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 SEQ ID NO: 53, APP, AD-961583, and Alzheimer’s disease in the reply filed on 4/9/26 is acknowledged.
Drawings
The drawings filed on 9/1/23 are objected to because they are not fully legible (Figures 2, 4B, 15C, 17F, 19, 20A, and 22A-C).
The drawings are objected to for the following reasons:
37 C.F.R. 1.84 states “Character of lines, numbers, and letters. All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.”
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Sequence Compliance
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 because there are sequences in the drawings, for example, that do not contain a SEQ ID NO.
A complete response to this office action must correct the defects cited above regarding compliance with the sequence rules and a response to the action on the merits which follows.
The aforementioned instance of failure to comply is not intended as an exhaustive list of all such potential failures to comply in the instant application. Applicants are encouraged to thoroughly review the application to ensure that the entire application is in full compliance with all sequence rules. This requirement will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities: There are structures in the specification that are not fully legible (pages 51, 52, 54-58, 85, 130, 142, and 150).
Appropriate correction is required.
Claim Objections
Claim 8 is objected to because of the following informalities: The claim recites abbreviations for genes. The first recited abbreviation is required to recite the full gene name with the abbreviation in parentheses. Appropriate correction is required.
Improper Markush Rejection
Claims 8, 38, and 71 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are reducing a large genus of target genes, each having a different sequence and no common searchable core. iRNA agents targeted to each of the target genes would have different sequences and therefore different activities that are dependent upon the specific sequence of nucleotides.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, activity of any specific gene or iRNA agent targeting it is dependent upon the specific sequence of nucleotides. There is no expectation that any one of the nucleotide sequences as claimed can be substituted for any of the other with a completely different sequence with the expectation of the same activity.
As set forth in MPEP2117, “Note that where a Markush group includes only materials from a recognized scientific class of equivalent materials or from an art-recognized class, "the mere existence of such a group in an application tend[s] to prove the equivalence of its members and when one of them [is] anticipated the group [is] therefore rendered unpatentable, in the absence of some convincing evidence of some degree of non-equivalency of one or more of the remaining members." In re Ruff, 256 F.2d 590, 598-99, 118 USPQ 340, 348 (CCPA 1958)("[A]ctual equivalence is not enough to justify refusal of a patent on one member of a group when another member is in the prior art. The equivalence must be disclosed in the prior art or be obvious within the terms of Section 103." Id. at 599, 118 USPQ at 348).”
In the instant case, art against any one gene would not be evidence against any of the remaining members that have completely different sequences and do not have identical activity.
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 71 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 71 recites “(e.g., cervical, thoracic, and/or lumbar DRG)”. Reciting “e.g.” in a claim is not permitted because the metes and bounds of the claim are not definite. It is unclear whether the recitation is limiting in any meaningful manner.
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, 2, 4-10, 12, 16, 37, 38, 70, 71, and 109-116 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 claims are directed to methods of delivering iRNA agents of any length (i.e. 1,000 nt in length) that comprise an antisense strand comprising at least 12 (15 differing by no more than 3) from any of the instantly recited sequences and a sense strand complementary to the antisense strand.
The siRNAs of the specification that have a strand that is fully complementary to a specific APP sequence are not representative of the entire claimed genus of iRNA agents of any length that comprise as little as 12 nucleotides in common with one of the instantly recited APP sequences.
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 RNAi agents of any length that comprise 15 contiguous nucleotides of instant SEQ ID NO: 669 in the antisense strand in the same or a different portion than the double-stranded region and have no other sequence specificity to any specific HAO1 target sequence and function by inhibiting the expression of HAO1.
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.
To achieve the desired function, it appears that the structure is required to be of a shorter length than the claimed genus which has no length limitation. With respect to siRNAs, as single species of iRNA agents, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
The claims encompass very long dsRNA, for example, that can trigger RNAi. Such dsRNA with 12 contiguous nucleotides of any of the instantly recited APP sequences would not likely function as claimed. For example, Parrish et al. (Molecular Cell, Vol. 6, 1077–1087, November, 2000) teach that sequences of 1000 bp trigger RNAi (page 1078).
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 iRNA agents within the instant enormous genus that are inhibitory of the target as claimed. 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.
Additionally, the specification does not adequately describe the genus of CNS disorders. Without further description of the genus, one would not be able to readily envision which disorders meet the instant limitation of being CNS disorders; or of being disorders “affecting” the cerebral cortex, hypothalamus, cerebellum, striatum, hippocampus, cerebellum, brain stem, hypothalamus, pituitary, cervical spine, lumbar spine, thoracic spine, trigeminal ganglion, caudate nucleus, pons/medulla, and/or dorsal root ganglion (DRG).
Claims 1, 2, 4-10, 12, 16, 37, 38, 70, 71, and 109-116 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 inhibition of APP via direct delivery of APP siRNAs of the specification, does not reasonably provide enablement for a method of reducing the expression of any target gene or treating any CNS disorder via delivery of the instant genus of iRNA agents; or of treating any CNS disorder with any specific siRNA. 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.
Factors to be considered in a determination of lack of enablement include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The claims are directed to a method of reducing the expression of any target gene or treating any CNS disorder via delivery of the instant genus of iRNA agents that can be of any length (i.e. 1000 nt) and comprise 12 nucleotides of any of the instantly recited sequences; or of treating any CNS disorder via inhibition of APP alone.
It is noted that the sequences recited in claims 1, 37, and 70 are disclosed in the specification as human APP sequences. However, the claims are directed to inhibition of any possible target gene and claims 8, 38, and 71 recite genuses of targets. The specification is not enabling for delivery of iRNA agents that are specific for APP and the reduction of any other target or the genus of recited targets. It would involve undue experimentation to determine which targets are predictably inhibited via inhibition of APP.
The specification demonstrates APP mRNA knockdown with AD-454844 via direct delivery via intracisternal magna injection (Example 2), which is not enabling for a method of reducing the expression of any possible target or any of the targets of claims 8, 38, and 71 other than APP; and is not enabling for a method of treating any possible CNS disorder.
With regards to siRNAs, a single species of iRNA agents, siRNAs with at least 12 contiguous nucleotides of each of the instantly recited APP sequences would not predictably inhibit APP, nonetheless any other target.
For example, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
There are no pending claims limited to the specific siRNAs of the specification that have demonstrated to inhibit APP. With regards to these siRNAs, the specification does not draw an adequate nexus between inhibition of APP alone and the predictable outcome of treating any disorder of the CNS. The specification has not demonstrated even treatment of a single species of CNS disorder via delivery of any specific siRNA targeting APP, encompassing an enormous possible genus of CNS disorders that have not been shown to be reliant upon APP expression alone.
Friedrich et al. (BioDrugs (2022) 36:549–571) teach that still, the development of siRNA therapeutics faces several challenges and issues, including the definition of optimal siRNAs in terms of target, sequence, and chemical modifications, siRNA delivery to its intended site of action, and the absence of unspecific off-target effects (Abstract). Friedrich et al. teach that the use of short siRNA is preferred because longer siRNAs can provoke an inflammatory antiviral immune response (page 551).
Friedrich et al. teach: As a basic parameter, the GC content of an siRNA is addressed by algorithms and its range should be between ~30 and 60%. Too low GC content can lead to weak or unspecific binding, whereas too high GC content may impede unwinding by helicase and incorporation in the RISC complex. Between nucleotides 9 and 14, however, low GC content is important to increase RISC function during mRNA cleavage. Sequences that could lead to secondary structures in the sense or antisense stand must be avoided (e.g., internal repeats, palindromes, CCC or GGG sequences). A proper duplex formation is essential for functional siRNA. Additionally, sequences that contain single nucleotide polymorphisms, miRNA seed matches, and known toxic motifs must be avoided (page 552).
Friedrich et al. teach: The 5′-untranslated region (and 3′-untranslated region) of mRNA as well as sequences close to the start codon are not recommended as siRNA targets, as the binding of regulatory proteins in this area may impede RISC binding and thus the silencing effect. Rather, selecting regions in the open reading frame about 50–100 nucleotides downstream of the start codon is recommended. Furthermore, siRNAs closer to the start codon seem to be more efficient than those further downstream (page 552). Friedrich et al. is evidence as to the delivery challenges, as well as the fact that not any siRNA inhibitor of any length would result in the desired therapeutic effect.
As outlined above, it is well known that there is a high level of unpredictability in the RNAi art for therapeutic in vivo applications and design. The scope of the claims in view of the specification as filed together do not reconcile the unpredictability in the art to enable one of skill in the art to make and/or use the claimed invention, namely a broad method of treating any CNS disorder or inhibiting any gene via delivery of the instant genus of iRNA agents encompassing in vivo effects.
MPEP 2164.01
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Also, MPEP 2164.01(a)
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Given the teachings of the specification as discussed above, one skilled in the art could not predict a priori whether introduction of any iRNA agent of the instant genus in vivo by the methodologies of the instantly claimed invention, would result in successful treatment of any CNS disorder or reduction of any target. To practice the claimed invention, one of skill in the art would have to de novo determine; the stability of the molecule in vivo, specificity to the target tissue in vivo, dosage and toxicity in vivo, and entry of the molecule into the cell in vivo and the effective action therein. 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.
The specification does not demonstrate that delivery of the instantly recited genus of agents to the subarachnoid space would predictably result in reduction in any specific target gene or treatment of any CNS disorder in the cerebral cortex, hypothalamus, cerebellum, striatum, hippocampus, cerebellum, brain stem, hypothalamus, pituitary, cervical spine, lumbar spine, thoracic spine, trigeminal ganglion, caudate nucleus, pons/medulla, and/or dorsal root ganglion (DRG) of a subject
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation (see MPEP 2164.01(a)).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4-6, 8-10, 12, 16, 37, 38, 70, 71, 109-112, 114, and 115 is/are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Milstein et al. (WO 2020/132227 A2).
The reference is of record and cited on the IDS filed on 4/9/26.
Milstein et al. teach: The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting the APP gene, as well as methods of inhibiting expression of an APP gene and methods of treating subjects having an APP-associated disease or disorder, such as cerebral amyloid angiopathy (CAA) and early onset familial Alzheimer disease (EOFAD or eFAD), using such dsRNAi agents and compositions (abstract).
Milstein et al. teach: the double-stranded RNAi agent is delivered by intrathecal injection (i.e. injection into the spinal fluid which bathes the brain and spinal cord tissue). Intrathecal injection of RNAi agents into the spinal fluid can be performed as a bolus injection or via minipumps which can be implanted beneath the skin, providing a regular and constant delivery of siRNA into the spinal fluid. The circulation of the spinal fluid from the choroid plexus, where it is produced, down around the spinal cord and dorsal root ganglia and subsequently up past the cerebellum and over the cortex to the arachnoid granulations, where the fluid can exit the CNS, that, depending upon size, stability, and solubility of the compounds injected, molecules delivered intrathecally could hit targets throughout the entire CNS (instant claims 6, 37, and 38).
Milstein et al. teach that the iRNA agent can be delivered via intrathecal administration via a pump. The pump may be a surgically implanted osmotic pump. In one embodiment, the osmotic pump is implanted into the subarachnoid space of the spinal canal to facilitate intrathecal administration (instant claims 1, 37, and 38).
Milstein et al. teach: In one embodiment, the double-stranded RNAi agent is administered intrathecally. By intrathecal administration of the double-stranded RNAi agent, the method can reduce the expression of an APP target gene in a brain or spine tissue, for instance, cortex, cerebellum, striatum, cervical spine, lumbar spine, and thoracic spine.
Milstein et al. teach that the RNAi agent comprises a lipophilic moiety conjugated to one or more internal positions (claim 3).
Milstein et al. teach that the RNAi agent is AD-454844, AD-961583, AD-961584, AD-961585, AD-961586 (claim 5), which comprises instant SEQ ID NOs: 39, 41, 42, 44 (AD-454844 and AD-994379 in Figure 21A) and 53-56 (AD-961583, AD-961584, AD-961585, AD-961586) (instant claims 1, 8, 109, 111, and 114; Figures 21A-21B).
Milstein et al. teaches that the lipophilicity of the lipophilic moiety, measured by logKow, exceeds 0 (claim 8) (instant claim 2); and the hydrophobicity of the double-stranded RNAi agent, measured by the unbound fraction in the plasma protein binding assay of the double-stranded RNAi agent, exceeds 0.2 (claim 9)(instant claim 2).
Milstein et al. teach: the plasma protein binding assay is an electrophoretic mobility shift assay using human serum albumin protein (claim 10)(instant claim 4).
Milstein et al. teach: the lipophilic moiety contains a saturated or unsaturated C16 hydrocarbon chain (claim 46)(instant claim 5).
Instant claims 9, 10, 12, 16, 38, 71, recite outcomes that would necessarily flow from the method of Milstein et al. Milstein et al. teach each of the recited method steps and therefore would necessarily achieve each of the instantly recited outcomes. It is noted that outcomes are recited by Milstein et al. (claim 139).
Milstein et al. teach: Exemplary CNS disorders that can be treated by the method of the disclosure include Alzheimer, amyotrophic lateral sclerosis (ALS), frontotemporal dementia, Huntington, Parkinson, spinocerebellar, prion, and Lafora (claims 133-138) (instant claims 70 and 71).
Milstein et al. teach that the lipophilic moiety can be conjugated via a linker or carrier (claim 3) (instant claims 110, 112, and 115).
Milstein et al. teach the instantly recited duplexes and modifications (Figures 21A and 21B).
Therefore, the claims are anticipated by Milstein et al.
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) 7, 113, and 116 is/are rejected under 35 U.S.C. 103 as being unpatentable over Milstein et al. (WO 2020/132227 A2), as applied to claims 1, 2, 4-6, 8-10, 12, 16, 37, 38, 70, 71, 109-112, 114, and 115 above, and further in view of DeMattos et al. (PNAS, 2001, 98, 15, 8850-8855), and Nair et al. (WO 2020/257194 A1).
The Milstein et al reference is of record and cited on the IDS filed on 4/9/26. . The Nair et al. reference is of record and cited on the IDS filed on 9/1/23.
Milstein et al. do not teach that the subarachnoid space is the cisterna magna. However, given that Milstein et al. teaches that the iRNA agent can be delivered via intrathecal administration for treatment of Alzheimer’s disease via a pump and that the pump may be a surgically implanted into the subarachnoid space of the spinal canal to facilitate intrathecal administration, it was known to implant a pump that injects siRNA targeting APP into the subarachnoid space. Selection of the cisterna magna would have been an obvious selection because it was known to inject drugs into the cisterna magna for the treatment of Alzheimer’s disease, as taught by DeMattos et al.
Therefore, since it was known to inject Alzheimer’s therapeutics into the cisterna magna, it would have been obvious to select the cisterna magna for the therapeutic of Milstein et al. with a reasonable expectation of inhibition of APP.
Additionally, Nair et al. teach that the cerebrospinal fluid fills the subarachnoid space-a gap between two of the membranes that encase the brain and spinal cord—as well as the ventricles of the brain, cisterns, sulci, and the central canal of the spinal cord. Intrathecal injections into the spinal canal or subarachnoid space are known to reach the CSF [00216]. Since Milstein et al. teaches injection into the spinal fluid that bathes the brain and spinal cord tissue, the method of Milstein et al. would be expected to reach various areas of the subarachnoid space.
Conclusion
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
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