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 .
It is noted that the application claims a multitude of sequences. The instant office action is directed to the first claimed species of claim 1.
Specification
The disclosure is objected to because the structures on pages 16 and 17, for example, are not fully legible.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 requires for the saRNA to be “TMEM173-Pr-70-invAb-Se-m1” or “TMEM173-Pr-70-ml-emod51”. However, the specification does not clearly define what specific compound is required by “TMEM173-Pr-70-invAb-Se-m1” or “TMEM173-Pr-70-ml-emod51”. Without further defining structural elements, the metes and bounds of “TMEM173-Pr-70-invAb-Se-m1” or “TMEM173-Pr-70-ml-emod51” cannot be clearly ascertained.
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 1-19 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to any small activating RNA (saRNA) that upregulates the expression of TMEM173, wherein the saRNA comprises a sense strand that is at least 80% complementary to a target sequence selected from the group consisting of SEQ ID NOs: 2-15, wherein the antisense strand is 14-30 nucleotides in length; and to methods of delivering the saRNA.
The specification does not adequately describe the structure required for the saRNA to function as claimed. Claim 1 requires the presence of an antisense strand only and no other structural requirements to describe the genus of compounds. The dependent claims recite the addition of a sense strand and optional overhangs. Without further description of the structure required for the saRNA to function as claimed, one would not be able to readily recognize which compounds are necessarily included or excluded from the recited genus; and would not be able to recognize that applicant was in possession of the entire claimed genus at the time of filing.
The specification discloses that [0004] any short RNA which leads to up-regulation of the expression of a target gene by any mechanism is termed a short activating RNA or small activating RNA (saRNA).
The specification discloses that the saRNA can be single or double-stranded and 14-30 nucleotides in length [0019]. The saRNAs of instant claim 1 comprise an antisense strand that is 14-30 nucleotides in length that is at least 80% complementary to any one of SEQ ID NOs: 2-15. However, the saRNAs of the specification are duplexes that comprise an antisense strand that is fully complementary to the target sequence and a sense sequence that is the complement thereof; and comprising specific modifications and overhangs (Table 3, page 11).
The specification does not adequately describe the structure required for the function. The species of the specification are not representative of the entire claimed genus. The structure recited encompasses a large genus of dsRNAs that would not likely have the function of inhibiting the expression of any HAO1 gene. The dsRNA agent can be very long (i.e. 1,000 nucleotides) and comprise 15 contiguous nucleotides of instant SEQ ID NO: 669 in the antisense strand in a different portion than the double-stranded region and have no other sequence specificity to any specific HAO1 target sequence. The species disclosed in the specification of siRNAs that comprise SEQ ID NO: 669 are not representative of the entire claimed genus.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
To achieve the desired function, it appears that the structure is required to be a duplex that comprises an antisense strand that is fully complementary to the target sequence and a sense sequence that is the complement thereof. Desaulniers et al. (J.Med.Chem.2025,68,22650−22664) teach that short activating RNAs (saRNAs) are short duplex RNAs that activate genes in the nucleus of the cell (abstract). The saRNAs of Desaulniers et al. are duplexes with overhangs (Figure 1). Desaulniers et al. teach that like their predecessor, siRNAs, saRNA therapeutics will likely also require bespoke and thoughtful design employing novel chemical modifications to maximize their efficacy and outcome (page 22661). The instant claims are not limited to any static structure for the saRNA and are directed to broad delivery of unmodified saRNAs of varying structures, a genus of compounds that has not been adequately described in the specification.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for saRNA structures within the instant enormous genus that function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claims 15-19 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 upregulation of TMEM173 with specific saRNA duplexes of the specification, does not reasonably provide enablement for a method of upregulating TMEM173 via delivery of any saRNA of the instant claim breadth; and is not enabling for a method of treating any cancer, any solid tumor, or any hepatocellular carcinoma, pancreatic cancer, or ovarian cancer via upregulation of TMEM173 alone. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in a determination of lack of enablement include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)
The instant claims are directed to a method of delivering via any means any naked and unmodified saRNA with no specific structure other than the instantly recited antisense strand and the predictable outcome of upregulating TMEM or treating any cancer, any solid tumor, or any hepatocellular carcinoma, pancreatic cancer, or any ovarian cancer.
The specification demonstrates upregulation of TMEM173 mRNA with specific saRNA duplexes with specific sequences in vitro (Example 1). These duplexes are not commensurate in scope with the instantly recited saRNAs.
Additionally, with regards to the specific saRNAs of the instant specification, the specification is not enabling for broad systemic delivery of each naked and unmodified saRNA duplex and the predictable outcome of upregulating TMEM or treating any cancer, any solid tumor, or any hepatocellular carcinoma, pancreatic cancer, or any ovarian cancer in vivo.
Additionally, the specification does not draw an adequate nexus between upregulation of TMEM173 alone and the predictable outcome of treating any cancer, any solid tumor, or any hepatocellular carcinoma, pancreatic cancer, or any ovarian cancer in vivo, which encompasses an enormous genus of diseases that have not been shown to be reliant upon TMEM173 expression alone.
To achieve the desired function, it appears that the structure is required to be a duplex that comprises an antisense strand that is fully complementary to the target sequence and a sense sequence that is the complement thereof. Desaulniers et al. (J.Med.Chem.2025,68,22650−22664) teach that short activating RNAs (saRNAs) are short duplex RNAs that activate genes in the nucleus of the cell (abstract). The saRNAs of Desaulniers et al. are duplexes with overhangs (Figure 1). Desaulniers et al. teach that like their predecessor, siRNAs, saRNA therapeutics will likely also require bespoke and thoughtful design employing novel chemical modifications to maximize their efficacy and outcome (page 22661). The instant claims are not limited to any static structure for the saRNA and are directed to broad delivery of unmodified saRNAs of varying structures, a genus of compounds that has not been adequately described in the specification.
Additionally, there is no guidance in the specification as filed that teaches how to deliver the instantly recited genus of saRNAs and predictably treating the instant genus of diseases in vivo.
Although applicant has demonstrated TMEM173 upregulation in vitro via specific saRNAs, the specification is not enabled for upregulating TMEM173 or treating the instant breadth of diseases in vivo by the broadly recited methods, as delivery and effective action therein is known in the art to be unpredictable with regards to saRNAs. Activity in vitro is not predictable of the in vivo therapeutic effect in the in vivo complex environment.
Pandey et al. (Nano Research, 2024, 17(10): 8990−9002) teach: saRNA and siRNA have identical nucleotide size, charge, and chemical properties. Most of the delivery vectors from the last section have been developed for siRNA delivery and worked just as well for saRNA delivery. One difference to consider is the higher therapeutic dose required for saRNA (nM) compared to siRNA (pM to nM) [78]. Based on current literature, every delivery vector developed for siRNA has also worked for saRNA delivery. This means that the siRNA delivery field can also serve as a roadmap for the future of saRNA delivery (page 8995).
Pandey et al. (Nano Research, 2024, 17(10): 8990−9002) teach: As with other nucleotide therapeutics, delivery remains the most significant challenge. This fast translation has been enabled, in part, by using vectors developed for siRNA delivery, which has the same target location, the cytosol, and physical properties as siRNA. As expected, the most advanced vectors are lipid nanoparticles, which have had a large impact in siRNA and mRNA delivery. Despite the similarities between siRNA and saRNA, the latter currently requires a higher target dose. This will undoubtedly have an effect on the choice of the vector as more of a particular vector needs to reach the target tissue. This might exclude siRNA vectors that are on the upper end of the safe therapeutic window. On the other hand, the higher dose requirement might reduce off-target effects for saRNA and allow for the usage of less selective vectors for saRNA delivery (page 8998).
Fujita et al. (Int. J. Mol. Sci. 2015, 16, 5254-5270) teach that two types of small RNA molecules, small interfering RNAs (siRNAs) and microRNAs (miRNAs), have a central function in RNAi technology. The success of RNAi-based therapeutic delivery may be dependent upon uncovering a delivery route, sophisticated delivery carriers, and nucleic acid modifications (page 5254). Fujita et al. teach that the success of an RNAi-based therapy in clinical trials rests on careful selection of target genes and miRNAs. Moreover, we suggest that a delivery route, sophisticated delivery carriers, chemical modification, and modified RNAi platforms are needed to enhance RNAi effects in cancer cells (pages 5262-5263).
Friedrich et al. (BioDrugs (2022) 36:549–571) teach that still, the development of siRNA therapeutics faces several challenges and issues, including the definition of optimal siRNAs in terms of target, sequence, and chemical modifications, siRNA delivery to its intended site of action, and the absence of unspecific off-target effects (Abstract). Friedrich et al. teach that the use of short siRNA is preferred because longer siRNAs can provoke an inflammatory antiviral immune response (page 551).
Friedrich et al. teach: As a basic parameter, the GC content of an siRNA is addressed by algorithms and its range should be between ~30 and 60%. Too low GC content can lead to weak or unspecific binding, whereas too high GC content may impede unwinding by helicase and incorporation in the RISC complex. Between nucleotides 9 and 14, however, low GC content is important to increase RISC function during mRNA cleavage. Sequences that could lead to secondary structures in the sense or antisense stand must be avoided (e.g., internal repeats, palindromes, CCC or GGG sequences). A proper duplex formation is essential for functional siRNA. Additionally, sequences that contain single nucleotide polymorphisms, miRNA seed matches, and known toxic motifs must be avoided (page 552).
Friedrich et al. teach: The 5′-untranslated region (and 3′-untranslated region) of mRNA as well as sequences close to the start codon are not recommended as siRNA targets, as the binding of regulatory proteins in this area may impede RISC binding and thus the silencing effect. Rather, selecting regions in the open reading frame about 50–100 nucleotides downstream of the start codon is recommended. Furthermore, siRNAs closer to the start codon seem to be more efficient than those further downstream (page 552). Friedrich et al. is evidence as to the delivery challenges, as well as the fact that not any siRNA inhibitor of a target would result in the desired therapeutic effect.
As outlined above, it is well known that there is a high level of unpredictability in the saRNA/RNAi art for therapeutic in vivo applications and design. The scope of the claims in view of the specification as filed together do not reconcile the unpredictability in the art to enable one of skill in the art to make and/or use the claimed invention, namely a broad method of treating the instant breadth of diseases via broad systemic delivery of a broad genus of agents encompassing in vivo effects.
MPEP 2164.01
Any analysis of whether a particular claim is supported by the disclosure in an application requires a determination of whether that disclosure, when filed, contained sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention.
Also, MPEP 2164.01(a)
Given the teachings of the specification as discussed above, one skilled in the art could not predict a priori whether introduction of any saRNA of the instantly recited genus having no modifications and via any mode of delivery in vivo by the broadly disclosed methodologies of the instantly claimed invention, would result in successful treatment of the instant genus of diseases or upregulation of TMEM173. To practice the claimed invention, one of skill in the art would have to de novo determine; the stability of the molecule in vivo, delivery of the molecule to the whole organism, specificity to the target tissue in vivo, dosage and toxicity in vivo, and entry of the molecule into the cell in vivo and the effective action therein. Without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation (see MPEP 2164.01(a)).
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.
Claim(s) 1, 6, 12, and 14-16 is/are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by Khvorova et al. (US 8,090,542 B2).
Khvorova et al. teach a siRNA comprising a sense and an antisense strand, wherein each strand is 19 nucleotides in length and the antisense strand comprises 16/19 nucleotides that are identical to instant SEQ ID NO: 2 and therefore the antisense strand is at least 80% complementary to instant SEQ ID NO: 2 (instant claims 1 and 6). See search result #15 of the PE2E sequence search file titled “us-18-282-402-2.szlim40.rni” as follows:
RESULT 15
US-10-714-333C-97566
Sequence 97566, US/10714333C
Patent No. 8090542
GENERAL INFORMATION
APPLICANT: Dharmacon, Inc.
APPLICANT: Khvorova, Anastasia
APPLICANT: Reynolds, Angela
APPLICANT: Leake, Devin
APPLICANT: Marshall, William
APPLICANT: Scaringe, Stephen
TITLE OF INVENTION: Functional and Hyperfunctional siRNA
FILE REFERENCE: 13499US
CURRENT APPLICATION NUMBER: US/10/714,333C
CURRENT FILING DATE: 2003-11-14
PRIOR APPLICATION NUMBER: 60/502,050
PRIOR FILING DATE: 2003-09-10
PRIOR APPLICATION NUMBER: 60/426,137
PRIOR FILING DATE: 2002-11-14
NUMBER OF SEQ ID NOS: 1591911
SEQ ID NO 97566
LENGTH: 19
TYPE: DNA
ORGANISM: Homo sapiens
Query Match 74.7%; Score 14.2; Length 19;
Best Local Similarity 63.2%;
Matches 12; Conservative 4; Mismatches 3; Indels 0; Gaps 0;
Qy 1 GCAGATATCCGATGTAATA 19
Db 1 GCAGAUUUCAGAUGUAAGA 19
Khvorova et al. teach that the siRNA can have a 3’ overhang on the sense and/or antisense strand (column 9) (instant claims 3 and 8); and that the overhang can be UU (column 31)(instant claims 4 and 9); and that the overhang can be dTdT (column 31)(instant claim 10); and that the siRNA can comprise a 2’-O-methyl modification (column 7) (instant claim 12); and that the siRNA can be formulated into a composition with a pharmaceutically acceptable carrier (column 33)(instant claim 14); and that the siRNA can be delivered (instant claims 15 and 16).
Since Khvorova et al. teaches a compound that meets each of the instant structural limitations and a method of delivering the compound, the compound would necessarily achieve the recited outcome of up-regulating the expression of TMEM173 and increasing expression by at least 30%, absent evidence to the contrary. As stated in the MPEP (see MPEP 2112), something that is old does not become patentable upon the discovery of a new property.
Therefore, the instant invention is anticipated by Khvorova et al.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 102(a)(1) or (a)(2) as being anticipated by Saetrom et al. (US 2018/0305689 A1).
Saetrom et al. teach saRNAs for upregulating the expression of a target gene (abstract) and teach a saRNA wherein the sequence of the antisense strand comprises the sequence of instant SEQ ID NO: 81 and the sense sequence is the complement thereof (instant claims 1, 2, 5-7, and 11). Saetrom et al. teach that the target can be TMEM173 (page 68).
See the PE2E sequence search file titled “us-18-282-402-81.szlim40.rnpbm” as follows:
RESULT 7
US-15-568-046A-578104
Sequence 578104, US/15568046A
Publication No. US20180305689A1
GENERAL INFORMATION
APPLICANT: SAETROM, PAL
APPLICANT: STOVNER, ENDRE BAKKEN
TITLE OF INVENTION: SARNA COMPOSITIONS AND METHODS OF USE
FILE REFERENCE: 2058.1300US371
CURRENT APPLICATION NUMBER: US/15/568,046A
CURRENT FILING DATE: 2017-10-20
PRIOR APPLICATION NUMBER: PCT/GB2016/051116
PRIOR FILING DATE: 2016-04-21
PRIOR APPLICATION NUMBER: 62/150,892
PRIOR FILING DATE: 2015-04-22
PRIOR APPLICATION NUMBER: 62/150,893
PRIOR FILING DATE: 2015-04-22
PRIOR APPLICATION NUMBER: 62/150,897
PRIOR FILING DATE: 2015-04-22
PRIOR APPLICATION NUMBER: 62/150,895
PRIOR FILING DATE: 2015-04-22
PRIOR APPLICATION NUMBER: 62/150,900
PRIOR FILING DATE: 2015-04-22
PRIOR APPLICATION NUMBER: 62/150,904
PRIOR FILING DATE: 2015-04-22
PRIOR APPLICATION NUMBER: 62/150,908
PRIOR FILING DATE: 2015-04-22
NUMBER OF SEQ ID NOS: 2585259
SEQ ID NO 578104
LENGTH: 19
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
oligonucleotide
FEATURE:
OTHER INFORMATION: Antisense strand to SEQ ID NO: 578103
Query Match 90.5%; Score 19; Length 19;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 UUGUGGAGAAACCAAUCGU 20
|||||||||||||||||||
Db 1 UUGUGGAGAAACCAAUCGU 19
The saRNA of Saetrom et al. comprises instant SEQ ID NO: 34 as the antisense sequence and instant SEQ ID NO: 20 as the sense sequence (instant claims 2 and 7).
Saetrom et al. teach: [0083] In one embodiment, the antisense strand of a double-stranded saRNA has a 1-10 nucleotide overhang at the 3′ end and/or the 5′ end. In one embodiment, the antisense strand of a double-stranded saRNA has 1-4 nucleotide overhang at its 3′ end, or 1-2 nucleotide overhang at its 3′ end. In one embodiment, the sense strand of a double-stranded saRNA has a 1-10 nucleotide overhang at the 3′ end and/or the 5′ end. In one embodiment, the sense strand of a double-stranded saRNA has 1-4 nucleotide overhang at its 3′ end, or 1-2 nucleotide overhang at its 3′ end. In one embodiment, both the sense strand and the antisense strand of a double-stranded saRNA have 3′ overhangs. The 3′ overhangs may comprise one or more uracils, e.g., the sequences UU or UUU. In one embodiment, one or more of the nucleotides in the overhang is replaced with a nucleoside thiophosphate, wherein the internucleoside linkage is thiophosphate. In one embodiment, the overhang comprises one or more deoxyribonucleoside, e.g., the sequence dTdT or dTdTdT. In one embodiments, the overhang comprises the sequence dT*dT, wherein * is a thiophosphate internucleoside linkage (instant claims 3, 4, and 8-10).
When the saRNA of Saetrom et al. (that comprises instant SEQ ID NO: 34 as the antisense sequence and instant SEQ ID NO: 20 as the sense sequence) comprises a uu overhang, the saRNA comprises instant SEQ ID NOs: 48 and 73 (instant claims 5 and 11).
Saetrom et al. teach: [0123] In some embodiments, the saRNA of the present invention may comprise inverted deoxy abasic modifications on the passenger strand. The at least one inverted deoxy abasic modification may be on 5′ end, or 3′ end, or both ends of the passenger strand. The inverted deoxy basic modification may encourage preferential loading of the guide strand.
With regards to instant claim 13, the specification does not clearly set forth what structure is required for “TMEM173-Pr-70-invAb-Se-m1” or “TMEM173-Pr-70-ml-emod51”. Since Saetrom et al. teach the sequences of TMEM173-Pr-70 and teach incorporation of inverted deoxy abasic modifications and other modifications, the compound is considered to be anticipated by Saetrom et al.
Saetrom et al. teach: [0116] Nucleotides in the saRNAs of the present invention may comprise non-standard nucleotides, such as non-naturally occurring nucleotides or chemically synthesized nucleotides or deoxynucleotides. The saRNA of the present invention may include any useful modification, such as to the sugar, the nucleobase, or the internucleoside linkage (e.g. to a linking phosphate/to a phosphodiester linkage/to the phosphodiester backbone). One or more atoms of a pyrimidine nucleobase may be replaced or substituted with optionally substituted amino, optionally substituted thiol, optionally substituted alkyl (e.g., methyl or ethyl), or halo (e.g., chloro or fluoro). In certain embodiments, modifications (e.g., one or more modifications) are present in each of the sugar and the internucleoside linkage. Modifications according to the present invention may be modifications of ribonucleic acids (RNAs) to deoxyribonucleic acids (DNAs), threose nucleic acids (TNAs), glycol nucleic acids (GNAs), peptide nucleic acids (PNAs), locked nucleic acids (LNAs) or hybrids thereof. In a non-limiting example, the 2′-OH of U is substituted with 2′-OMe (instant claim 12).
Saetrom et al. teach: [0143] Pharmaceutical formulations may additionally comprise a pharmaceutically acceptable excipient (instant claim 14).
Saetrom et al. teach: [0290] In one embodiment, the saRNA described herein may be used to treat breast disorders such as breast neoplasia (e.g., breast cancer), breast cyst, breast disease, breast engorgement, breast hematoma, breast lump, Duct ectasia of breast, Hypertrophy of breast, Inverted nipple, Fissure of the nipple, Mammary myofibroblastoma, Mastitis, Mastodynia, Mondor's disease, Nonpuerperal mastitis, Pseudoangiomatous stromal hyperplasia, Ptosis (breasts), Subareolar abscess, Tuberous breasts, and Zuska's disease (instant claims 15-18) or pancreatic cancer [0329] (instant claim 19).
Since Saetrom et al. teaches a compound that meets each of the instant structural limitations and a method of delivering the compound to upregulate a target, the compound would necessarily achieve the recited outcome of up-regulating the expression of TMEM173 and increasing expression by at least 30%, absent evidence to the contrary. As stated in the MPEP (see MPEP 2112), something that is old does not become patentable upon the discovery of a new property.
Therefore, the instant invention is anticipated by Saetrom et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636