Polymer-Encapsulated Viral Vectors for Genetic Therapy

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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8/27/ has been entered. Applicant has amended the claims to specific that the nanoparticle is a retroviral vector. The rejections are maintained for the reasons of record because the art utilized for the rejection uses a lentivrus vector which is a retrovirus. Applicant argues “contrary to the rejection's mischaracterization of White, it was accepted at the time of the invention that retroviruses require a viral fusion protein in order to enter cells. Further, the entry mechanism requires a co -receptor in the target cell, leading to "tropism" of the virus that can limit vector targeting and can lead to undesired side-effects. The present invention overcomes such tropism related to viral fusion proteins by removing them from the vector.” Applicant's arguments have been considered however a showing to overcome a prima facie case of obviousness must be clear and convincing( In re Lohr et al. 137 USPQ 548) as well as commensurate in scope with the claimed subject matter ( In re Lindner 173 USPQ 356; In re Hyson, 172 USPQ 399 and In re Boesch et al., 205 USPQ 215 (CCPA 1980). Given the breadth of this argument, one would have to think that the ability of the claimed invention to work would be limited to the specific example or a clear explanation of and how (if at all) this data could be extrapolated to the elected invention or even the generic. 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. Claims 1, 3-5, 7, 10-11 and 13-16, and 47-48 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/093966 (966) and White et al (attached 892). . The generic claims are rendered obvious. 966 describes nanocapsules comprising a viral vector, e.g. a lentiviral vector, coated with a polymer. The polymer is coupled to one or more targeting agent, such as antibody, peptides, ligands, receptors, ... The nanocapsule has a higher stability. It is use for gene therapy, cancer therapy. The vector is completely coated (Abstract; Pages 3, 4, 9; example 2). 966 does not teach where the viral vector lacks an envelop protein as the vectors of 966 are pseudotyped however it would have been obvious at the time the invention was filed to use a vector wherein that lacks envelop proteins because such modified vectors are old and well known in the art as taught by White which is a review article that discusses the use and safety of non-pseudotyped lentiviruses. It would have been obvious at the time the invention was filed to use and known useful lentivirus vector in the invention of 966 as an obvious design choice depending on the tropism or safety needed/desired in the particular application for the vector. Applicant is directed to pages 12-13 of KSR v Teleflex (500 US 398 2007) “ … the Court has held that a “patent for a combination which only unites old elements with no change in their respective functions . . . obviously withdraws what is already known into the field of its monopoly and diminishes the resources available to skillful men.” Great Atlantic & Pacific Tea Co. v. Supermarket Equipment Corp., 340 U. S. 147, 152 (1950). This is a principal reason for declining to allow patents for what is obvious. The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” “When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one(emphasis added). If a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.” "[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) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time the invention was made especially in the absence of evidence to the contrary. Claims 1, 3-5, 7, 10-11 and 13-16, and 47-48 (as they read on the elected species) are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/093966 (966) and White et al and WO 2014/136100 (100). 966 and White et al are described above. ‘966 does not teach wherein the polymer coating for the nanoparticle is the modified PBAE (as elected) however it would have obvious to use such a PBAE as it is a known polymer for the delivery of transgene vectors as taught by ‘100 (see whole Doc- esp Formulas) and would be obviously substituted into the particle of ‘966 because it is biocompatible and biodegradable (see esp ’699 p4-5; ‘100 p 2). ‘966 and ‘100 additional targeting moieties thus using a known targeting moiety like anti-CD3 would’ve been obvious to one of ordinary skill in the art of gene therapy. Applicant is directed to pages 12-13 of KSR v Teleflex (500 US 398 2007) “ … the Court has held that a “patent for a combination which only unites old elements with no change in their respective functions . . . obviously withdraws what is already known into the field of its monopoly and diminishes the resources available to skillful men.” Great Atlantic & Pacific Tea Co. v. Supermarket Equipment Corp., 340 U. S. 147, 152 (1950). This is a principal reason for declining to allow patents for what is obvious. The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” “When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one(emphasis added). If a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill.” The transgenes used would have been obviously selected from those known and desirable in the art such as the elected generic chimeric antigen receptor. "[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) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). Applicant's arguments have been considered however a showing to overcome a prima facie case of obviousness must be clear and convincing( In re Lohr et al. 137 USPQ 548) as well as commensurate in scope with the claimed subject matter ( In re Lindner 173 USPQ 356; In re Hyson, 172 USPQ 399 and In re Boesch et al., 205 USPQ 215 (CCPA 1980). Applicant alleges the unexpected use of a non-pseudotyped coated vectors to transduce cells and this is potentially but the data in Fig 13-14 would need to be more clearly explained as to what specific experiments produced this unexpected result and how (if at all) this data could be extrapolated to the elected invention or even the generic. Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time the invention was made especially in the absence of evidence to the contrary. Any inquiry concerning this communication or earlier communications from the examiner should be directed to BLAINE LANKFORD whose telephone number is (571)272-0917. The examiner can normally be reached M-Th 8-6:30. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached on 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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