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 March 31, 2026.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/31/2026 has been entered.
Claim Amendments
Applicant’s amendments to the claims filed 03/31/2026 are acknowledged.
Claims 2, 14, 17, and 19-21 have been cancelled.
Claims 1, 4-5, and 15 are amended.
Claims 1, 3-13, 15-16, 18, and 22 are pending.
Claims 7-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention/species.
Claims 1, 3-6, 13, 15-16, 18, and 22 are under examination.
Election/Restrictions
The following is a summary of the restriction/election requirements in the present application. See the restriction requirement set forth in the Office communications mailed 01/10/2025 and 05/29/2025, and see applicant’s response in papers filed 03/10/2025 and 07/22/2025.
Applicant elected with traverse:
Group 1, drawn to a method of treating a viral infection by administering a genetic modifying agent that targets one or more regions of the virus genome that are maximally different from the subject's genome;
a polymer nanoparticle, as the carrier for the gene modifying agent;
Cas9, as the nuclease; and
HSV-1, as the virus.
As previously stated in the Office action mailed 09/04/2025, the nonelected virus, HSV-2, and the nonelected carriers, adeno-associated virus vector and lentiviral vector, have been rejoined.
As previously stated in the Office action mailed 12/31/2025, the nonelected invention of Group 2, drawn to a method of treating a viral infection by administering a genetic modifying agent that targets one or more genes of host cells which are necessary to the correct function and replication of the virus but dispensable to the host cells, has been rejoined. In this case, the line of demarcation between the elected invention of Group 1 and the nonelected invention Group 2, identified by the examiner in the requirement for restriction, has not been maintained. In particular, in papers filed 12/04/2025, applicant amended claim 1 (Group 1) to recite administration of a genetic modifying agent that “targets one or more regions of the virus genome that are necessary for function or replication of the virus,” which was identified as the technical feature of Group 2 (claim 6).
Claims 7-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention/species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the replies filed on 03/10/2025 and 07/22/2025.
Priority
The instant application 17/640,711 was filed on 03/04/2022. This application is a national stage of international application PCT/US2020/049424 filed 09/04/2020, claiming priority based on U.S. Provisional Patent Application No. 62/897,311 filed 09/07/2019.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 12/31/2025 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.
Claim Interpretation
Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See, MPEP 2173.05(i).
In papers filed 03/31/2026, applicant amended claim 1 to recite the negative limitation: “wherein each [targeted] region is not a multiple repeat region.” Written support under 35 U.S.C. 112(a) relies on paragraph 34 of the specification, disclosing: “Some aspects comprise performing a genome sequence search to identify regions in the viral genome that are maximally different from the host genome. Some aspects comprise using targeting (e.g. with sgRNA) viral genes that are unlikely to target the host genome. Such an approach yields improved efficacy as compared targeting the multiple repeat regions of the viral genome, e.g., as mentioned in Wang, RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection," Proc. Natl. Acad. Sci. USA, 111(36): 13157-62 (2014).”
A paper copy and PTO-892 citation of the disclosed non-patent literature (Wang, 2014, “RNA-guided endonuclease provides a therapeutic strategy to cure latent herpesviridae infection” Proceedings of the National Academy of Sciences, 111(36), 13157-13162) is provided with this Office action. Said disclosure shares authorship and some subject matter with US 2016/0346361 A1 to Quake et al., of record.
Claim Rejections - 35 USC § 102
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 6 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2016/0346361 A1 to Quake et al.
This rejection is repeated for the same reasons provided in the previous Office action. A response to Applicant’s traversal follows this rejection.
Quake discloses guided nuclease systems targeting specific regions of the HSV-1 or HSV-2 genome, disrupting the virus’ nucleic acid and rendering latent viruses incapacitated. The specific regions of the HSV genome include oriS, UL9, RL2 and LAT. The invention is capable of removing latent HSV genetic material from a host organism without interfering with the integrity of the host’s genetic material, and the nuclease is capable of specifically removing only the HSV nucleic acid without acting on host material. A sequence-specific moiety includes a guide RNA (gRNA), and the gRNA localizes a CRISPR/Cas9 nuclease to a HSV target sequence, such as oriS, UL9, RL2 or LAT, thereby selectively editing or destroying the viral genomic material. See, e.g., Abstract; par. 6.
As such, Quake further discloses the treatment of a HSV infection in a subject in need thereof by administration of a composition comprising the guided nuclease systems. See, e.g., par. 9, 14, 19.
Accordingly, regarding claim 6, Quake is found to teach a method of treating a viral infection, the method comprising administering, to a subject infected with a virus, a genetic modifying agent that targets one or more genes of host cells that harbor the virus, where the targeted one or more genes are necessary for a correct and replication of the virus but are dispensable to the host cells.
For these reasons, claim 6 is anticipated by the Quake disclosure.
Response to arguments: Applicant’s remarks filed 03/31/2026 have been carefully considered, but are not found persuasive for the following reasons:
Applicant argues that claim 6 recites that the genetic modifying agent “targets one or more genes of host cells,” and, therefore, claim 6 describes modifying the host cells that harbor the virus, not the viral genome. In contrast, Quake describes targeting the viral genome, not the host genome. See, page 6 of the reply.
The argument is not persuasive. In this case, claim 6 recites that the genetic modifying agent “targets one or more genes of host cells that harbor the virus.” Accordingly, the host cells comprise both (1) non-viral genes, which are native to the cell genome, and (2) viral genes, which are native to the viral genome. Claim 6 does not limit the targeted “one or more genes” to non-viral genes or genes endogenous to the host cell, as argued by applicant. Therefore, claim 6, as presented, includes targeting viral genes, as instantly claimed in claim 1.
Claim Rejections - 35 USC § 103
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.
Claims 1, 3-5, 13, 15-16, 18, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0346361 A1 to Quake et al.; in view of Vakulskas et al. (6 Aug 2019) “Evaluation and reduction of CRISPR off-target cleavage events” Nucleic Acid Therapeutics, Vol. 29, No. 4, pp. 167-174.
This rejection is newly applied, as necessitated by applicant’s amendments. A response to Applicant’s traversal follows this rejection.
Quake discloses guided nuclease systems targeting specific regions of the HSV-1 or HSV-2 genome, disrupting the virus’ nucleic acid and rendering latent viruses incapacitated. The specific regions of the HSV genome include OriS, UL9, RL2 and LAT. The invention is capable of removing latent HSV genetic material from a host organism without interfering with the integrity of the host’s genetic material, and the nuclease is capable of specifically removing only the HSV nucleic acid without acting on host material. A sequence-specific moiety includes a guide RNA (gRNA), and the gRNA localizes a CRISPR/Cas9 nuclease to a HSV target sequence, such as OriS, UL9, RL2 or LAT, thereby selectively editing or destroying the viral genomic material. See, e.g., Abstract; par. 6.
As such, Quake further discloses the treatment of a HSV infection in a subject in need thereof by administration of a composition comprising the guided nuclease systems. See, e.g., par. 9, 14, 19.
Accordingly, regarding claim 1, Quake is found to teach a method of treating a viral infection, the method comprising administering, to a subject infected with a virus, an effective amount of a genetic modifying agent that targets one or more regions of the virus genome that are necessary for function or replication of the virus, and wherein upon administration, the genetic modifying agent edits the virus genome in said one or more regions, thereby treating the viral infection.
Claim 1 further recites that each targeted region as less than 20% sequence identity with any region of the subject’s genome. Quake discloses that the gRNA targeting sequence has no match >60% within a human genome (see, e.g., par. 12, 17), which is equivalent to a range of 60% or less sequence identity with any region of the subject’s genome.
"[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).
Where the claimed ranges "overlap or lie inside ranges disclosed by the prior art," a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997); In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941). See, MPEP 2144.05.
In this case, Quake discloses a method of treating a viral infection using a gRNA targeting sequence having 60% or less sequence identity with any region of the subject’s genome, which overlaps with the instantly claimed range of less than 20% sequence identity. Quake further discloses the gRNA is designed to satisfy a similarity criteria that matches the target viral genome sequence without any off-target matching with the host genome, such that the latent viral genetic material is removed from the host without any interference with the host genome. See, e.g., par. 162. Accordingly, Quake fairly suggests that minimizing homology between the targeted viral region and any rejoin in the subject’s genome is desirable to reduce off-targeting effects. Moreover, means of reducing homology and minimizing off-target events of CRISPR/Cas9 systems were known in the art prior to the effective filing date of the instantly claimed invention. See, e.g., Vakulskas on pages 167-170. Therefore, one of ordinary skill in the art would have recognized that the sequence homology between the gRNA targeting sequence and any region of the subject’s genome is a result-effective variable that may be optimized through routine experimentation, and one of ordinary skill in the art would have been led to improve upon the prior art (Quake) by reducing said sequence homology, as instantly claimed, in order to reduce off-targeting effects.
Accordingly, absent evidence of criticality, the claimed range of less than 20% sequence identity with any region of the subject’s genome, as recited by claim 1, would have been prima facie obvious over the prior art.
Claim 1 further recites the negative limitation: “wherein each [targeted] region is not a multiple repeat region.”
Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See, MPEP 2173.05(i).
"[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). See, MPEP 2144.01.
In this case, Quake does not disclose targeting the multiple repeat regions of the HSV genome. Rather, Quake teaches targeting other regions of the HSV genome, such as OriS, UL9, RL2 or LAT, so as to remove only the HSV nucleic acid without acting on the host material (par. 6). Such an approach was adopted in the working examples targeting HSV (Example 1, par. 172-175). Accordingly, Quake specifically teaches designing gRNAs targeting the OriS, UL9, RL2 or LAT regions of the HSV genome, as opposed to targeting the multiple repeat regions of the HSV genome. Moreover, in the working examples targeting EBV (Example 2, par. 176-221), Quake describes designing gRNAs targeting with multiple repeat regions as well as gRNAs target other regions of the EBV genome. See, in particular, par. 182, 184, 191, and fig. 8. Accordingly, with respect to at least targeting the EBV genome, Quake specifically contemplates gRNAs targeting multiple repeat regions or, in the alternative, gRNAs targeting other regions of the viral genome. Thus, for the reasons outlined above, one of ordinary skill in the art would have found in Quake, or reasonably inferred therefrom, that the gRNAs are not designed to target a multiple repeat region, as instantly claimed.
Claim 1 further recites that the claimed therapeutic exhibits improved efficacy by targeting one or more regions of virus genome relative to targeting the host genome.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003). See, MPEP 2112.
In this case, the limitation wherein improved efficacy is achieved by targeting regions of the viral genome rather than the host genome describes an intended result or functional property of performing the process steps (manipulative actions) positively recited in claim 1. A recitation of an intended result or functional property of the claimed process must result in a manipulative difference between the claimed process and the cited prior art in order to patentably distinguish the claimed process from the cited prior art. If the prior art process is capable of performing the intended result, or if the functional property naturally flows from the prior art process, then the prior art reads on the intended result or functional property recitation. There is no requirement that the cited prior art expressly teach or suggest the intended result or functional property recitation, but only that the subject matter is, in fact, present in the cited prior art. As outlined above, the manipulative actions positively recited by the claims would have been prima facie obvious over the cited prior art. In particular, Quake describes targeting one or more regions of the viral genome rather than the host genome, as claimed in claim 1. Therefore, the intended result or functional property of wherein improved efficacy is achieved by targeting one or more regions of the viral genome rather than the host genome would have naturally flowed from performing the process steps taught by Quake. Moreover, Quake expressly teaches that the administration of guided nuclease systems targeting specific regions of the HSV genome, thereby disrupting the virus’ nucleic acid and rendering latent viruses incapacitated, is therapeutically effective (efficacious) in the treatment of an HSV infection. See, e.g., Abstract, and par. 9, 14, 19.Accordingly, absent evidence to the contrary, the intended result or functional property recitations, as instantly claimed, are not found to patentably distinguish the claimed invention from the cited prior art.
For these reasons, claim 1 would have been prima facie obvious over the prior art.
Regarding dependent claim 3, Quake discloses that selection of the delivery vector (carrier) is based upon “the cell or tissue targeted” (par. 137); the surface of cationic non-virals can be modified to “increase their binding affinity with the target cells” (par. 118); targeting ligands can be attached to PEGylated nanoparticles to “allow binding to receptors on the target cell surface” (par. 120). For these reasons, Quake fairly suggests that the guided nuclease systems are delivered via carriers modified to possess increased affinity for targeted cell types or tissue types harboring the viral infection, as claimed.
Regarding dependent claim 4, Quake discloses the guided nuclease systems are delivered by a vector or carrier, such as a retrovirus, lentivirus, adeno-associated virus, nanoparticle, cationic polymer, liposome or liposphere. See, e.g., par. 13, 18.
Regarding dependent claim 5, Quake discloses that the nanoparticles comprises cholesterol, a lipid-PEG compound and/or distearoylphosphatidylcholine (par. 119, 123).
Regarding dependent claims 13, 15-16, Quake discloses that the guided nuclease system is a Cas9 protein and guide RNA. See, e.g., par. 6.
Regarding dependent claim 18, Quake discloses the nuclease or gene encoding the nuclease may be modified or programmed to be active under only certain conditions such as by using a tissue-specific promoter so that the encoded nuclease is preferentially or only transcribed in certain tissue types (par. 104). Accordingly, when using a “tissue-specific promoter,” the genetic modifying agent is “activated” or “deactivated” depending upon whether or not the necessary biological input is provided by the infected tissue type.
Regarding dependent 22, Quake discloses the virus is HSV-1 or HSV-2. See, e.g., Abstract.
Response to arguments: Applicant’s remarks filed 03/31/2026 have been carefully considered, but are not found persuasive for the following reasons:
Applicant argues that Quake teaches that the targeted regions have 60% or less sequence homology with any region of the host genome, but the threshold 60% match is likely too dissimilar to allow targeted nuclease activity, and such a lenient threshold would permit off-target matches and/or unwanted host genome nuclease activity. See, page 7 of the reply.
Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). See, MPEP 716.01(c).
In this case, Applicant has not provided objective evidence that a 60% match is too dissimilar to allow targeted nuclease activity and would permit off-target matches and/or unwanted host genome nuclease activity. Moreover, the argument is contradicted by the Quake disclosure disclosing that the invention is capable of removing latent HSV genetic material from a host organism without interfering with the integrity of the host’s genetic material, and the nuclease is capable of specifically removing only the HSV nucleic acid without acting on host material. The invention was further reduced to practice in the working examples (starting in par. 172).
The remainder of applicant’s remarks have been carefully considered, but are found to be addressed and/or obviated by the new grounds of rejection set forth in this action.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631
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