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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/06/2026 has been entered.
Claim Status
Amended claims 1, 3, 16-18, 33, 40, 43-44, 46, 48, 50-54, and new claim 55 are pending and are examined here.
Priority
Claim of benefit of provisional application 62/699,923, filed on 07/18/2018, via the PCT/US2019/042205, filed on 07/17/2019, is recognized. All the examined claims enjoy the benefit of ‘923, with filing date 07/18/2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/06/26 was filed before the mailing date of this Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
35 U.S.C. 112(b)
Rejection of cl. 51-52 under 112(b) is withdrawn since “about” is deleted in the claims.
35 U.S.C. 112(a)
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 and its dependent claims 3, 16-18, 33, 40, 43-44, 46, 48, 50-55 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 the method decreases neurocognitive decline in the human subject and/or reduces a level of glycosaminoglycan (GAG) in a biological sample obtained from the human subject as compared to a level of GAG in a biological sample obtained from the human subject before administration of the rAAV , does not reasonably provide enablement for “the method prevents … neurocognitive decline in the human subject”. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
It should be made clear that, the enabling specification must teach those skilled in the art to make and use the full scope of the claimed invention without undue experimentation. “Although not explicitly stated in section 112, to be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without "undue experimentation." Vaeck, 947 F.2d at 495, 20 USPQ2d at 1444; Wands, 858 F.2d at 736-37, 8 USPQ2d at 1404; In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (the first paragraph of section 112 requires that the scope of protection sought in a claim bear a reasonable correlation to the scope of enablement provided by the specification).” In re Wright (CAFC) 27 USPQ2d 1510 at 1513. Although a working example is not required to enable an invention, the skilled artisan must be able to practice the claimed invention without undue experimentation. See also, MPEP §2164.02, which states in part: 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). Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
Claim 1 explicitly encompass preventing neurocognitive decline in a human subject. Looking to the prior art for guidance, a search of the prior art did not identify any methods which effectively prevents neurocognitive decline in a human subject. The specification also does not provide any working example demonstrating prevention of neurocognitive decline in a human subject. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the specification with respect to preventing neurocognitive decline in a human subject, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful prevention of neurocognitive decline in a human subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
Furthermore, in In re Vaeck, 947 F.2d 488,495, 20 USPQ2d 1438, 1444 (Fed. Cir. 1991), the Court ruled that a rejection under 35 U.S.C. 112, first paragraph for lack of enablement was appropriate given the relatively incomplete understanding in the biotechnological field involved, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims. Such is the case here, where there is a relatively incomplete understanding in the biotechnological field involved, as described above, and the lack of a reasonable correlation between the narrow disclosure in the specification and the broad scope of protection sought in the claims.
Therefore, it is appropriate to reject the claims under 35 USC 112(a) for not being enabled to their full scope. It is noted that amending the claims to, for example, a method of treating neurocognitive decline in a human subject in need thereof (i.e., remove “prevents” from the claims), would obviate this rejection.
Claim Rejections - 35 USC § 103
Rejection of claims 1, 3, 16, 18, 33, 40, 43, 44, 46, 48, 50, 51-54 is maintained and new claim 55 is rejected as noted below.
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.
Claims 1, 3, 16, 18, 33, 40, 43, 44, 46, 48, 50, 51-54 are rejected under 35 U.S.C. 103 as obvious over Hinderer et al. (WO2017136500A1, pub. 08/10/2017, in IDS, referred as Hinderer) and as evidenced by Salvetti et al. (1995, Human Gene Ther., 6, 1153-1159, referred as Salvetti) for cl. 1, and further in view of Mahan (2014, International J. of Clinical Med., 5, pg. 1374-1383) and Kaplitt et al. (2007, Lancet, 369, 2097-2105).
Regarding claims 1, 51, 52, claim 1 is interpreted to encompass the active/positive step of administering a single dose of a recombinant expression vector encoding rIDUA to the human subject diagnosed with MPS I, with the dose based on average brain mass of human subject and age group, while the “wherein the rIDUA is produced by human neuronal cells or human glial cells after the single dose is administered to the human subject” is an inherent property of the recombinant expression vector encoding the protein of interest to express the protein in the target cells.
Hinderer discloses using a recombinant adeno-associated virus (rAAV) to deliver a human alpha-L-iduronidase (IDUA) gene to the CNS of patients (human subjects) diagnosed with MPS I (pg. 3, line 24-26); discloses genome copy dosage based on brain mass of the age of human subject (pg. 4, line 18-29); demonstrates rIDUA activity following treatment with rIDUA-AAV in cerebral spinal fluid (CSF) (pg. 7, line 30 – pg. 8, line 5), thus disclosing the expression vector expressing the recombinant protein in the brain, which is composed of both neuronal and glial cells; discloses that an advantage of gene therapy is successful with a single dose, including in infant macaques (pg. 6, line 15-20). Hinderer discloses the expression level of alpha-L-iduronidase driven from rAAV vector is at least 2% of normal levels as detected in neurons (pg. 14, line 13-20) and also notes that histopathology demonstrated robust transduction of spinal motor neurons in experimental studies of dogs (pg. 70, line 26-27; also pg. 6, line 31 “transgene expressed in motor and sensory neurons”.) Hinderer also demonstrated intrathecal administration of AAV9-mediated gene transfer allowed long term expression of IDUA in brain (pg. 81, line 24-25). Thus Hinderer discloses the expression of the recombinant protein following administration of rAAV-IDUA to the human subject.
Regarding the limitation of “a glycosylated recombinant IDUA of between 76 kDa to 82 kDa as measured by polyacrylamide gel electrophoresis.” Hinderer discloses administering rhesus monkeys with AAV8 vector expressing human IDUA intrathecally, which resulted in increase of serum IDUA activity (pg. 63, lines 13-20). Thus, suggesting that following production in the nervous system that the enzyme was secreted (see also pg. 64, “the widespread reduction in storage pathology observed was due to cross-correction by secreted enzyme” line 12-13). Salvetti indicates that there are various isoforms of the hIDUA protein following production, a 75 kDa, a 72 kDa, a 69 kDa species and indicates that the 72 kDa and 69 kDa corresponds to the catalytically active components of hIDUA following proteolytic processing of a 75-kDa precursor (pg. 1155). However, Salvetti also indicates that the secreted hIDUA species is a 76-kDa phosphorylated on mannose residues that it can be internalized by cells and processed to the characteristics intracellular forms (pg. 1156). Thus, there is a secreted isoform of hIDUA that is 76 kDa. Thus, Hinderer’s hIDUA is also secreted and it’s SEQ ID NO: 2 hIDUA has predicted MW is 72.7 kDa. And as evidenced by Salvetti, one of hIDUA’s processed isoforms is a 76 kDa, which would also migrate at 76 kDa on a polyacrylamide gel.
Hinderer discloses that rAAV “should have a tropism for the CNS (e.g. an rAAV bearing an AAV9 capsid)” (pg. 3, line 27).
Hinderer discloses methods for “treating, and/or ameliorating neurocognitive decline in patient diagnosed with MPS 1” by delivering a therapeutically effective amount of a rAAV hIDUA (pg. 29, line 21-24, relevant to instant cl. 1).
Hinderer does not disclose the exact range of 1×1010 to 5×1010 GC/g brain mass or of 1×1010 or of 5×1010 GC/g brain mass.
Regarding the single dose is between 1×1010 to 5×1010 GC/g brain mass or of 1×1010 or of 5×1010 GC/g brain mass (10 bill. to 50 bill. GC/g; relevant to instant cl. 1, 51, 52), Hinderer discloses the following on pg. 4, a therapeutically effective intrathecal dose range is effectively from 1 billion to 500 billion GC/g brain mass of a patient (see line 19-20).
MPEP 2144.05 provides “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.
Here, in some age groups, the instant claims lie inside the ranges disclosed in Hinderer, thus a prima facie case of obviousness exist.
Second, under MPEP 2144.05(II) provides that “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. ‘[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.’”
Here, the differences are of concentration (GC/g of brain mass or flat GC doses) but lacks evidence indicating that such narrower concentration range or the specific dose is critical. The instant specification provides suggestion or guidance of dosage that “may be used to treat human subject” (par. 322). Similarly, Hinderer also provides “monitoring and adjusting MPSI therapy” (pg. 38, line 9-10) by assessing IDUA activity.
Third, it is well known in the art that one of the necessary purposes of the different phases of clinical trials is to identify optimal dosage by balancing the therapeutic activity and the side effects (Mahan, Table 1, pg. 1375). Kaplitt et al. (2007, Lancet, 369, 2097-2105) discloses during Phase I of a clinical trial of genetic therapy with AAV that three different doses were administered to patients with Parkinson’s disease (1×1011 viral genome (vg)/ml; 3×1011 vg/ml; 1×1012 vg/ml; vg=GC).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified dose ranges of Hinderer and arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to modify the dose ranges for multiple reasons, including patient outcome profile as determined by a physician as taught by Hinderer to provide for reasonable expectation of success in identifying a narrower set of dose ranges for the age groups or dosage based on brain mass. Thus, instant claims 1, 51-52 is obvious.
Regarding instant Claim 3, Hinderer discloses that as a precautionary matter that an immunosuppressive therapy is recommended for all recipients of rAAV-hIDUA (pg. 6, line 2-3); discloses immunosuppressive therapy may be given in addition to the vector, before, during and/or subsequence to vector administration (pg. 42, line 10).
Regarding instant claim 16, 54, Hinderer discloses various drugs for immunosuppression, including prednisolone (a corticosteroid, see par. 23 of instant pub.); sirolimus (i.e. rapamycin) (pg. 32, line 15) and tacrolimus (pg. 32, line 21); and may involve co-administration of two or more drugs (pg. 32, line 24). Hinderer discloses immunosuppressive therapy to include mycophenolate mofetil (MMF), prednisolone, tacrolimus and sirolimus (pg. 42, line 11-13).
Regarding instant Claim 18, Hinderer discloses SEQ ID NO: 2 (claims 5 and 33; and pg. 15, line 25-30), which is 100% identical to instant SEQ ID NO: 1 (alignment is provided below, prior to Conclusion).
Regarding instant Claim 33, Hinderer discloses treating new born to 36 month of age human subject (pg. 4).
Regarding instant Claim 40, Hinderer discloses the expression vector driven by a CB7 promoter, a hybrid between a CMV immediate early enhancer and the chicken beta actin promoter (pg. 3, line 30; pg. 22, line 22-24).
Regarding instant Claim 43, Hinderer discloses that rAAV “should have a tropism for the CNS (e.g. an rAAV bearing an AAV9 capsid) (pg. 3, line 27).
Regarding instant Claim 50, Hinderer discloses administration of AAV-hIDUA via intrathecal/intracisternal injection (pg. 6, line 10-11).
Regarding instant cl. 44, 46, and 48, and 53
Hinderer discloses the following on pg. 4:
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Hinderer discloses age range of 3-36 months regarding the rAAV-hIDUA dosage for MPS I patients.
MPEP 2131.03(II) provides the following:
When the prior art discloses a range which touches or overlaps the claimed range, but no specific examples falling within the claimed range are disclosed, a case by case determination must be made as to anticipation. In order to anticipate the claims, the claimed subject matter must be disclosed in the reference with "sufficient specificity to constitute an anticipation under the statute." What constitutes a "sufficient specificity" is fact dependent. If the claims are directed to a narrow range, and the reference teaches a broader range, other facts of the case, must be considered when determining whether the narrow range is disclosed with "sufficient specificity" to constitute an anticipation of the claims. Compare ClearValue Inc. v. Pearl River Polymers Inc., 668 F.3d 1340, 101 USPQ2d 1773 (Fed. Cir. 2012) with Atofina v. Great Lakes Chem. Corp, 441 F.3d 991, 999, 78 USPQ2d 1417, 1423 (Fed. Cir. 2006).
In ClearValue, the claim at issue was directed to a process of clarifying water with alkalinity below 50 ppm, whereas the prior art taught that the same process works for systems with alkalinity of 150 ppm or less. In holding the claim anticipated, the court observed that "there is no allegation of criticality or any evidence demonstrating any difference across the range." Id. at 1345, 101 USPQ2d at 1777.
Here, although the lowest group of instant claims is 4 months, the specification does not provide direction regarding the critical age or demonstrating any difference across the age range. One of skill in the art understands that brain size will increase along with additional physiological changes as the child ages, but Hinderer addresses this with increases in dosage levels. Additionally, the age groups are discussed with sufficient specificity, and both prior art and instant claims use the same product (rAAV-IDUA with CB7 promoters and AAV9 capsid protein). Thus the claims directed to age groups are obvious.
Regarding instant claim 1, 55, Hinderer discloses the accumulation of partially degraded glycosaminoglycan (GAG) due to deficiency in IDUA enzyme since IDUA removes terminal iduronic acid from two GAGs called heparan sulfate and dermatan sulfate (pg. 1, lines 17-23). Hinderer’s claim 27 discloses measuring GAG levels in sample of patient’s serum, urine and/or cerebrospinal fluid (CSF). Hinderer demonstrates that “[a]ll animals exhibited a marked reduction in CSF pGAG [i.e. pathologic GAG] concentration 3 weeks after intrathecal AAV injection. This reduction was sustained at day 112” (pg. 62, lines 21-26). Thus, the result of administration of rAAV-hIDUA in a human subject will inherently result in decrease of GAG levels as compared to prior to administration of rAAV-hIDUA.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Hinderer et al. (WO2017136500A1, pub. 08/10/2017, in IDS, referred as Hinderer) and as evidenced by Salvetti et al. (1995, Human Gene Ther., 6, 1153-1159, referred as Salvetti) for claim 1, and in view of Mahan (2014, International J. of Clinical Med., 5, pg. 1374-1383) and Kaplitt et al. (2007, Lancet, 369, 2097-2105) as applied to claims 1, 3, 16, 18, 33, 40, 43, 44, 46, 48, 50, 51, and 52, above.
Claim 17 recites the method of claim 16, wherein the immune suppression therapy is withdrawn after 180 days after a first administration of the rAAV.
Rejection of claims 1, 3, 16, 18, 33, 40, 43, 44, 46, 48, 50, 51, and 52 is disclosed above. Hinderer discloses that immunosuppressive therapy be about 60 days or longer, as needed (pg. 32, line 27); and discloses the immunosuppressive therapy including sirolimus was treated until week 48 visit, which is greater than 180 days) (pg. 53, line 5-7). Thus, Hinderer suggests that the immunosuppressive therapy can be withdrawn at some time after 60 days, including an example of 180 days.
Hinderer, Mahan, Salvetti, nor Kaplitt teach withdrawing immunosuppressive therapy after 180 days.
Thus, although the art does not teach 180 days of immunosuppressive therapy, the 180 days are obvious over Hinderer. The additional duration of 120 days is a necessary optimization to identify the optimal duration of immunosuppressant therapeutic treatment. The necessity would be to suppress negative immune reactions. As noted by Hinderer an MPS I patient would be assessed for neutralizing antibodies (Nab) to AAV antigen interfering with transduction efficiency and reduce therapeutic efficacy, and the therapy would be necessary to prevent potential adverse immune reaction by the patient to the IDUA expressed product. Additionally, instant specification, notes that “[i]mmune suppression therapy can be continued subsequent to the gene therapy, based on the judgement of the treating physician” (par. 213). Thus, further providing that the immunosuppressive therapy duration is based on the need of the patient.
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the immunosuppressant therapy duration of Hinderer and arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to modify the immunosuppressant therapy duration based on the need of the patient as taught by Hinderer to provide for a reasonable expectation of success in identifying optimal duration for immunosuppressant therapy. Thus, cl. 17 is obvious.
Response to Arguments
Applicant's arguments filed 07/06/2026 (“the Remarks”) have been fully considered but they are not persuasive.
The Remarks argue that other ways to show unexpected results include “where the claimed range results in a different property dissimilar to the known property of the prior art” (pg. 7). Here, the Remarks note the unexpected and superior results of the claimed method, including “1) improving patients’ neurodevelopment skills, cognitive function. . . . (2) low levels of total urine GAGs” (pg. 7). The Remarks argue that cited references do not disclose or suggests these parameters or unexpected and superior results.
The argument is not persuasive.
First, the amended claims are rejected as noted above. Second, the kind of cognitive improvements are based on the result of administration of rAAV-hIDUA and Hinderer discloses the improvement in cognitive function in humans following administration of rAAV-hIDUA and demonstrates the reduction of GAG and the parameters are obvious as testing a range of dose is obvious.
Thus, as currently presented, the data of Wang does not appear unexpected.
Thus, the claims remain rejected.
Double Patenting
The rejection of claims 1, 3, 16-18, 33 and 40-52 is maintained, and new claims 53-54 are rejected as noted below.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Application No. 18/480,172 (has been issued a notice of allowance).
Claims 1, 3, 16, 17, 18, 33, 40, 43-44, 46, 48, 50-55 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 36-55 of copending Application No. 18/480,172 (reference application, referred as ‘172). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 1, 3, 18, 50, 51, claim 56 of ‘172 teaches a method of treating MPS I in a pediatric human subject by administering therapeutically effective dose of a recombinant AAV vector carrying an expression cassette encoding a rIDUA via intracisternal or intracerebroventricular injection or lumbar puncture, wherein a glycosylated recombinant human IDUA is produced by human neuronal or glial cells following vector expression, teaches immunosuppressive therapy starting before or concurrently with a first administration of AAV vector; thus at least a single administration (corresponding to instant cl. 1, 3, 50). The inherent result of administration of rAAV of hIDUA to a pediatric human subject would be decrease in neurocognitive decline in human subject and/or claimed reduction of GAG level in biological sample (corresponding to instant cl. 1). Claim 64 teaches SEQ ID NO: 1, which is 100% identical with instant SEQ ID NO: 1, thus would inherently express the same molecular weight as instant cl. 1 (corresponding to instant cl. 1, 18). Claim 62 teaches AAV9 capsid protein. Cl. 65 teaches immunosuppressive therapy is continually administered thereafter (corresponding to instant cl. 3). Further to define therapeutically effective dose, guidance from specification provides a dose of 1×1010 GC/g brain mass (par. 207, corresponding to instant cl. 1, 51).
Regarding claim 16, and 54, claim 66 of ‘172 teaches immune suppression therapy is a combination of tacrolimus, rapamycin and a corticosteroid.
Regarding claim 17, claim 68 of ‘172 teaches immune suppression therapy is withdrawn after 180 days.
Regarding claims 18, 40, 43, claims 1, 62, 63, 64 of ‘172 teaches SEQ ID NO: 1, which is 100% identical with instant SEQ ID NO: 1; expression vector with CB7 promoter, expression vector is rAAV vector, rAAV comprises an AAV9 capsid protein, rAAV comprises an AAVrh10 capsid protein.
Regarding claims 33, 44, 46, 48, and 53, claim 60 of ‘172 teaches human subject is 4 m of age or older, while claim 61 teaches human subject is 3 yr. of age or younger; and claim 1 teaches pediatric human subject. The age range of instant cl. 46 (9m-18m) and 48 (18m-3y) would be obvious, since the instant age range lie within age range of 4m-3y of noted claims of ‘172. Further, since the age range of instant cl. 53 touches the oldest age range, it is also obvious.
Regarding claim 52, claim 1 of ‘172 teaches administering an effective dose and to define therapeutically effective dose, guidance from specification provides a dose of the specification discloses a high dose as 5.6X1010 GC/g brain mass (par. 161). The ‘172 dose approaches instant dose of 5 × 1010 GC/g brain mass, thus is obvious.
Regarding instant cl. 55, as evidenced by Wang post-filing 2023 IND, of record, provides that the majority human patients maintained low levels of total urine GAGs following administration of 1.0X1010 and 5.0X1010 GC/g brain mass rAAV-hIDUA (see slide 12, Remarks of 02/13/2026, pg. 9).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 07/06/2026 (“the Remarks”) have been fully considered but they are not persuasive. The Remarks indicate that the rejection under ‘172 be held in abeyance. The argument is not persuasive and the rejection is maintained.
Alignment of instant SEQ ID NO: 1 (Qy) and Hinderer SEQ ID NO: 2 (Db).
ALIGNMENT:
Query Match 100.0%; Score 3495; Length 653;
Best Local Similarity 100.0%;
Matches 653; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MRPLRPRAALLALLASLLAAPPVAPAEAPHLVHVDAARALWPLRRFWRSTGFCPPLPHSQ 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MRPLRPRAALLALLASLLAAPPVAPAEAPHLVHVDAARALWPLRRFWRSTGFCPPLPHSQ 60
Qy 61 ADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTRGSTGRGLSYNFTHLDGYLDL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADQYVLSWDQQLNLAYVGAVPHRGIKQVRTHWLLELVTTRGSTGRGLSYNFTHLDGYLDL 120
Qy 121 LRENQLLPGFELMGSASGHFTDFEDKQQVFEWKDLVSSLARRYIGRYGLAHVSKWNFETW 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LRENQLLPGFELMGSASGHFTDFEDKQQVFEWKDLVSSLARRYIGRYGLAHVSKWNFETW 180
Qy 181 NEPDHHDFDNVSMTMQGFLNYYDACSEGLRAASPALRLGGPGDSFHTPPRSPLSWGLLRH 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 NEPDHHDFDNVSMTMQGFLNYYDACSEGLRAASPALRLGGPGDSFHTPPRSPLSWGLLRH 240
Qy 241 CHDGTNFFTGEAGVRLDYISLHRKGARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CHDGTNFFTGEAGVRLDYISLHRKGARSSISILEQEKVVAQQIRQLFPKFADTPIYNDEA 300
Qy 301 DPLVGWSLPQPWRADVTYAAMVVKVIAQHQNLLLANTTSAFPYALLSNDNAFLSYHPHPF 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DPLVGWSLPQPWRADVTYAAMVVKVIAQHQNLLLANTTSAFPYALLSNDNAFLSYHPHPF 360
Qy 361 AQRTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQLWAEVSQAGTVLDSNHTVGV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 AQRTLTARFQVNNTRPPHVQLLRKPVLTAMGLLALLDEEQLWAEVSQAGTVLDSNHTVGV 420
Qy 421 LASAHRPQGPADAWRAAVLIYASDDTRAHPNRSVAVTLRLRGVPPGPGLVYVTRYLDNGL 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 LASAHRPQGPADAWRAAVLIYASDDTRAHPNRSVAVTLRLRGVPPGPGLVYVTRYLDNGL 480
Qy 481 CSPDGEWRRLGRPVFPTAEQFRRMRAAEDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHV 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CSPDGEWRRLGRPVFPTAEQFRRMRAAEDPVAAAPRPLPAGGRLTLRPALRLPSLLLVHV 540
Qy 541 CARPEKPPGQVTRLRALPLTQGQLVLVWSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 CARPEKPPGQVTRLRALPLTQGQLVLVWSDEHVGSKCLWTYEIQFSQDGKAYTPVSRKPS 600
Qy 601 TFNLFVFSPDTGAVSGSYRVRALDYWARPGPFSDPVPYLEVPVPRGPPSPGNP 653
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 TFNLFVFSPDTGAVSGSYRVRALDYWARPGPFSDPVPYLEVPVPRGPPSPGNP 653
Conclusion
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/KEYUR A VYAS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600
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