DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 321-341 are pending.
The instant application claims as a continuation of U.S. serial 15/737,723 filed 12/18/2017 now U.S. Patent 11,414,657 which claims priority under 371 of PCT/US16/40191 filed 6/29/2016 which claims priority to U.S. provisional applications 62/186,363 filed 6/29/2015, U.S. provisional 62/233, 281 filed 9/25/2015 and U.S. provisional application 11/17/2015.
The claimed subject matter which was entered with a preliminary amendment on 2/21/2025 comprises new matter as set forth below. As the claimed invention does not have support in the disclosures previously filed, the effective filing date for art purposes of the claims is 2/21/2025.
Information Disclosure Statement
Information disclosure statements filed 11/6/2024 and 9/20/2022 have been identified and the documents considered. The corresponding signed and initialed PTO Form 1449 has been mailed with this action. Initials indicate that the document has been considered even if the reference is lined through. In the case that only an English abstract was identified, this is indicated.
Specification
The disclosure is objected to because of the following informalities: the disclosure appears to contain a misspelling of CRISPR in ¶0394 of the PGPUB of this application.
Appropriate correction is required.
Claim Objections
Claims 321, 326 and 330 are objected to because of the following informalities: in claim 321, crRNA which stands for CrisprRNA should be spelled out on its first occurrence. Similarly, abbreviations are found in claims 326 (2”-OMe and 2’-F) and 330 (LNA and cEt) which are not accompanied by the full spelling.
Appropriate correction is required.
Claim Rejections - 35 USC § 112, first paragraph
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.
Claims 321-341 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that this is a new matter rejection as the subject matter was introduced with an amendment filed 2/21/2025. The MPEP teaches, “New or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement. See, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971) (subgenus range was not supported by generic disclosure and specific example within the subgenus range); In re Smith, 458 F.2d 1389, 1395, 173 USPQ 679, 683 (CCPA 1972) (a subgenus is not necessarily described by a genus encompassing it and a species upon which it reads). (see e.g. MPEP 2105).
The claims are drawn to a crRNA comprising a 5’ region, an internal region and a 3’ region. These designations are not on their own without description as all molecules will comprise a 5’ and a 3’ end with an internal region. However, the claims are drawn to specific properties wherein, the 5’ region comprises 7-10 nucleosides wherein at least one nucleoside comprises a modified sugar base, an internal region with 10 linked nucleosides with no more than one nucleoside comprising a modified sugar moiety and a 3’ region of 12-22 nucleosides wherein at least 4 nucleosides comprise a modified sugar moiety.
The disclosure to the contrary does not teach these designations either explicitly or inherently. The disclosures provides for a linked DNA recognition domain and a tracrRNA recognition domain.
[0394] In certain embodiments, the present invention provides modified oligonucleotides for use in CRISPR. Typically, CRISPR employs CRSPR RNA (crRNA), which hybridizes to target DNA and also hybridizes to trans-activating RNA (tracrRNA), which in turn recruits a nuclease, cas9, which cleaves the target DNA. Thus, the crRNA in such systems has two functions: (1) recognition and hybridization to the target DNA and (2) recognition and hybridization to the tracrRNA. Typically, in such systems, the crRNA has two portions which correspond to these two functions: a DNA recognition portion and a tracrRNA recognition portion. The present invention provides modified oligonucleotides that may be used in crRNA. Such modified oligonucleotides may have modifications in the DNA recognition portion and/or tracrRNA recognition portion.
These are provided as the only two portions. In the disclosure, the DNA recognition portion comprises at least 7 nucleosides (¶0065) and in another no more than 17 nucleotides (see ¶0082). The tracrRNA is provided for as 12 or fewer linked nucleosides (¶0081) and also under 22 nucleotides (see ¶0482).
[0483] Modified crRNAs having the motifs described in the table below can be used for any crRNA nucleobase sequence. The first 17 to 20 nucleosides of each motif represent the DNA recognition portion of the crRNA, and the remaining 12 to 22 nucleosides of each motif represent the tracrRNA recognition portion of the crRNA. The motifs labeled “29-mers” contain 29 linked nucleosides, and the motifs labeled “42-mers” contain 42 linked nucleosides.
In the tables, the provided for sequences are marked by an underlined region and a non-underlined region that correspond to a DNA recognition domain and a tracrRNA. But, the designation of a 5’ region, an internal region and a 3’ region of a molecule seems to provide artificial boundaries where they do not exist in the disclosure. This creates a situation where the end of the 5’ region and the beginning of the internal domain has to be conjectured throughout all the sequences provided to identify those sequences that fit the claims.
To this end, the MPEP provides such guidance. If the application as filed does not disclose the complete structure (or acts of a process) of the claimed invention as a whole, determine whether the specification discloses other relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention. The written description requirement may be satisfied through disclosure of function and minimal structure when there is a well-established correlation between structure and function. In contrast, without such a correlation, the capability to recognize or understand the structure from the mere recitation of function and minimal structure is highly unlikely. In this latter case, disclosure of function alone is little more than a wish for possession; it does not satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Compare Fonar, 107 F.3d at 1549, 41 USPQ2d at 1805 (disclosure of software function adequate in that art).
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 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 340 and 341are 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 a method of transforming a cell in vitro, the method comprising contacting the cell in vitro with the oligonucleotide of claim 335 wherein the oligo comprises a 5'-region, an internal region, and a 3'-region:the 5'-region consists of 7-10 linked nucleosides, wherein at least one nucleoside comprises a modified sugar moiety; the internal region consists of 10 linked nucleosides, wherein no more than one nucleoside comprises a modified sugar moiety; and the 3'-region consists of 12-22 linked nucleosides; wherein at least 4 nucleosides of the 3'-region comprise a modified sugar moiety; and wherein the third nucleoside from the 5'-end of the 3'-region comprises an unmodified RNA sugar moiety and the DNA recognition portion is complementary to the target sequence, is not enabled for any other use.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the patent coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is not based on a single factor but is rather a conclusion reached by weighing many factors (See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter, 1986) and In re Wands, 8USPQ2d 1400 (Fed. Cir. 1988); these factors include the following:
1) Nature of invention. The instant claims are drawn to a method comprising contacting any cell with the crRNA which comprises a 5'-region, an internal region, and a 3'-region:the 5'-region consists of 7-10 linked nucleosides, wherein at least one nucleoside comprises a modified sugar moiety; the internal region consists of 10 linked nucleosides, wherein no more than one nucleoside comprises a modified sugar moiety; and the 3'-region consists of 12-22 linked nucleosides; wherein at least 4 nucleosides of the 3'-region comprise a modified sugar moiety; and wherein the third nucleoside from the 5'-end of the 3'-region comprises an unmodified RNA sugar moiety.
2) Scope of the invention. The scope of the invention is extremely broad in that the method requires only contacting any cell with the oligonucleotide of claim 321 or 338 both of which are generically claimed crRNA sequences. These sequences usually operate with CRISPR but CRISPR is not used as part of the invention. Hence, the purpose, the goal, the target and the sequence are broadly claimed.
3) Number of working examples and guidance. The claims are drawn to an oligonucleotide to be used as a crRNA.
[0394] In certain embodiments, the present invention provides modified oligonucleotides for use in CRISPR. Typically, CRISPR employs CRSPR RNA (crRNA), which hybridizes to target DNA and also hybridizes to trans-activating RNA (tracrRNA), which in turn recruits a nuclease, cas9, which cleaves the target DNA. Thus, the crRNA in such systems has two functions: (1) recognition and hybridization to the target DNA and (2) recognition and hybridization to the tracrRNA. Typically, in such systems, the crRNA has two portions which correspond to these two functions: a DNA recognition portion and a tracrRNA recognition portion. The present invention provides modified oligonucleotides that may be used in crRNA. Such modified oligonucleotides may have modifications in the DNA recognition portion and/or tracrRNA recognition portion.
The tracrRNA recognition portion is provided as direct repeat sequences. The oligo is claimed broadly in terms of whether the sequences comprise specific locations of modified vs unmodified sugar bases. The sequences are not limited just the size and modification states. The disclosure teach that by altering modifications in the improve stability by stabilizing the 5’ and/or 3’ end. As well, there is increase affinity for target DNA.
In the examples, modified crRNAs comprising a DNA recognition portion complementary to hLDLR and demonstrated improved activity when the linkage was phosphorothioate and 2’-O-methyl modified (Example 1 and Table 1). As well, the results demonstrate that modification of the sugar moieties of a crRNA designed to cleave VEGFa increases cleavage as compared to sgRNA with no particular pattern (Example 2, Table 2). Further modifications to incorporate seven 2’-F modifications at the 5’ end and insert five cET modifications into the 3’ end lead to increased cleavage of VEGFa (table 3, example 3). Example 3 shown in Table 4 shows results not pertinent to the claims as they are drawn to shortened oligos. In example 5, modified crRNAs have 17-20 nucleosides are the DNA recognition portion and the remaining 12-22 represent the tracrRNA recognition portion.
4) State of the art. The instant invention is directed to use of crRNA (gRNA) which is part of the CRISPR/Cas system. However, the claim does not provide for introduction or use of CRISPR with the crRNA. Further, the steps do not limit the method to in vitro. At the time of filing, the art was clear that delivery of and activity of Cas9 and gRNAs in vivo are hindered by delivery issues. Mout et al (2017)
The successful use of clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-based gene editing for therapeutics requires efficient in vivo delivery of the CRISPR components. There are, however, major challenges on the delivery front.
Overall, CRISPR/Cas9 ribonucleoprotein delivery seems to be superior to gene delivery as it offers numerous advantages: transient delivery, no insertional mutagenesis, low immunogenicity, and low off-target effect. As highlighted above, very few Cas9-RNP in vivo delivery methods have been reported. Numerous challenges in the delivery front needed to be solved before translating this technology into clinics. These challenges, however, open up exciting opportunities in the CRISPR/Cas9 in vivo delivery front.
Even well past filing the issues have not been resolved, Wilbie et al (2019),
In this Account, we focus on the delivery aspects of CRISPR/Cas for therapeutic applications in vivo. Safe and effective delivery of the CRISPR/Cas components into the nucleus of affected cells is essential for therapeutic gene editing. These components can be delivered in several formats, such as pDNA, viral vectors, or ribonuclear complexes. In the ideal case, the delivery system should address the current limitations of CRISPR gene editing, which are (1) lack of targeting specific tissues or cells, (2) the inability to enter cells, (3) activation of the immune system, and (4) off-target events.
Hence, CRISPR technology suffers from the issue of all gene therapy methods. Gene delivery has been a persistent problem for a variety of reasons including the route of delivery, immunogenicity, packaging, targeted delivery, off target effects and more. Viral vectors are hindered by packing challenges as well as obstacles with delivery routes (reviewed by Mout et al, page 880-882). The major issues with delivery are organ barriers, failure to persist, side-effects in other organs, T-cell responses, virus neutralizing antibodies, humoral immunity, normal tropism of the vector to other organs and more (see Fumoto et al). It is not a question of safety but one of predictability.
This is exacerbated by immunity against CRISPR (Wilbe et al),
Since the CRISPR system is of bacterial origin, an immune reaction against one of its components is likely to occur when it is administered for direct in vivo genome editing.(38) Moreover, the type of delivery vector used may fortify this immune response and should therefore be carefully chosen. The mode of delivery (e.g., as gene construct, mRNA, or RNP) will also influence the overall immunogenicity of the gene editing system as longevity of Cas protein expression generally favors antigen presentation and thus potential activation of adaptive immune responses.(39,40)
By far the biggest hurdle for widespread in vivo application of CRISPR/Cas is the immunogenicity of the CRISPR/Cas components. Although encapsulation of the components in nanocarrier systems might temporarily cause protection against antibody binding and neutralization, eventually the components need to be released to exert their gene editing action. Cellular responses against cells expressing Cas9 have been described, which pose a serious threat to the success and safety of in vivo gene editing. Strategies to mitigate such immune responses, including coadministration of immunosuppressive drugs, should therefore be explored.
5) Amount of Experimentation Required. Applicants examples are limited to in vitro and prophetic examples. The method of introducing furthermore requires CRISPR in the art and the disclosure. Consequently, the prior art (and post-filing art) when combined with the lack of any disclosed direct experimental test of Applicant's hypothesis, shows that one of skill in the art at the time the invention was made would have had no basis to reasonably predict or conclude the claimed method could overcome the art known obstacles for in vivo use. Though not controlling, the lack of working examples, is, nevertheless, a factor to be considered in a case involving both physiological activity and an undeveloped art. When a patent applicant chooses to forego exemplification and bases utility on broad terminology and general allegations, he runs the risk that unless one with ordinary skill in the art would accept the allegations as obviously valid and correct, the PTO may, properly, ask for evidence to substantiate them. Ex parte Sudilovsky, 21 USPQ2d 1702, 1705 (BPAI 1991); In re Novak, 134 USPA 335 (CCPA 1962); In re Fouche, 169 USPQ 429 (CCPA 1971).
And quite simply, there is no evidence in the art and the specification does not advance that this method could be performed in vivo. It is not clear the molecules could make it to “a targeted gene” and as well the broad nature of the cell and the target gene is an unpredictable array of combinations that have so much unpredictability. The “predictability or lack thereof in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. If one skilled in the art can readily anticipate the effect of a change within the subject matter to which the claimed invention pertains, then there is predictability in the art. On the other hand, if one skilled in the art cannot readily anticipate the effect of a change within the subject matter to which that claimed invention pertains, then there is lack of predictability in the art. Accordingly, what is known in the art provides evidence as to the question of predictability M.P.E.P. § 2164.03. Considering the specifics of the arguments, applicants have not established any facts to the contrary of what is established here.
6) Amount of Experimentation Required. The claims have been evaluated in light of the art at the time of filing and found not to be commensurate in scope with the specification. MPEP 2164.05 teaches, “However, the examiner should carefully compare the steps, materials, and conditions used in the experiments of the declaration with those disclosed in the application to make sure that they are commensurate in scope; i.e., that the experiments used the guidance in the specification as filed and what was well known to one of skill in the art. Such a showing also must be commensurate with the scope of the claimed invention, i.e., must bear a reasonable correlation to the scope of the claimed invention. The invention recites use of a broad group of sequence. In the ideal case, the delivery system should address the current limitations of CRISPR gene editing. In this absence and in light of the large breadth, given the unpredictability of the art, the poorly developed state of the art, the lack of adequate working examples and the lack of guidance provided by applicants, the skilled artisan would have to have conducted undue, unpredictable experimentation to practice the claimed invention.”
Claim Rejections - 35 USC § 102
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 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.
Claims 321-325, 327 and 329-341 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bellinger et al (U.S. 20240390520).
Bellinger et al teach an oligonucleotide that meets the limitations of the claims. The instant claims are not size limited but require 3 domains. The first is a 5’ region of 7-10 linked nucleosides wherein at least one comprises a modified sugar moiety, an internal region consisting of 10 linked nucleosides wherein no more than one nucleosides comprises a modified sugar moiety and a 3’ region consisting of 12-22 linked nucleosides wherein at least 4 comprise a modified sugar moiety and the third from the 5’ end of this region is unmodified.
Bellinger teaches a crRNA with a DNA recognition domain and a tracrRNA recognition domain that are a single molecule as recited in claim 338 (see e.g. ¶0143). There are multiple examples wherein
“uppercase nucleotides (A, C, G, I and U) indicate ribonucleotides, adenine, guanine, cytosine, inosine, and uracil, respectively and lowercase nucleotides (a, g, c, i and u) indicate 2′-O-methylribonucleotide (2′-OMe) unless otherwise specified. It is understood that the DNA protospacer is converted to RNA or RNA-equivalent in the guide RNA design except when other modification including 2′-deoxyribonucleotides are introduced into the protospacer section of the single guide RNA; s: phosphorothioate (PS) dA, dC and dG indicate 2′-deoxyadenosine, 2′-deoxycytidine and 2′-deoxyguanosine; dU indicates thymidine and/or 2′-deoxyuridine, and Z indicate zebularine or 4-deoxyuridine/4-deazacytidine. Y or Y indicates pseudouridine, N1mY or N1mY indicates N1m-pseudouridine, MP-U indicates 2′-O-methyl-3′-phosphonoacetate-uridine, dW indicates 2′-deoxyethynylmethylpyridone-cytidine, 2,6-DAP indicates 2,6-diaminopurine, and a ″+″ symbol (+A, +G, +C, +U) indicate locked nucleic acids. X is nebularine.”
The one below meets claim 321 and 333 wherein the 7-10 nucleotides of the 5’ region comprise at least one modified sugar, the 10 internal lack modifications and the 3’ region comprises at least 4 and an unmodified nucleoside at the 5’ end (nucleoside 22).
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As recited in claim 322, the 5’ most nucleoside is modified. And as recited in claim 323, at least 5 of the 5’ region are modified.
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In this sequence, claims 324 and 325 are met (all the first 7 nucleosides are modified). It is noted in each of these that claim 327 is met (internal 10 nucleosides are not modified). As well as recited in claim 329, the 3’ modifications are 2’-OMe. As claim 330 limits the bicyclic choice should it be made it does not require the bicyclic moieties in claim 330.
Backbone modifications selected from phosphodiester and phosphorothioate are included in the teachings (see ¶ 0089) as recited in claim 331- 332.
The 3’ region is tracrRNA (see ¶0144) as recited in claim 336 and 337.
Bellinger teaches “spacer regions contain unique sequence complementary to a DNA target site sequence”. This traditionally means that it is 100% related and hence claim 334 and 335 are met.
As to claims 339 and 340, the crRNA are designed to be used with CRISPR to be introduced into cells (see e.g. ¶0587).
Claims 321-341 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Radhar et al (PNAS, 2015, pages E7110-E7117, provided in IDS).
Radhar et al teach an oligonucleotide that meets the limitations of the claims. The oligo comprises a 5’ region of 7-10 linked nucleosides wherein at least one comprises a modified sugar moiety, an internal region consisting of 10 linked nucleosides wherein no more than one nucleosides comprises a modified sugar moiety and a 3’ region consisting of 12-22 linked nucleosides wherein at least 4 comprise a modified sugar moiety and the third from the 5’ end of this region is unmodified.
Radhar teaches a crRNA as recited in claim 321 with a single molecule as recited in claim with the arrangement of claim 1 wherein a 5’ region between 7 and 10 nucleosides comprises 5 modifications as required in claim 323 and 333, an internal domain with no modifications and a 3’ region comprising only 5 modifications as recited in claim 328 with a 3rd nucleoside that is not modified. (see Figure 1). It is noted that the instant claims do no occlude additional sequences and hence the 11 nucleoside length is the 5’ region and an extra nucleotide. The 5’ most nucleoside is modified as recited in claim 322.
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In figure 3, all of the 5’ sequences are modified and this domain is limited to 10 nucleosides as required of claims 324 and 325). The green and red are 2’OMe and 2’-F.
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The 5’ modifications are al 2’-OMe as recited in claim 326. It is noted in each of these that claim 327 is met (internal 10 nucleosides are not modified). As well as recited in claim 328 and 329, the five 3’ modifications are 2’-OMe. As claim 330 limits the bicyclic choice should it be made it does not require the bicyclic moieties in claim 330.
Backbone modifications are phosphorothioate (see page E7112, col 1) as recited in claim 331- 332.
The 3’ region is tracrRNA as recited in claim 336 and 337. The sequences bind of 100% to a target (see figure 1A. As to claims 339 and 340, the crRNA are designed to be used with CRISPR to be introduced into cells (see Figure 2).
Double Patenting
A rejection based on double patenting of the "same invention" type finds its support in the language of 35 U.S.C. 101 which states that "whoever invents or discovers any new and useful process ... may obtain a patent therefor ..." (Emphasis added). Thus, the term "same invention," in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957); and In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970).
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) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent is shown to be commonly owned with this application. See 37 CFR 1.130(b).
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 321-333 and 336-341 are provisionally rejected under the judicially created doctrine of obviousness-type double patenting as being unpatentable over claims 1-8 and 10-12 of U.S. Patent 11,414,657.
An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim is not patentably distinct from the reference claims because the examined claim is either anticipated by, or would have been obvious over, the reference claims. Although the conflicting claims are not identical, they are not patentably distinct from each other because the cited claims of the instant invention are generic to all that is recited in claims 1-8 and 10-12 of U.S. Patent 11,414,657. That is, the cited claims of U.S. Patent 10,016,458 anticipate and fall entirely within the scope of the rejected claims of the instant application.
Claim 1 of the patent and claim 321 (and claim 333) overlap in the following manner. The patent and the instant claims each comprise a 5’ terminus with an overlap of 7 nucleotides with modifications that include non-bicyclic (instant claim 325 and 326). The copending patent comprises as to the remainder of the crRNA, at least 10 consecutive nucleosides that comprise unmodified sugar moieties at the 3’ end. Considering a crRNA that is 32 nucleosides as required in the patent claims, this allows for 10 unmodified nucleosides from the 3’ end that are unmodified (as required of the patent) and leaves 5 nucleosides in this 3’ region that can comprise the 3rd nucleoside from the 5’ end that is unmodified and 4 that are modified (as required of the instant claims). The instant arrangement of the instant claim 321-325 would be thus wherein the shaded parts are the required components of the instant claims. And as claim 329-330 and instant claim 2, the modification in the “3’end” can be cET.
[AltContent: rect][AltContent: rect][AltContent: rect][AltContent: rect][AltContent: ]7 nucleosides
(all modified)
The internucleoside linkage is phosphorothioate internucleoside as recited in claim 331 and 332.
As to copending claim 3 and as set forth above, the 7 5’ nucleosides can be 2’OMe or 2’-F (see claim 326).
As to copending claim 4-6, base claim 321, 328 requires 5 total between the internal and 3’ end and this is met by copending claims 5-6. Both sets of claims allow for 10 unmodified RNA sugar moieties (instant claim 327, copending claim 1).
The 3’ end if the tracr has a possible configuration that allows for kr3-kr3 as recited in claim 7 if the 1st and 2nd prior to the unmodified required sequence are modified. .
As recited in claims 336-337, the copending claim requires a tracrRNA, this also meets copending claim 8.
The instant claims are generic to all recited in claims 10-12 and as the instant case is a continuation of parent application 15/737,723 now U.S. Patent 11,414,657, there is no safe harbor protection and the method claims instantly recited would be obvious. Wherein the relevant claims of the two applications are not patentably distinct, when the claims at issue merely recited methods of administering therapeutically-effective amounts of the compositions claimed or means of making and no safe harbor exists.
Additionally, if a patent resulting from the instant claims was issued and transferred to an assignee different from the assignee holding the U.S. Patent 11,414,657, then two different assignees would hold a patent to the claimed invention of U.S. Patent 11,414,657, and thus improperly there would be possible harassment by multiple assignees.
Conclusion
No claims are allowed.
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/MARIA MARVICH/ Primary Examiner, Art Unit 1633
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