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 Application/Amendment/Claims
Applicant's response filed 02/10/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 11/19/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 02/10/2026, claims 1-10, 12-15 and 18-21 are pending. Claims 1-10, 12-13 and 18-21 are currently under examination. Claims 14 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejection not reiterated in this Office Action is hereby withdrawn.
New Claim Rejections
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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-5, 8, 9, 12, 13 and 18-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Uchino et al. ("SHANK3 as an autism spectrum disorder-associated gene." Brain and Development 35.2 (2013): 106-110 of record), Monteiro et al. ("SHANK proteins: roles at the synapse and in autism spectrum disorder." Nature Reviews Neuroscience 18.3 (2017): 147-157 of record), WO 2017106382 (WO ‘382 of record in IDS filed 10/24/2022), Choi et al. (Molecular Brain 2015 1-12) and Zhang et al. ("Antisense technology." Cancer Gene Therapy. Totowa, NJ: Humana Press, 2005. 35-49 of record).
Claim interpretations:
The claims recite the phrase “essentially complementary to” or “essentially identical to” and is defined in the specification as meaning 100% complementary or identical to the sequence.
Claim 1 is drawn to an oligonucleotide at least 10 continuous bases complementary to SEQ ID No. 1 and is interpreted such that an oligonucleotide can have a maximum of 10 nucleotides in length and can also be any length greater than 10 nucleotides of SEQ ID No. 1.
Regarding claims 1 and 2, Uchino et al. teach Shank3 is an autism spectrum disorder-associated (ASD) gene that causes a developmental disorder, 22q13.3 deletion syndrome known as Phelan–McDermid syndrome (PMDS), that is characterized by severe expressive language and speech delay, hypotonia, global developmental delay, and autistic behavior (see abstract). Uchino et al. teach mutations in the Shank3 gene have been identified and found such mutations in autistic patients (see page 107 section 4). Uchino et al. teach these mutations are predicted to cause a frameshift and result in production of an aberrant truncated SHANK3 protein (see page 107 first para).
Regarding claims 1 and 2, Monteiro et al. also teach Shank3 mutations are associated with ASD (see page 147 second col.) and teach patients with Shank3 mutations have more severe cognitive deficits (see page 150 col. 1). Monteiro et al. found several behavioral abnormalities have been reported in mice with deletions in Shank3 genes and observed a reversal of these abnormalities when expression was restored (see page 152 col. 2 page 154 first col.). Monteiro et al. teach these studies suggest that adult restoration of SHANK3 levels or restoration of downstream mediators may be a useful approach to alleviate some of the synaptic and behavioral impairments that are associated with SHANK3 mutations (see last para. page 155).
Regarding claims 3-5, 8, 9, 12, 13 and 18-21, the reference WO ‘382 teach using antisense oligonucleotides targeted to mRNAs, such as Shank3, increased expression of mRNAs deficient in neurological diseases such as SHANK3 (0009). WO ‘382 teach using antisense oligonucleotides that can be 8 to 50 nucleotides in length and further teach the oligonucleotides can be in a pharmaceutical composition (0010-0011, 0444). WO ‘382 teach the antisense can be delivered in an expression construct (0452) and can be delivered to a host cell ex vivo (0455). WO ‘382 teach making antisense oligonucleotides to a target region and screening by performing an antisense sequence walk to identify specific sequences to a target (0460).
WO ‘382 demonstrates the feasibility of using antisense oligonucleotides targeted to SHANK3 mRNA in subjects having neurological diseases to increase expression of SHANK3 but does not teach targeting SEQ ID No. 1 which is in the 3’UTR region (as stated by Applicant in remarks filed 02/10/2026 page 12).
Choi et al. teach post-transcriptional regulation of SHANK3 expression is by three miRNAs such as miR-7, miR-34a and miR-504 (abstract), which have binding sites in human SHANK 3’UTR (page 2 col. 2 para 1). Choi et al. demonstrates expression of miRNA decreases luciferase activity of constructs of SHANK 3’UTR in cells (page 2 col. 2 para 2). Choi et al. teach there ae at least 10 SHANK3 isoforms and the results suggest that the region having the three miRNAs above in the 3’ UTR can regulate at least six of the known 10 isoforms (see page 7 para 2).
Regarding the limitation of antisense oligonucleotides having at least 10 nucleotides complementary to SEQ ID No. 1 or to SEQ ID Nos. 2 and 3, Zhang et al. also teach there are well known reliable approaches to select an optimal antisense sequence, having 15-25 nt in length, such as sequence-walking which has yielded good results or computer aided selection which allows antisense to be designed to specific target regions predicted to be free from intramolecular base pairing (see page 40). Zhang et al. teach the use of antisense DNA which are used more frequently than RNA (see page 38 2.1.2).
SEQ ID No. 1 is a 1900 nucleotide sequence that represents the chromosome 22 region of Shank3 with the known accession NM_0013720044.1 of chromosome 22 of the full length sequence (Homo sapiens SH3 and multiple ankyrin repeat domains 3 (See NCB1 Blast search). It would have been obvious to one of ordinary skill in the art to make antisense oligonucleotides targeted to SEQ ID No. 1 or targeted to SEQ ID Nos. 2 or 3 (which are within SEQ ID No. 1) to find a complementary oligonucleotide sequence for use in methods of targeting Shank3.
Because Uchino et al. and Monteiro et al. teach ASD is caused by Shank3 mutations that lead to deficiency in the protein, one of ordinary skill in the art would have looked to methods of enhancing production of the Shank3 protein, which is taught by WO ‘382. Further because Choi et al. identified sequences in the 3’UTR region that controlled SHANK3 expression in a majority of the isoforms, one of ordinary skill in the art would have been motivated and capable of making antisense oligonucleotides to this region to increase the expression of SHANK3 to increase the expression, particularly given both WO ‘382 and Zhang et al. teach how to make antisense oligonucleotides to a target region.
In KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court held that "obvious to try" was a valid rationale for an obviousness finding, for example, when there is a "design need" or "market demand" and there are a "finite number" of solutions. 550 U.S. at 421 ("The same constricted analysis led the Court of Appeals to conclude, in error, that a patent claim cannot be proved obvious merely by showing that the combination of elements was ‘[o]bvious to try.’ ... When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under §103."). Thus, after KSR, the presence of a known result-effective variable would be one, but not the only, motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
The prior art teach a need to treat neurological diseases caused by decreased expression of SHANK3, WO ‘382 demonstrates making and using antisense oligonucleotides targeted to a region of a SHANK3 gene which increased expression and Choi et al. identified a region in the 3’ UTR that also showed post-transcriptional regulation of SHANK3 expression. The prior art also teach a finite number of identified and predictable solutions of making and using an antisense oligonucleotide to target a region of the SHANK3 to increase expression which is a known result-effective variable that provides motivation for a person of ordinary skill in the art to experiment to reach another workable product or process
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Response to Applicant’s Arguments
Applicant argues Zhang et al. teach methods of designing oligonucleotides to decrease gene expression which is the opposite of the instant claims to increase expression of SHANK3. This argument is not convincing. Whether the antisense oligonucleotide binds to a target to decrease or increase the expression does not persuade one of the skill in the art to look for efficient and known methods of making an antisense oligonucleotide to a target gene. Zhang et al. teach well known methods of making antisense oligonucleotides targeted to a gene and one of skill in the art would have relied on these methods to make the claim antisense oligonucleotide. As stated above, the method of Zhang et al. and methods taught by WO ‘382 both describe making antisense oligonucleotides using sequence walking to find an optimal sequence that binds and targets the gene and WO ‘382 is using this method to target a gene to increase gene expression. Thus Zhang et al. does in fact provide a teaching and a motivation to use their methods.
Applicant argues WO ‘382 teach a fundamentally different mechanism because it is targeted to an intron 16 of SHANK3 that corrects aberrant splicing, targets a pre-mRNA and increases spliced transcripts. These arguments are not persuasive. WO ‘382 is relied upon in the new 103 rejection for demonstrating it is feasible to make an antisense oligonucleotide to target a SHANK3 gene to increase the expression of the gene. The limitations of “3’UTR” and “Stabilized mature mRNA to prevent degradation” and “Increases half-life of existing mRNA” are not claimed and do not have to be taught by the prior art references. However, given the new 103 rejection above, there is motivation to target the 3’UTR and target mRNA. The limitations of preventing degradation and increasing half-life would be considered inherent features of targeting the mRNA and increasing expression of SHANK3.
Applicant argues the prior art references are internally contradictory because Uchino and Monteiro establish that increased SHANK3 expression is therapeutic but Zhang et al teach inhibiting expression of a gene to decrease expression. This is not persuasive as stated above regarding Zhang et al. and therefore the prior art references are not internally contradictory because Zhang et al. teach making an antisense oligonucleotide that binds to a target sequence.
Applicant argues there is no reasonable expectation of success because Zhang et al. teach the unpredictability of antisense design and this is not a finite number of identified, predictable solutions and teach only a 5% are found to be effective. Applicant further argue one of ordinary skill in the art would not predict which oligonucleotides would increase versus decrease expression and predict mRNA stabilization mechanism. In response, while Zhang et al. teach finding 5% of identified oligonucleotides as effective, Zhang et al. still teach the method has yielded good results. As stated above, the prior art teach a need to treat neurological diseases caused by decreased expression of SHANK3, WO ‘382 demonstrates making and using antisense oligonucleotides targeted to a region of a SHANK3 gene which increased expression and Choi et al. identified a region in the 3’ UTR that also showed post-transcriptional regulation of SHANK3 expression. The prior art also teach a finite number of identified and predictable solutions of making and using an antisense oligonucleotide to target a region of the SHANK3 to increase expression which is a known result-effective variable that provides motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
Applicant further argues the previous 112(a) and 103 are mutually exclusive because it cannot be said that one skilled in the art would have been able to identify oligonucleotides having at least 10 contiguous nucleotides complementary to SEQ ID No. 1 and also the specification and claims do not describe oligonucleotides at least 10 contiguous nucleotides complementary to SEQ ID No. 1. In response, the 103 rejection makes it obvious to make oligonucleotides within optimal ranges such as 15-25 nucleotides as in the prior art references, that would include the claim limitations and the 112(a) rejection above it based on the specification not adequately describing smaller and larger oligonucleotides encompassed by claim 1.
Applicant argues unexpected results support non-obviousness because the results show the claimed oligonucleotides increase SHANK3 protein expression with statistical significance which is the opposite effect in Zhang et al. As argued above, Zhang et al. was and is relied upon to teach methods of making antisense oligonucleotides, which are identical in sequence and function of binding to a target sequence. Applicant’s argument that the oligonucleotides targeting the 3’ UTR stabilize mRNA is not claimed and this argument and that the invention to increase protein expression, as described in the 103 above, would have been expected based on the new 103 rejection above and therefore is not an unexpected result.
Applicant further argues the rejection constitutes impermissible hindsight reconstruction. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). As explained in the 103 rejection above, the prior art teach a need to treat neurological diseases caused by decreased expression of SHANK3, WO ‘382 demonstrates making and using antisense oligonucleotides targeted to a region of a SHANK3 gene which increased expression and Choi et al. identified a region in the 3’ UTR that also showed post-transcriptional regulation of SHANK3 expression. The prior art also teach a finite number of identified and predictable solutions of making and using an antisense oligonucleotide to target a region of the SHANK3 to increase expression which is a known result-effective variable that provides motivation for a person of ordinary skill in the art to experiment to reach another workable product or process.
Lastly Applicant argues acknowledgement that SEQ ID Nos. 4-17 are free of the prior art undermines the rejection. This is not persuasive. There is nothing in the prior art that specifically teach these exact sequences however it would have been obvious to make any other sequence, as broadly claimed, targeted to the 3’ UTR of SHANK3 in efforts to treat a SHANK3 deficiency as described above in the 103 rejection.
Therefore, Applicant’s arguments are not sufficient to overcome the rejections.
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.
Written Description
Claims 1, 2, 8, 9, 12, 13 and 18-21 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
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 claims are drawn to a genus of antisense oligonucleotides at least 10 nucleotides complementary to SEQ ID No. 1 with the function of treating a Shank3 deficiency such as PMDS.
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 specification describes antisense oligonucleotides 50 nt length that were capable of affecting expression of Shank3 in vitro and describes antisense oligonucleotides 18 nt in length that were capable of affecting Shank3 expression in motoneurons (Fig. 1 and 4). The specification and claims do not indicate what distinguishing characteristics of the 18 or 50 nucleotide described in the specification that are concisely shared by the members of the broad genus of dsRNA 10 nucleotides in length that would convey to one of skill in the art that these dsRNA represent the entire genus of oligonucleotides 10 nucleotides in length.
The prior art of Stein ("The experimental use of antisense oligonucleotides: a guide for the perplexed." The Journal of clinical investigation 108.5 (2001): 641-644) teach there can be limits on oligonucleotide specificity and the length of an antisense oligonucleotide must be optimized because with lengths that are too long or too short, specificity is lost and further states the optimal length is roughly 16-20 nucleotides. This loss of specificity is seen if the oligonucleotide is too short or too long (see page 641 col. 2).
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 of oligonucleotides at least 10 nucleotides complementary to SEQ ID No. 1 from the non-functional members without empirical determination. Thus the specification does not describe a representative number of species of the genus of oligonucleotides as claimed with the functional characteristics of targeting a Shank3 gene to treat a Shank3 deficiency.
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 comprising numerous sizes of oligonucleotides with varying degrees of complementarity or identity to the claimed 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.
“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).
"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).
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 one of skill at the time of the invention could not have concluded that Applicant was in possession of the genus of oligonucleotides as claimed.
Claim Rejections - 35 USC § 112
Enablement
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 1, 2, 8, 9, 12, 13 and 18-20 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 methods of modulating Shank3 expression in cells using antisense oligonucleotides 18 and 50 nucleotides,
does not reasonably provide enablement for methods of treatment Shank3 deficiency in a subject using an oligonucleotide having at least 10 nucleotides complementary to SEQ ID No. 1.
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 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 claims are drawn to methods of treating a Shank3 deficiency, such as PMDS, comprising contacting the subject with an oligonucleotide at least 10 nucleotides complementary to SEQ ID No. 1. Thus the nature of the invention relies upon using any size oligonucleotide comprising at least 10 nucleotides in length that is capable of treating any Shank3 deficiency or PMDS.
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:
A thorough review of the patent and non-patent literature indicates that the state of the art as providing a correlation between Shank3 deficiency and autism spectrum disorder-associated (ASD) (see Uchino et al. and Monteiro et al. above in the 103 rejection). The state of the art also teach methods of generating antisense oligonucleotides, 18 nt in length (0009), to enhance production of correctly spliced mRNAs deficient in neurological diseases, such as Shank3 and teach the Genbank sequence of Shank3 as NM_033517 (see Table on pp. 56, 0351-0354 WO ‘382 cited above in the 103 rejection) and teach the oligonucleotides can be used in the treatment of PMDS (see e.g. page 2) (WO ‘382 cited above in the 103 rejection).
The prior art of Stein ("The experimental use of antisense oligonucleotides: a guide for the perplexed." The Journal of clinical investigation 108.5 (2001): 641-644) teach there can be limits on oligonucleotide specificity and the length of an antisense oligonucleotide must be optimized because with lengths that are too long or too short, specificity is lost and further states the optimal length of an antisense oligonucleotides is roughly 16-20 nucleotides (see page 641 col. 2).
A review of the prior art, while demonstrating methods of treatment of a Shank3 deficiency using antisense oligonucleotides 18 nucleotides in length can repair normal Shank3 expression which can lead to treatment of ASD, does not demonstrate use of any sized oligonucleotide at least 10 oligonucleotides targeted to the Shank3 gene, as claimed, that can treat Shank3 deficiency in a subject.
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 for using any sized oligonucleotide to treat Shank3 deficiency 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 Shank3 deficiency in a subject can occur by administering to the subject an oligonucleotide as claimed, 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). One of skill in the art would not be able to predict that any sized oligonucleotide having 10 to100 nucleotides complementary or identical to the claimed sequences would treat a Shank3 deficiency by using the knowledge in the prior art.
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 prior art gives guidance using 18nt antisense oligonucleotides that can target Shank3 but little is known in the art regarding treating a Shank3 deficiency using the breadth of oligonucleotides claimed and one would need more guidance from the application on how to make and use the invention.
The existence of working examples:
The working embodiment in the instant application describes using oligonucleotides 18 nt or 50 nt that modulate Shank3 expression in cells. The working embodiments do not describe making and using any sized oligonucleotide at least 10 oligonucleotides as claimed that would be capable of treating Shank3 deficiency in a subject.
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 using any sized oligonucleotide from 10 to 100 nucleotides complementary to the target gene that would treat Shank3 deficiency in a subject 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:
Neither the prior art nor the specification provides sufficient guidance on predictably using the claimed sized oligonucleotides that would treat Shank3 deficiency. 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.
Claim Objects and Allowable subject matter
SEQ ID Nos. 4-17 are free of the prior art. The prior art does not teach oligonucleotides comprising or consisting of the claimed sequences. Claims 6, 7 and 10 are therefore objected to for being dependent on a rejected claim but would be allowable if rewritten in independent form including all the limitations of the base claims.
The specification discloses the sequences are 18 and 50 nucleotides in length targeted to a Shank3 gene and Genbank NM_0013720044.1 of chromosome 22 is known. The prior art of WO ‘382 teach methods of generating antisense oligonucleotides (0009), to enhance production of correctly spliced mRNAs deficient in neurological diseases, such as Shank3. WO ‘382 do not specifically teach making any of the claimed sequences having 18 or 50 nucleotides in length. While one of skill in the art may be capable of making antisense oligonucleotides to a region of a target gene, there is nothing in the prior art to lead a skilled artisan to make the specifically claimed oligonucleotide sequences of 18 and 50 nucleotides in length.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights