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
This action is in response to the papers filed January 21, 2026.
Amendments
Applicant's response and amendments, filed January 21, 2026, to the prior Office Action is acknowledged. Applicant has cancelled Claims 2, 4, and 9-10, withdrawn Claim 6, amended Claims 1, 3, 5-8, and 11, and added new claims, Claims 12-17.
Claims 1, 3, 5-8, and 11-17 are pending.
Election/Restrictions
Applicant has elected with traverse the following species:
i) the alternative promoter a DC190 promoter, as recited in Claims 5 and 7; and
ii) the alternative delivery route is bloodstream, as recited in Claim 8.
Claims 1, 3, 5-8, and 11-17 are pending.
Newly submitted Claims 12-13 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: the claims are directed to an alternative, structurally different viral vector special technical feature that would have been set forth in a species election in the Office Action mailed July 30, 2025 had the claims been originally presented.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, Claims 12-13 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims 6 and 12-13 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1, 3, 5, 7-8, 11, and 14-17 are under consideration.
Priority
This application is a 371 of PCT/US2021/039537 filed on June 29, 2021. Applicant’s claim for the benefit of a prior-filed application provisional application 63/046,202 filed on June 30, 2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Claim Objections
1. Claim 7 is objected to because of the following informalities: the word ‘promoter’ (line 2) is misspelled.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
2. The prior rejections of Claims 1-5 and 7-11 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, are withdrawn in light of Applicant’s amendments to the independent Claim 1 to recite:
the subject is human;
the nucleic acid comprises a liver- or hepatocyte-specific promoter operably linked to the nucleic acid encoding acid sphingomyelinase;
the nucleic acid is administered into the liver or bloodstream of the human subject; and
canceling recitation of preventing,
which the Examiner finds persuasive.
Claim Rejections - 35 USC § 102
3. The prior rejection of Claim(s) 1, 4-5, and 7-11 under 35 U.S.C. 102(a)(1) as being anticipated by Barbon et al (AAV8-Mediated Hepatic Expression of Acid Sphingomyelinase Corrects the Metabolic Defect in the Visceral Organs of a Mouse Model of Niemann–Pick Disease, Molecular Therapy 12(3): 431-440, 2005; of record) is withdrawn in light of Applicant’s amendment to independent Claim 1 narrowing the scope to human subjects, a limitation which Barbon et al do not teach.
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 of this title, 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(a) 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.
4. Claims 1, 3, 5, 7-8, 11, and 14-17 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Barbon et al (2005; of record) and in view of Defour et al (available online June 26, 2014; Applicant’s own work; of record in IDS).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Instant specification discloses an embodiment of the claimed subject includes those that have Niemann-Pick Disease (e.g. pg 9, lines 31-33).
Barbon et al is considered relevant prior art for having taught a gene therapy method for the treatment of Niemann-Pick disease in a mouse subject, the method comprising the step of administering to said mouse a nucleic acid encoding Acid Sphingomyelinase. Barbon et al taught wherein the muscular dystrophy mouse model is an ASM knockout mouse (e.g. Abstract).
Barbon et al taught wherein the rAAV-ASM vector was administered intravenously (syn. “injected directly into the bloodstream”) to the mouse (e.g. pg 432, col. 2).
Barbon et al taught wherein the rAAV vector genome comprises a DC190 promoter (syn. “a liver-specific or hepatocyte-specific promoter”) operably linked to the ASM transgene, wherein the ASM transgene encodes a human ASM (e.g. pg 431, col. 2, AAV1/DC190-hASM).
Barbon does not teach wherein the mouse model is deficient for dysferlin (syn. dysferlin knockout) or suffers from a dysferlinopathy, e.g. LGMD2B or Myioshi muscular dystrophy 1.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim(s) 1 and 3, Applicant themselves (Defour et al) is considered relevant prior art for having taught that ASM secretion is reduced in dysferlinopathic cells, e.g. dysferlin knockout cells (e.g. pg 2, col. 1, “dysf-KO”) or LGMD2B myoblasts (e.g. pg 4, col. 2), and that overexpression of ASM restored the ability of dyserlinopathic myoblasts and myofibers to repair cell membranes, providing a mechanism by which ASM is a potential therapy for dysferlinopathy (e.g. Abstract).
Applicant themselves (Defour et al) taught that, in view of their results, “ASM treatment is a therapeutic option that could be evaluated for its clinical efficacy for dysferlinopathic patients (syn. human subject)” (e.g. pg 8, col. 2, Conclusory sentence).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, gene therapy vectors, and muscular dystrophy diseases, disorders, and conditions. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first disease, disorder, or condition characterized by a decrease or loss of acid sphingomyelinase function or activity, e.g. Niemann-Pick disease, as taught by Barbon et al, with a second disease, disorder, or condition characterized by a decrease or loss of acid sphingomyelinase function or activity, e.g. a dysferlinopathy, as taught by Defour et al, in an acid sphingomyelinase gene therapy method with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06.
An artisan would be motivated to substitute a first disease, disorder, or condition characterized by a decrease or loss of acid sphingomyelinase function or activity, e.g. Niemann-Pick disease, with a second disease, disorder, or condition characterized by a decrease or loss of acid sphingomyelinase function or activity, e.g. a dysferlinopathy, in an acid sphingomyelinase gene therapy method because Defour et al taught and successfully demonstrated that ASM secretion is reduced in dysferlinopathic cells, e.g. dysferlin knockout cells or LGMD2B myoblasts, and that overexpression of ASM restored the ability of dyserlinopathic myoblasts and myofibers to repair cell membranes, providing a mechanism by which ASM is a potential therapy for dysferlinopathy.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claims 5 and 7, Barbon et al taught wherein the ASM transgene is operably linked to a DC190 promoter (e.g. pg 431, col. 2).
With respect to Claims 11 and 16, Barbon et al taught wherein the ASM transgene is encoded by an AAV expression vector (e.g. pg 431, col. 2).
With respect to Claims 14-15 and 17, Barbon et al taught wherein the rAAV serotype is AAV8 (e.g. pg 432, col. 2, AAV8/DC190-hASM).
With respect to Claim 8, Barbon et al taught wherein the AAV DC190-hASM vector is administered to the bloodstream (e.g. pg 431, col. 2, “intravenous administration”).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Response to Arguments
Applicant argues that Barbon et al is directed to Neimann-Pick disease, which is not a muscular dystrophy.
Applicant’s argument(s) has been fully considered, but is not persuasive.
The Examiner must determine what is "analogous prior art" for the purpose of analyzing the obviousness of the subject matter at issue. **>"Under the correct analysis, any need or problem known in the field of endeavor at the time of the invention and addressed by the patent [or application at issue] can provide a reason for combining the elements in the manner claimed. " KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). Thus a reference in a field different from that of applicant's endeavor may be reasonably pertinent if it is one which, because of the matter with which it deals, logically would have commended itself to an inventor's attention in considering his or her invention as a whole.<
Barbon et al is considered relevant prior art for having taught a gene therapy method for the treatment of Niemann-Pick disease in a mouse subject, the method comprising the step of administering to said mouse a nucleic acid encoding Acid Sphingomyelinase. Barbon et al taught wherein the rAAV vector genome comprises a DC190 promoter (syn. “a liver-specific or hepatocyte-specific promoter”) operably linked to the ASM transgene, wherein the ASM transgene encodes a human ASM (e.g. pg 431, col. 2, AAV1/DC190-hASM), and wherein the rAAV-ASM vector was administered intravenously (syn. “injected directly into the bloodstream”) to the mouse.
Thus, those of ordinary skill in the art previously recognized and successfully reduced to practice a therapeutic method comprising the intravenous administration of an rAAV virus whose genome encodes a liver-specific or hepatocyte-specific promoter operably linked to a nucleic acid encoding Acid Sphingomyelinase (ASM) to a mammalian subject.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Defour et al (Applicant’s own work) is considered relevant prior art for having taught that ASM secretion is reduced in dysferlinopathic cells, e.g. dysferlin knockout cells (e.g. pg 2, col. 1, “dysf-KO”) or LGMD2B myoblasts (e.g. pg 4, col. 2), and that overexpression of ASM restored the ability of dyserlinopathic myoblasts and myofibers to repair cell membranes, providing a mechanism by which ASM is a potential therapy for dysferlinopathy (e.g. Abstract).
Applicant themselves (Defour et al) taught that, in view of their results, “ASM treatment is a therapeutic option that could be evaluated for its clinical efficacy for dysferlinopathic patients (syn. human subject)” (e.g. pg 8, col. 2, Conclusory sentence).
Applicant argues that the Examiner has not articulated why treating a liver disease is substitutable with treating a dysferlinopathy.
Applicant’s argument(s) has been fully considered, but is not persuasive. Applicant themselves (Defour et al) taught that ASM secretion is reduced in dysferlinopathic cells, e.g. dysferlin knockout cells (e.g. pg 2, col. 1, “dysf-KO”) or LGMD2B myoblasts (e.g. pg 4, col. 2), and that overexpression of ASM restored the ability of dyserlinopathic myoblasts and myofibers to repair cell membranes, providing a mechanism by which ASM is a potential therapy for dysferlinopathy (e.g. Abstract).
Applicant themselves (Defour et al) taught that, in view of their results, “ASM treatment is a therapeutic option that could be evaluated for its clinical efficacy for dysferlinopathic patients (syn. human subject)” (e.g. pg 8, col. 2, Conclusory sentence).
The Examiner notes that Barbon et al taught that the ASM is naturally secreted from cells, and that the secreted proteins are in a form that can facilitate metabolic cross-correction of distal cells (e.g. pg 431, col. 2), and that the rAAV-encoded ASM expressed by the transduced liver cells is detected in blood serum, whereby hepatic secretion of the enzyme into the systemic circulation facilitated its subsequent uptake by other tissues (e.g. pg 432, col. 2).
Those of ordinary skill in the art have long-recognized that it is natural law of anatomy and physiology that muscle tissue comprises the blood circulatory system tissue, and that said blood circulatory system delivers biological compounds to the muscle tissue, as illustrated below:
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Conclusion
5. No claims are allowed.
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 KEVIN K. HILL whose telephone number is (571)272-8036. The examiner can normally be reached 12pm-8pm EST.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638