA- binding affinity and superior nuclease resistance of this modification allow a considerable reduction in phosphorothioate content. This should ultimately aid the design of antisense inhibitors of gene expression with improved potency and an enlarged therapeutic window (page 636). Therefore, it would have been an obvious selection for the second strand of Yokota et al. with a reasonable expectation of the benefits taught by Altmann et al.
Response to Arguments
Applicant argues that Yokota does not teach or suggest a fully-morpholino first strand. Although applicant argues that Yokota is not limited to morpholinos by teaching other species, Yokota is not required to only teach the instantly recited modification. Yokota clearly teaches contacting with a cell a double-stranded nucleic acid complex comprising: a first nucleic acid strand annealed to a second nucleic acid strand, wherein: the first nucleic acid strand is a morpholino oligonucleotide (page 10). Additionally, Yokota is not required to exemplify the teaching.
Applicant argues that Yokota's own list of administration forms does not include intrathecal or intraventricular administration. This is why the rejection is under 35 USC 103(a), rather than under 35 USC 102. Yokota is not relied upon for teaching the instant mode of administration.
Applicant argues that "design choice" is a legal conclusion available only in defined circumstances. It "is appropriate where the applicant fails to set forth any reasons why the differences between the claimed invention and the prior art would result in a different function or give unexpected results." In re Chu, 66 F.3d 292, 298-99, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995); see also In re Gal, 980 F.2d 717, 719, 25 USPQ2d 1076, 1077 (Fed. Cir. 1992) (a finding of obvious design choice is precluded where the claimed structure and the function it performs are different from the prior art). Given that the instant claims are not directed to delivery of any specific oligomer that is targeted to any specific target, the claims certainly do fall within the scope of design choice. Certainly if one wants to utilize double-stranded antisense oligomers complexes as taught by Yokota to target a specific target that is in the nervous system, one would have selected intrathecal or intraventricular administration as a matter of design choice.
Although applicant argues what each individual reference does not teach, this is a rejection that utilizes the combination of references under 35 USC 103(a). Eldar-Finkelman was not relied upon for teaching double-stranded nucleic acid complexes with the instant structural features. Eldar-Finkelman is evidence to support design choice by teaching a specific target that would benefit from intraventricular or intrathecal administration of various nucleic acid inhibitors.
Although applicant argues that the Office Action identifies no teaching in either reference that would have motivated a skilled artisan to deliver Yokota's complex into the cerebrospinal fluid, applicant is arguing limitations that are not claimed. Additionally, Eldar-Finkelman teach that GSK-3 can be inhibited with siRNA or antisense oligonucleotides via intraventricular or intrathecal administration (page 30) and that GSK-3 activity is implicated in various central nervous system disorders. Therefore, it would have been obvious to utilize the construct of Yokota wherein the morpholino ASO first strand is fully complementary to a GSK-3 target sequence in a method of delivering the complex via intraventricular or intrathecal administration with a reasonable expectation of inhibition of the target.
Therefore, when utilizing the method of Yokota et al. to suppress a target in the CNS of a subject, it would have been obvious to select intrathecal or intraventricular administration as a matter of design choice with a reasonable expectation of success given that Yokota et al. teaches that the method does not have any particular limitations on the mode of delivery and that the complex can be delivered to a target site with high specificity and high efficiency, and can suppress the expression of a target gene or the level of a transcription product very effectively.
Applicant argues that Yokota does not exemplify a first strand in which 100% of the nucleic acids are morpholino nucleic acids, which is not required. The teachings of Yokota are considered as enabled as the instant specification.
With regards to the unexpected results argued by applicant, the unexpected results are not commensurate in scope with the instant claims.
In the instant specification Example 2, a double-stranded complex having a wholly morpholino first strand and a tocopherol- or cholesterol-conjugated complementary strand was administered by a single intraventricular dose, and produced a "particularly pronounced exon skipping effect" in the cerebral cortex, hippocampus, cerebellum, brain stem, and striatum. Spec., Example 2 (Results); FIG. 8. In Comparative Example 1, by contrast, a complex containing no morpholino nucleic acid - a 16-mer LNA/DNA gapmer annealed to a cholesterol-conjugated complementary RNA strand - was administered intraventricularly, and the specification reports that such "heteroduplex oligonucleotides without morpholino nucleic acid did not show significantly better gene suppression than single-stranded nucleic acid (ASO) not containing morpholino nucleic acid, even when cholesterol was similarly bound to the complementary strand." Spec., Comparative Example 1 (Results); FIG. 9.
The instant claims are not limited to the specific PMO ASO sequence of the specification that is directed to a specific portion of a specific target that results in exon skipping when in a duplex with a fully complementary RNA oligomer.
The comparative complex of Comparative Example 1 is a gapmer first strand annealed to an RNA-based second strand carrying cholesterol as a targeted-delivery functional moiety. Its result is that the benefit obtained upon intraventricular administration is not a property of heteroduplex formation and lipid conjugation as such; it is obtained with a wholly morpholino first nucleic acid strand and is not obtained without one. The specification states as much: "[t]he increase in the effect of intraventricular administration of PMO by heteronucleic acid formation and ligand addition was unexpected considering the fact that, as shown in Comparative Example 1 ..., no increase in the effect of intraventricular administration by heteronucleic acid formation and ligand addition is observed for nucleic acids not containing morpholino nucleic acid." Spec., Example 2 (Results). The specification separately reports that antisense activity from a complex "in which all of the first nucleic acid strand is RNaseH-resistant morpholino nucleic acid" was itself "unexpected, considering the common technical knowledge that a major part of an antisense effect of a double-stranded nucleic acid agent is due to an RNase H-dependent pathway." Spec., Example 1 (Results); FIG. 7. These results are not commensurate in scope with the instant claims that are directed to any double stranded nucleic acid complex with a first strand that is 8-40 nucleotides in length and second strand of any length (i.e. 1000 nucleotides) wherein the first strand comprises a sequence of any length within the 8-40 nucleotides (i.e. 2 nt) that is capable of hybridizing to at least any part of any target gene or any transcription product thereof. The second strand comprises a base sequence of any length (i.e. 3 nucleotides) that are complementary to the first strand, which would result in annealing. The first strand is not necessarily the same length as the second strand and is annealed at any level (i.e. a single nucleotide).
The specification discloses and ASO PMO strand and a fully complementary RNA as the second strand, wherein the ASO PMO is fully complementary to a specific portion of a Dystrophin target sequence that results in exon-skipping, which is a species that is not commensurate in scope with the instant claims (Table 1).
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. 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 re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined 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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3, 6-12, 20, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7, 34-36 and 38-40 of copending Application No. 17/602,035 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of application ‘035 are directed to a method of suppressing or increasing the expression of a transcription product in skeletal or heart muscle via delivery of a double-stranded nucleic acid complex comprising a first nucleic acid strand and a second nucleic acid strand, wherein said first nucleic acid strand comprises a base sequence that is capable of hybridizing to all or part of said transcription product of the target gene, and has an antisense effect on said transcription product, said second nucleic acid strand comprises a base sequence complementary to said first nucleic acid strand, and is bound to cholesterol or analog thereof, and said first nucleic acid strand is annealed to said second nucleic acid strand. The first strand is fully modified with morpholino nucleic acids.
Application ‘035 recites (claim 7) that the nucleic acid consists of sugar-modified nucleosides. Although application ‘035 does not recite that the sugar-modified nucleosides are morpholinos, the specification defines the sugar-modified nucleosides as including morpholinos. The incorporation of at least 2 morpholinos or wherein the double stranded complex does not comprise four consecutive natural ribonucleosides are obvious variations of the claims of application ‘035 which recite full modification with sugar-modified nucleosides. Application ‘035 recites that the nucleic acid does not comprise a natural ribonucleoside (claim 6).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
Prosecution Insights