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 11/06/2025 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 05/06/2025 are hereby withdrawn.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 11/06/2025, claims 1, 2, 4-8, 11-13, 16-18, 20 and 28 are pending. Claim 28 is newly added and will be examined as it is in the scope of the elected invention. Claims 4-8, 13, 16-18, 20 and 28 are under examination.
Claims 1, 2, 11 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
The Specification has been accepted correcting the incorporation by reference statement.
The 112(b) rejection has been withdrawn in response to claim amendments and canceled claims.
The 103 rejection is withdrawn in response to claim amendments and a new rejection to address claim amendments is below.
New Claim Rejections - necessitated by claim amendments
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 4-8, 13, 16, 17, 18, 20 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Friedland et al. (US 11,028,411), Rebar (EP3196301 of record cited on P237.IN. filed 06/15/2020) and Haeussler et al. ("Genome editing with CRISPR-Cas9: can it get any better?." Journal of genetics and genomics 43.5 (2016): 239-250 of record cited on 892 mailed 05/06/2025).
Regarding claims 4-6 and 20, Friedland et al. teach a composition in a AAV backbone comprising a two vector system comprising a SaCas9 enzyme in the first AAV and a second vector comprising a gRNA comprising a targeting sequence for a genomic target and teach the second vector can comprise a donor sequence flanked by homology arms wherein this sequence can be in the same vector with a gRNA (col. 43 ln 15-31 and col. 44 ln 15-30).
Regarding claim 18, Friedland et al. teach the vector can be delivered using liposomes (see Table 7).
Friedland et al. do not teach targeting intron 1 of an albumin gene or lysosomal storage disease (LSD).
Regarding the claim 13 and the claim 20 limitation of targeting intron 1 of an albumin gene, Rebar teach LSDs are a group of rare metabolic monogenic diseases characterized by the lack of individual lysosomal proteins normally involved in the breakdown of waste lipids that cause common disease such as iduronidase IDUA, Gaucher’s or Fabry’s (0007). Rebar teach there is a need to develop compositions for treating LSD given other treatments, such as enzyme replacement therapy, only treat the symptoms and are not curative (0007).
Rebar teach compositions for introducing a transgene into a safe harbor gene, such as albumin, of LSD such as an iduronidase and a nucleic acid encoding a sequence for LSD (0010 and 0082). Rebar et al. teach targeting intron 1 in the albumin gene (see Fig. 2, Example 3). Rebar et al. teach the transgene may be introduced using an AAV such as AAV1-9 or AArh10 (0010 and 133). Rebar further discloses wherein the targeting sequence or homology arms are targeted to an intron (paragraphs [0032], [0155]).
Regarding claim 7, Rebar et al. teach the rAAV vectors can be AAV1-9 or AArh10 (0156).
Regarding claim 16, because Rebar et al. teach efficiently targeting the albumin gene, one of skill in the art would have been capable of finding the optimal location within 500 nucleotides of the intron. It is not inventive to discover the optimum or workable ranges by routine experimentation (see MPEP 2144.05 below).
MPEP 2144.05. A. Optimization Within Prior Art Conditions or Through Routine Experimentation.
Generally, 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
It would have therefore been obvious to one of ordinary skill in the art to use the Crispr dual AAV vector of Friedland et al. to target an intron 1 albumin locus taught by Rebar to find an efficient composition for lysosomal storage diseases. Given Rebar teach current treatments only treat symptoms and are not curative, one of skill in the art would have wanted to use the efficient dual AAV vector of Friedland to make a Crispr system to find a cure for lysosomal storage diseases.
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.
In this instance, there is a design need to solve the problem of suitable compositions to treat LSD and a person of ordinary skill has good reason to pursue the known options using the guidance of Rebar who teach finite predictable methods of designing a composition comprising a dual AAV genome editing system such as taught by Friedland et al.
Regarding claims 17 and 28, Haeussler teach et al. SpCas9 variants have been engineered to have a different PAM or higher specificity which greatly improve the flexibility and precision of genome editing the CRISPR-Cas systems (see page 240 first full para). Haeussler teach et al. that while other Cas9 proteins generally have high specificity, there are limits to the range of potential target sequences compared to SpCas9 and SpCas9 is likely to remain the workhorse of genome editing because it can be engineered with novel PAM specificities (see page 247).
It would therefore be obvious to substituted the SaCas9 with SpCas9 given both are used in the Crispr system for gene editing. Furthermore, KSR states that 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. See Board Decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d). Also, see M.P.E.P. §2144.07 which 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.
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.
Claims 4-8, 13, 16, 17, 18, 20 and 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wilson et al. (US 20180110877) and Rebar (EP3196301 of record cited on P237.IN. filed 06/15/2020).
Regarding claims 4-6, 17,18, 20 and 28, Wilson et al. teach a Crispr dual AAV vector system wherein an AAV vector comprises a Cas9 under control of a promoter and a second vector comprises a sgRNA and a donor template (0032, 0041, 0082). Wilson et al. teach the Cas9 can be a SaCas9 or a SgCas9 (0034). Wilson et al. teach diseases such as lysosomal storage disease may be treated with the dual AAV vector system (0055, 0057). Wilson et al. teach the vectors can be delivered using liposomes (0064).
Regarding claims 7 and 8, Wilson et al. teach the AAV can be one of AAV1-9 and while the example shows each vector has the same AAV capsid, other suitable AAV capsids may be used. Therefore it is obvious to use different serotypes for each vector (0049).
Wilson et al. do not teach targeting the intron in the human albumin gene.
Regarding the claim 13 and the claim 20 limitation of targeting intron 1 of an albumin gene, Rebar teach LSDs are a group of rare metabolic monogenic diseases characterized by the lack of individual lysosomal proteins normally involved in the breakdown of waste lipids that cause common disease such as iduronidase IDUA, Gaucher’s or Fabry’s (0007). Rebar teach there is a need to develop compositions for treating LSD given other treatments, such as enzyme replacement therapy, only treat the symptoms and are not curative (0007).
Rebar teach compositions for introducing a transgene into a safe harbor gene, such as albumin, of LSD such as an iduronidase and a nucleic acid encoding a sequence for LSD (0010 and 0082). Rebar et al. teach targeting the intron in the albumin gene of a LSD (see Fig. 2, Example 3 and 0138). Rebar et al. teach the transgene may be introduced using an AAV such as AAV1-9 or AArh10 (0010 and 133). Rebar further discloses wherein the targeting sequence or homology arms are targeted to an intron (paragraphs [0032], [0155]).
Regarding claim 16, because Rebar et al. teach efficiently targeting the intron in the albumin gene, one of skill in the art would have been capable of finding the optimal location within 500 nucleotides of the intron. It is not inventive to discover the optimum or workable ranges by routine experimentation (see MPEP 2144.05 below).
MPEP 2144.05. A. Optimization Within Prior Art Conditions or Through Routine Experimentation.
Generally, 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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
It would have been obvious to target the intron 1 of the albumin gene in making a compound for targeting the LSD as taught by Rebar who teach current methods only treat the symptoms and are not curative.
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.
In this instance, there is a design need to solve the problem of suitable compositions to treat LSD and a person of ordinary skill has good reason to pursue the known options using the guidance of Rebar who teach finite predictable methods of designing a composition comprising a dual AAV genome editing system such as CRISPR-Cas9.
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 Arguments and Amendments
A response to Applicant’s arguments regarding the previous prior art references is unnecessary because known of the previous references were used in the new rejection above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the "right to exclude" granted by a patent and to prevent possible harassment by multiple assignees. See 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);and, 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claims 4-8, 13, 16-18, 20 and 28 as rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-8, 11, 14-16, 18, 20-24, 26 and 35 of U.S. Application No. 17,767,540. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter.
Applicant argues that because this rejection is the only remaining argument left in the O.A. and because U.S. Application No. 17,767,540 is a later filed application, this rejection should be withdrawn. As discussed above, the claims remain rejected and therefore the Double Patent rejection is maintained.
No claims are allowed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a).
706.07(a) Final Rejection, When Proper on Second Action [R-07.2015]
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Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b).
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 extension fee 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 date of this final action.
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 9-5 pm.
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