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 .
Application Status
The action is written in response to applicant’s correspondence received on 2/15/2024. Claims 20-32 are currently pending in the instant application.
Priority
The instant application claims priority to US Provisional Application 62/234,291, filed on 8/18/2021.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Hyperlink can be found on page 27, under the section “Example 1 – reducing expression of FAT10 in mouse hepatocyte cell line using anti-FAT10 ASO”.
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.
Claims 20-32 are 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.
Regarding claim 20, applicant recites “a composition comprising an antisense oligonucleotide (ASO) RNA therapeutic targeting FAT10 and a suitable carrier, wherein the ASO has at least 90% sequence identity to sequences set forth in SEQ ID NO: 3-5”. Here, applicant draws the claim to an antisense RNA therapeutic, however, the SEQ ID NOs provided recite DNA molecules. This is evidenced by the provided sequence listing wherein SEQ ID NO: 3-5s are provided as DNA sequences with a thymine nucleotide instead of an uracil nucleotide. It is unclear if the applicant intends to claim an RNA sequence for the antisense oligonucleotide, or a DNA sequence transcribed to RNA. Subsequent claims are rejected for being dependent on claim 20.
Amending claims to “…..wherein the ASO has at least 90% sequence identity to an RNA encoded by any of the nucleotide sequences set forth in SEQ ID Nos: 3-5.”
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.
Claims 20 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Williams et al. (US 2021/0199660 A1, published 7/1/2021).
Regarding claim 20 and 21, Williams teaches methods and compositions for determining biomarkers of breast cancer. Williams teaches the administration of a substrate, wherein the substrate is a bead (see paragraph 0017), and comprises a plurality of capture probes, wherein the capture probes comprises the capture domain and a spatial barcode (see paragraph 0012). Williams further teaches where the probes target specific genes with the spatial barcode domain (see paragraph 0012 and 0014) and presents SEQ ID NO: 744209 and 772267 in the sequence listings (See ABSS search results), which comprises a sequence that has 100% identity to the 20 nucleotide length of SEQ ID NO: 3 and 4, respectively.
As claims 20 and 21 are drawn to a composition claim, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent, see MPEP § 2112.01. The structure is taught by Williams, wherein Williams teaches a probe and spatial barcode which reads on an antisense oligonucleotide targeting FAT10 (SEQ ID NO: 744209 and 772267 ) and a substrate being a bead which reads on a carrier. As the structure is fully taught by Williams, the structure of being an inhibitor targeting FAT 10 is presumed to be inherent. Furthermore, one skilled in the art would recognize that the delivery of a probe and guiding sequence which hybridizes to a DNA segment within a cell would prevent other transcriptional elements from binding, therefore leading to inhibition.
In view of the foregoing, claims 20 and 21 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Williams.
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 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over West et al. (AU 2014201129 A1, published 03/20/2014) in view of Dhuri et al. (Antisense Oligonucleotide: An Emerging Area in Drug Discovery and Development, J. Clin. Med., Volume 9, Issue 6, all pages, published 6/26/2020), Katzmann et al. (Targeting RNA with Antisense Oligonucleotides and Small Interfering RNA in Dyslipidemias: JACC State-of-the-Art Review, JACC Journals, Volume 76, Number 5, pgs. 563-579, published 7/27/2020), and Jia et al. (The Role of FAT10 in Alcoholic Hepatitis Pathogenesis, Biomedicines, all pages, published 7/1/2020).
Regarding claim 20, West teaches methods and compositions for the treatment and diagnosis of bladder cancer. West teaches where in some embodiments, a method of treating cancer may comprise gene knockdown of one or more cancer associated sequences described herein (see paragraph 0192). Gene knockdown may be accomplished with a treatment such as a short DNA or RNA oligonucleotide with a sequence complementary to either an mRNA transcript or a gene. In some embodiments, the oligonucleotide used may be selected from RNase-H competent antisense (see paragraph 0192).
West teaches wherein the compositions can be formulated readily by combining the therapeutic with pharmaceutically acceptable carriers well known in the art (see paragraph 0233).
Regarding claim 22, West teaches a method of treating bladder cancer may comprise gene knockdown of one or more genes selected from…UBD…(see paragraph 0026), wherein said gene knockdown can be done with a composition presented as an antisense oligonucleotide (see paragraph 0192). West discloses UBD is also known as FAT10, as evidenced by Fig 2I of West.
Therefore, West teaches a composition comprising an antisense oligonucleotides and a pharmaceutically acceptable carrier targeting FAT10.
West does not teach where the antisense oligonucleotide has at least 90% sequence identity or fully comprises of the sequence set forth in SEQ ID NO: 3-5.
Regarding claim 20-21, Dhuri teaches antisense oligonucleotide discovery and design, wherein ASO bind sequences specifically to target RNA and modulate protein expression (see abstract). Dhuri teaches it has been well established that active ASOs are generally 15-20 nucleotides in length and can target complementary RNA by Watson-Crick base pairing without causing any significant off-target toxicity (see section 3 – Antisense Mechanism of Action). Therefore, one skilled in the art would routinely experiment with a sequence of interest to eventually arrive at any one of the claimed SEQ ID NOs: 3-5, absent evidence to the contrary.
Regarding claims 23-24, the combined arts of West and Dhuri does not teach where the RNA therapeutic is configured to provide liver specific reduction in FAT 10-levels (claim 22), the RNA therapeutic is conjugated to a GalNAc molecule (claim 23), or where the composition further comprises a PCSK9 inhibitor (claim 24).
Regarding claims 22-24, Katzmann teaches targeting the liver with antisense oligonucleotides. Katzmann teaches the recent development of adding N-acetyl galactosamine (GalNAc) to the RNA product (ASO or siRNA) represents a significant advance which facilitates the highly efficient liver-specific uptake of the drug, thereby allowing the desired pharmacodynamic effect to be achieved at markedly lower doses where the protein of interest is made principally or entirely by hepatocytes (see introduction).
Katzmann further teaches where small molecule drugs are recommended as the first-line therapy to lower LDL cholesterol however there is a counter-regulatory effect which limits their ability to lower LDL. This is because small molecule drugs can stimulate production of PCSK9, a hepatic protein that reduces LDL receptor activity and impairs LDL removal from circulation. Therefore, a new therapeutic approach to inhibit PCSk9 with monoclonal antibodies allows many patients with hypercholesterolemia to achieve unprecedented, very low levels of LDL-C (see introduction).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the teachings of West, Dhuri, and Katzmann to arrive at a composition comprising an ASO therapeutic targeting FAT10, and a suitable carrier, which is configured to provide liver specific reduction in FAT10 levels.
One would expect a reasonable chance of success as West discloses the use of ASOs to inhibit the list of as genes, wherein the ASO targets FAT10 or UBD-3. Furthermore, as evidenced by Dhuri and Katzmann, antisense oligonucleotides are a tested method of targeting RNA to modulate protein expression and the development of specific ASOs can be done through routine experimentation. Therefore, one skilled in the art would be able to design a 20-mer nucleotide sequence targeting the FAT10 gene in humans, which is 894 nucleotides in length, as represented by SEQ ID NO: 2, and arrive at a sequence that is identical to SEQ ID NOs: 3-5.
One would be motivated to do so as Katzmann discloses ASOs in a composition comprising GalNAc and PCSK9 inhibitors allows for effective treatment of chronic diseases such as atherosclerotic cardiovascular disease (see introduction). Katzmann also teaches where cellular uptake and the release of the drug into the cytoplasm represents a bottleneck in the clinical application of RNA-targeting drugs for decades (see section titled “Technologies for the delivery of RNA-targeting therapeutics). Therefore, the addition of GalNAc and PCSK9 inhibitors allow for enhanced liver-specific delivery (see abstract) and reduce the counter regulatory effects of PCSK9 (see introduction).
One would specifically be motivated to target the FAT10/UBD-3 gene as Jia teaches that FAT10 is essential to maintain the function of liver cell protein quality control and Mallory-Denk body (MDB) formation. FAT10 overexpression leads to balloon degeneration and MDB aggregation formation (see abstract), making it a target of ASO RNA therapeutics.
In view of the foregoing, claims 20-24 are rejected under 35 U.S.C. 103 as being prima facie obvious before the effective filing date.
Claims 25-32 are rejected under 35 U.S.C. 103 as being unpatentable over West et al. (AU 2014201129 A1, published 03/20/2014) in view of Dhuri et al. (Antisense Oligonucleotide: An Emerging Area in Drug Discovery and Development, J. Clin. Med., Volume 9, Issue 6, all pages, published 6/26/2020), Katzmann et al. (Targeting RNA with Antisense Oligonucleotides and Small Interfering RNA in Dyslipidemias: JACC State-of-the-Art Review, JACC Journals, Volume 76, Number 5, pgs. 563-579, published 7/27/2020), and Jia et al. (The Role of FAT10 in Alcoholic Hepatitis Pathogenesis, Biomedicines, all pages, published 7/1/2020).
Regarding claim 25, the composition of claim 20 are taught in the combined arts of West, Dhuri, and Katzmann, as described above. To review, the combined arts teach a composition comprising ASO, a carrier, a GalNAc molecule, a PCSK9 inhibitor, and a pharmaceutically acceptable carrier configured to provide liver specific reduction in FAT10 levels.
Regarding claim 25, Katzmann teaches a method for targeting patients with hypercholesterolemia to achieve unprecedented, very low levels of LDL-C with ASO/RNA drug therapeutics (see introduction).
Regarding claim 26, Katzmann teaches where such patients have heterozygous or homozygous familial hypercholesterolemia (see introduction).
Regarding claim 27 and 28, the combined arts of West, Dhuri, and Katzmann teach how one skilled in the art would arrive at an ASO which comprises a nucleotide sequence set forth in any of SEQ ID NOs: 3-5 that is configured to provide liver specific reduction in FAT10 levels, as described above.
Regarding claim 29, Katzmann teaches where the RNA therapeutic is conjugated to GalNAc in order to provide liver-specific delivery (see introduction).
Regarding claim 30 and 31, Katzmann teaches small molecule drugs (such as ASOs and siRNAs) are recommended as the first-line therapy to lower LDL cholesterol (see introduction) and conjugation with GalNAc allows for efficient delivery to the liver (see “Liver-specific delivery with GalNAc).
Regarding claim 32, Katzmann teaches where the composition further comprises a PCSK9 inhibitor to reduce the counter regulatory effects of PCSK9 produced by the liver (see introduction).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the claimed invention, to have combined the teachings of West, Dhuri, and Katzmann to arrive at a method which delivers a composition comprising an ASO therapeutic targeting FAT10, and a suitable carrier, which is configured to provide liver specific reduction in FAT10 levels, in order to treat familial hypercholesterolemia.
One would expect a reasonable chance of success as Katzmann teaches RNA based drugs have been tested in clinical settings to reduce triglycerides and/or cholestrol in participants (see section titled “clinical data” in Katzmann).
One would be motivated to do so as Katzmann discloses RNA based therapeutics in hepatocytes is emerging as a new and efficacious pharmacological strategy for patients at high risk for cardiovascular events (see conclusion of Katzmann). Furthermore, one would be motivated to target FAT10 or UBD-3 as Jia teaches that FAT10 is essential to maintain the function of liver cell protein quality control and Mallory-Denk body (MDB) formation. FAT10 overexpression leads to balloon degeneration and MDB aggregation formation (see abstract), making it a target of ASO RNA therapeutics.
In view of the foregoing, claims 25-32 are rejected under 35 U.S.C. 103 as being prima facie obvious, before the effective filing date.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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