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 .
Summary & Application Status
Claims 1- 20 are pending.
Claims 1- 20 are considered on the merits.
Claim 6 is objected.
Claims 1- 20 are rejected.
No Claims are allowed.
This action is written in response to applicant's correspondence received 2026 June 16. Claims 1- 20 are currently pending and under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant's amendments and arguments have been thoroughly reviewed but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Withdrawn Claim Objections
The objections of claims 1, 11, and 16 of the office action dated 2026 April 28 have been corrected by applicant’s amendment.
Claim Objections
Claim 6 is objected to because of the following informalities: Claim 6 recites “wherein the therapeutic nucleic acid is siRNA having a nucleotide sequence of SEQ ID NO 35.” This is wrong because there appears to be a grammatical error; the article “an” is missing (highlighted below). The claim is currently interpreted as “wherein the therapeutic nucleic acid is an siRNA having a nucleotide sequence of SEQ ID NO 35.”
Claim 8 recites “The method of claim 1, wherein the subject is a vertebrate comprising human”. This claim is objected to for lack of conciseness. Since all humans are vertebrates, then it is unnecessary and redundant to recite “vertebrate comprising human”. The claim instead should recite “wherein the subject is a human”. Claim 18 is objected to for the same reasons.
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.
Claims 4 and 13 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 claims 4 and 13, the claim recites “wherein the therapeutic nucleic acid comprises… or a construct of clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated protein 9 (Cas9).“ This is unclear because a nucleic acid (by itself) may not comprise a protein.
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.
Claims 11- 14, and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shi (Shi et al. Biochem Biophys Res Commun. 2017 Sep 16;491(2):349-354.).
Claim Interpretation
Claim 11 recites the clause “a therapeutic nucleic acid configured to reduce hepatic G protein-coupled receptor 110 (GPR110) expression thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCD1) expression in the liver of a subject…” This examiner has not found any prior art indicating hepatic GPR110 is any different from any other GPR110. Therefore, any molecular interaction based on the structure of GPR110 is synonymous with the structure of hepatic GPR110 and vice versa. Furthermore, the limitation “… to reduce hepatic G protein-coupled receptor 110 (GPR110) expression thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCD1) expression in the liver of a subject in need thereof for treating non-alcoholic fatty liver disease (NAFLD), or conditions and symptoms associated therewith” is intended use that does not further modify the structure of the “pharmaceutical composition comprising a therapeutic nucleic acid.” Furthermore, the clause “thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCD1) expression in the liver of a subject” is simply functional language that describes a natural biological pathway (scientific truism) and provides no further guidance toward the structure of the “therapeutic nucleic acid” of the instant claim. Therefore, Claim 11 is essentially, a nucleic acid.
Regarding Claim 11, Shi, teaches the use of siRNA to knockdown (silence) GPR110, “the GPR110-RNAi cells were transfected by small interfering RNA… the siRNA was designed and synthesized by Santa Cruz Biotechnology” (section 1.4 Cell Culture).
Therefore, Shi teaches all of the elements of claim 11.
Claim 12 depends on Claim 11. Shi, teaches siRNA nucleic acids capable of gene silencing GPR110 as cited above. Claim 12 recites “wherein the therapeutic nucleic acids are capable of gene silencing of GPR110.” Therefore, Shi teaches all of the elements of Claim 12.
Claim 13 depends on Claim 11. Shi teaches the embodiment “small interfering RNA (siRNA)” as cited above.”
Claim 14 depends on Claim 11. Shi teaches a siRNA targeted (specific) to GPR110 as cited above. Furthermore, the current record provides no indication that hepatic GPR110 is any different from any other GPR110 as noted above. Claim 14, recites, “wherein the therapeutic nucleic acid is hepatic GPR110-specific antisense oligonucleotides (ASOs).” Therefore, Shi teaches all of the elements of Claim 14.
Claims 18 depends on Claim 11. In the same paragraph as noted above (section 1.4 Cell Culture), Shi teaches the subject is human cells and therefore the targeted GPR110 is human, “Human glioblastoma cell lines U87 cells were obtained from ATCC (the American Type Culture Collection, Manassas, VA, USA). U87-GPR110 cells were generated by transient transfection of pcDNA-GPR110 plasmid into cells, while the GPR110-RNAi cells were transfected by small interfering RNA…” Therefore, Shi teaches all of the elements of Claim 18.
Claim 17 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shi (Shi et al. Biochem Biophys Res Commun. 2017 Sep 16;491(2):349-354.), as evidenced by Papatheodoridi (Papatheodoridi et al. Curr Pharm Des. 2018;24(38):4574-4586.), Umbro (Umbro et al. Biomedicines 2021, 9, 1370.), and Wójcik-Cichy (Wójcik-Cichy et al. Clinical and Experimental Hepatology. 2018;4(1):1-6.).
Claims 17 depends on Claim 11. The limitations of Claim 17 simply states a scientific truisms and is merely a recitation of the symptoms of NAFLD. A subject having NAFLD will inherently have the symptoms associated therewith. Papatheodoridi describes the following symptoms: hepatic steatosis, and chronic noncommunicable diseases (NCDs), non-alcoholic steatohepatitis (NASH) with fibrosis, cirrhosis and hepatocellular carcinoma (HCC), wherein the NCDs comprise type 2 diabetes mellitus (T2DM). (Abstract, Introduction, 1st paragraph; page 4575, 1st column, 3rd paragraph, Table 1). Umbro teaches, the following symptoms: chronic noncommunicable diseases (NCDs), cardiovascular disease (CVD), and chronic kidney disease (CKD). (Abstract). Wójcik-Cichy teaches , the following symptoms: chronic noncommunicable diseases (NCDs),(CVD). (Abstract). Claim 17 recites, “wherein the conditions or symptoms associated with the NAFLD comprise hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, hepatocellular carcinoma (HCC), type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), hypertriglyceridemia, atherosclerosis, and chronic kidney disease (CKD).”
Response to Arguments
Applicant's arguments filed 2026 June 16 have been fully considered but they are not persuasive.
Regarding claim 11, applicant has amended claim 11 to further define that "A pharmaceutical composition comprising a therapeutic nucleic acid configured to reduce hepatic G protein-coupled receptor 110 (GPR110) expression thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCDI) expression in the liver of a subject.” The applicant argues the amendment separates the instant claim from Shi whom, according to applicant “merely teaches the use of siRNA to knockdown (silence) GPR110.” The applicant points to [0054]- [0056] of the specification to make the point “global knockout of SCD1 “leads to harmful consequences such as inhibition of fat mobilization in adipose tissues” a liver specific knockdown is better via targeting liver specific GPR110.
These arguments are not persuasive because, as cited in the previous office action, there is nothing in the prior art nor the instant application that distinguishes liver GPR110 from any other GPR110. Neither paragraphs [0054]- [0056], nor does any working example within the specification provide any evidence otherwise. Furthermore, the liver targeting of the instant oligonucleotide is more likely due to the GlcNAc moiety conjugated to the nucleic acid rather than the sequence of the nucleic acid as evidenced by Debacker (Debacker et al. Delivery of Oligonucleotides to the Liver with GalNAc: From Research to Registered Therapeutic Drug. Mol Ther. 2020 Aug 5;28(8):1759-1771.) “Targeted delivery of oligonucleotides to liver hepatocytes using N-acetylgalactosamine (GalNAc) conjugates that bind to the asialoglycoprotein receptor has become a breakthrough approach in the therapeutic oligonucleotide field.” This is further admitted in the instant specification Example 3 “two N-acetylgalactaosamine (GalNAc) (sic) conjugated antisense oligonucleotides (ASO- GPR110s)… Chronic treatment of either ASO-GPR110s only lowered the hepatic, but not renal, GPR110 mRNA (FIGs. 5B and 6B) and protein (FIG. 6C) levels. It is due to the fact that liver hepatocytes abundantly and specifically express the asialoglycoprotein receptor that binds and uptakes circulating glycosylated oligonucleotides via receptor-mediated endocytosis.”[0077].
Furthermore, except for the clause “configured to reduce … G protein-coupled receptor 110 (GPR110) expression” the current amendment is simply intended use language and continues to provide no further modification toward the structure of the pharmaceutical composition.
In response to applicant's argument that "thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCDI) expression in the liver of a subject,” a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim.
Furthermore, paragraphs [0054]- [0056] merely prophetically describe the benefits of liver-localized knockdown of SCD1. These sections do not point toward any data.
Regarding claims 12-14, and 18, applicant argues the claimed hepatic GPR110 is different from other GPR110s by stating “the claimed therapeutic nucleic acid is specifically designed to target hepatic GPR110, instead of global knockout of GPR110, suggesting that hepatic GPR110is different from other GPR110at least from the specific gene silencing perspective.” And further points to Example 9 of the specification. Example 9 describes four siRNAs complementary to GPR110. The siRNAs were tested against four hepatic cell lines (HepG2, Hep3B, Huh7, and L-O2,) but not any non-hepatic cell lines. Therefore, the example does not provide any evidence that the siRNA are liver specific over any other tissue.
Regarding claim 17, applicant argues “None of these [references] evidences provides any teaching or motivation to a person of ordinary skill in the art to remedy the deficiency of Shi or to anticipate the specific therapeutic” qualities cited. As noted previously, the limitations of claim 17 are merely recitations of symptoms of NAFLD and do not modify the structure of the pharmaceutical composition. Therefore, no further reference is necessary to overcome the claim.
For the reasons listed above, the applicant's arguments filed 2026 June 16 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 8, and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Yang et al. World J Gastroenterol. 2021 Feb 28;27(8):677-691.) as applied to claim 1 above, and further in view of Ma (Ma et al. Am J Cancer Res. 2017 Mar 1;7(3):433-447.), and Liu (Liu et al. Med Sci Monit. 2018 Jul 27;24:5216-5224.).
Regarding Claim 1, Yang provides a review of G protein-coupled receptors (GPCRs) as targets in the treatment (therapy) of nonalcoholic fatty liver disease (NAFLD), "This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment. Overall, understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD." (Abstract). Yang teaches the treatment of conditions and symptoms of NAFLD, and the administration of a therapeutic composition, "intraperitoneal or oral administration of a peptide hormone metabolitin that binds to GPRC6A significantly ameliorated NAFLD symptoms ... " (page 683, first paragraph). Furthermore, Yang teaches treatment via GPCR knockdown, "Knockdown of GPR137 in HepG2 cells resulted in cell cycle arrest and cell apoptosis ... " (Table 1). Yang further teaches NAFLD treatment with nucleic acids via GPCR shRNA knockdown, "Inhibiting GPR91 expression by lentivirus harboring shRNA reduced succinate-mediated HSC [Hepatic stellate cell] activation." (page 681, third paragraph). Additionally, Yang teaches modulation of GPCR expression in the liver, "TGR5 is widely expressed in different nonparenchymal liver cells, altering expression in response to BAs like lithocholic acid." (page 679, last paragraph). Yang notes the object of NAFLD treatments" ... peptide-YY and GLP-1, can be modulated through GPCRs to regulate insulin secretion in obese subjects" (page 680, 1st paragraph).
Furthermore, Yang teaches the downregulation of SCD1 via GPCRs, “Treatment with docosahexaenoic acid, … inhibited lipid droplets by interacting with GPR40 in primary hepatocytes via reduced expression of lipogenic enzymes, such as … stearoyl-CoA desaturase-1” (Page 683, Conclusion, 5th paragraph). Yang further describes SCD1 inhibition via GPCR pathways “Gut hormones, such as … GLP-1, can be modulated through GPCRs … For instance, SCFAs can stimulate incretin hormone GLP-1 secretion via GPR43… GLP-1 can regulate hepatic steatosis … accompanying the reduction in the mRNA and protein expression of … stearoyl-CoA desaturase-1…” (page 680, 1st paragraph). Furthermore, even in the absence of Yang’s teachings that GPCR inhibition simultaneously inhibits SCD1 expression, inhibition of SCD1 expression is simply a biochemical functional result (a scientific truism) of GPR110’s downregulation and provides no meaningful steps or limitations to the instant claim nor provide additional structural insight to the nucleic acid of the claim.
Therefore, in consideration of the crux of the instant application (as described in the office action dated 2026 April 28), Yang teaches the following elements of Claim 1: "A method for treating non-alcoholic fatty liver disease (NAFLD), or conditions and symptoms associated therewith, the method comprising administering to a subject in need thereof a composition comprising a therapeutic nucleic acid to reduce hepatic G protein-coupled receptor ... expression thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCD1) expression in the liver of the subject."
However, Yang does not teach the GPCR 110 (GPR110), but Yang does suggest targeting GPCRs in general for treatment of NAFLD disease, "Overall, GPCRs and their regulating factors provide potential pharmacological targets for NAFLD treatment." (Page 684, Conclusion, 1st paragraph). Furthermore, Yang provides motivation to target GPCRs in the treatment of NAFLD, "There are several advantages to targeting GPCRs to treat NAFLD compared with other NAFLD therapeutics ... GPCRs are implicated in the development and progression of NAFLD, including lipid metabolism, proinflammation, and fibrosis. Therefore, targeting GPCR can be applied to different stages of NAFLD therapy, ranging from simple steatosis to NASH." (Page 684, Conclusion, 1st paragraph).
Ma teaches GPR110 is a GPCR expressed in the liver, "GPR110 was an adhesion G protein coupled receptor. Analysis of the expression pattern of GPR110 in mice displayed that GPR110 was expressed highly in liver ... " (Abstract). Ma further teaches that GPCRs are responsible for some cancers, including hepatocellular carcinoma (HCC) and HCC may lead to nonalcoholic steatohepatitis (NASH), "In recent years, since aberrant expressions of several adhesion-GPCR molecules have been identified in various human cancers, they have been closely associated with cancer development.;" "HCC has clearly defined etiological factors, including viral hepatitis, nonalcoholic steatohepatitis (NASH), alcoholic liver disease, and cirrhosis." (Introduction, 2nd and l51 paragraphs). Ma further teaches GPR110 knockdown, "Based on a GPR110 knockout mouse model... " (Abstract).
Therefore, Ma teaches the GPR110 of Claim 1 not taught by Yang.
However, Ma does not teach the therapeutic nucleic acids targeting GPR110, but Ma does suggest targeting GPR110 as a means of therapy for liver disease, "In light of our studies, a combination of targeting GPR110 and IL-6/STAT3 activation may profoundly improve liver cirrhosis therapies" (page 445, last paragraph).
Liu teaches GPR110 is a GPCR, "G protein-coupled receptor 110 (GPR110) belongs to the subfamily of the adhesion G protein-coupled receptors (GPCRs)." (Background, line 1) and further teaches that targeting GPR110 expression is a potential method of treatment for disease, "This study aimed to examine the expression level of GPR110 and determine whether the expression of GPR110 was correlated with aggressive clinicopathological characteristics and prognosis of osteosarcoma." (Background, line 4). In the course of investigating potential treatments, Liu teaches using therapeutic nucleic acids, specifically siRNA knockdown, to reduce GPR110 expression, "... proliferation, migration, and invasion capacity of SAOS-2 and K7M2 cells were enhanced by GPR110-overexpression compared with knockdown cells." and "The transfection efficiency of pcDNA3.l-GPR110 plasmids and GPR110 siRNA in SAOS-2 and K7M2 cells was tested by western blot." (Page 5022, column 1, l51 paragraph).
Therefore, Liu teaches “a therapeutic nucleic acids configured to reduce hepatic GPR110 expression” of Claim 1 not taught by Ma.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) at the time of filing of the instant application to have taken Yang's "method for treating non-alcoholic fatty liver disease (NAFLD), or conditions and symptoms associated therewith, the method comprising administering to a subject in need thereof a composition comprising a therapeutic nucleic acid to reduce hepatic G protein-coupled receptor ... expression thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCD1) expression in the liver of the subject." and instead substituted GPR110 for the GPCR to arrive at the claimed invention because Yang, Ma, and Liu each provided motivation to do so.
A PHOSITA would have known of Yang's method. Similarly, A PHOSITA would have been familiar with Yang's suggestion and motivation to target GPCRs for treating NAFLD. Furthermore, Yang's suggestion in combination with their own motivation as a person in the same field of endeavor to search out other potential GPCR targets for the treatment of NAFLD. GPR110 was a known GPCR and Ma and Liu both identified GPR110 as a viable target for treatment of disease. Ma specifically identified GPR110 as a target for liver disease and further identified GPR110 knockdown as a means of therapy. Liu's disease therapy specifically targeted GPR110 via siRNA (nucleic acid) silencing. A PHOSITA in the field of NAFLD treatment would obviously consider the suggestion of Yang to explore other GPCR targets in treating NAFLD leading them to Ma's liver GPR110 knockdown. This would ultimately lead to Liu's nucleic acids-based targeting of GPR110. A PHOSITA would have a reasonable expectation of success in treating NAFLD via targeting GPCRs (Yang's method) by silencing GPR110 in the liver (as demonstrated by Ma) with the therapeutic nucleic acids of Liu.
Regarding Claim 2, Yang, Ma and Liu teach all of the elements of Claim 1. Furthermore, Yang teaches methods of administering a therapeutic composition including injection and oral administration as cited above.
Regarding Claim 8, Yang, Ma, and Liu teach all of the elements of Claim 1. Furthermore, Yang teaches several NAFLD subjects for potential treatment including clinical trial treatment in humans “For example, T2D patients aged 20 or older orally received 75 mg of GPR119 agonist DS-8500a daily for 4 wk…” (page 680, last paragraph).
Yang therefore teaches all of the elements of Claim 8, “wherein the subject is a vertebrate comprising human.”
Regarding Claims 9 and 10, Yang, Ma, and Liu teach all of the elements of Claim 1. Furthermore, Yang teaches NAFLD can be treated by delivering a lentivirus as cited above.
Yang therefore teaches all of the elements of Claim 9, “further comprising delivering the therapeutic nucleic acid via a viral vector.;” and also teaches the embodiment “lentiviral vector,” therefore teaching all of the elements of Claim 10, “wherein the viral vector comprises adenoviral vector, adeno-associated viral vector, retroviral vector, or lentiviral vector.”
Claim(s) 3 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Yang et al. World J Gastroenterol. 2021 Feb 28;27(8):677-691.), and Ma (Ma et al. Am J Cancer Res. 2017 Mar 1;7(3):433-447.), and Liu (Liu et al. Med Sci Monit. 2018 Jul 27;24:5216-5224.), and as applied to claim 1 above, and further evidenced by Mocellin (Mocellin et al. J Transl Med. 2004 Nov 22;2(1):39.) and Watts (Watts et al. J Pathol. 2012 Jan;226(2):365-79.).
Regarding Claim 3, Yang, Ma and Liu teach all of the elements of Claim 1. In particular, Ma teaches the GPCR GPR110. Furthermore, Yang teaches treatment via GPCR knockdown as cited above. Mocellin teaches gene knockdown and gene silencing are synonymous by using the two terms interchangeably, "The effect of RNAi should be quantified at both the mRNA and the protein level. The knockdown ... ," and "Although RNAi generally occurs within 24 h of transfection, both onset and duration of RNAi depend on the turnover rate of the protein of interest, as well as the rate of dilution and longevity of the siRNAs. The duration of gene silencing can also be modified ... " (page 5, column 1, last paragraph, and column 2 1st paragraph).
Furthermore, Watts discusses the basics of RNAi and explains RNAi is necessarily antisense to the nucleic acid sequence of interest, "the modulation of gene expression by nucleic acids has become a routine ... a target RNA is chosen based on a hypothesis about its physiological significance; a complementary oligonucleotide is synthesized; ... Single-stranded antisense oligonucleotides (ASOs) and RNA interference (RNAi) share their fundamental principle: an oligonucleotide binds a target RNA through Watson-Crick base pairing." (page 365, column 1, paragraphs 1, 2; column 2, l51 paragraph).
Since Yang teaches treatment via RNAi, specifically shRNA, and in light of Watts' explanation that RNAi is complimentary (that is specific) to gene of interest (GPR110), Yang therefore teaches all of the elements of Claim 3, "wherein the therapeutic nucleic acids is capable of gene silencing of the hepatic GPR110."
Regarding Claim 4, Yang, Ma and Liu teach all of the elements of Claim 1 and 3. Furthermore, Yang teaches treatment via RNAi, specifically shRNA, as cited above.
Since Yang teaches the embodiment "short-hairpin RNA (shRNA)," Yang therefore teaches all of the elements of Claim 4, "wherein the therapeutic nucleic acid comprises a small interfering RNA (siRNA), short-hairpin RNA (shRNA), micro-RNA (miRNA), or a construct of clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated protein 9 (Cas9)."
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Yang et al. World J Gastroenterol. 2021 Feb 28;27(8):677-691.), and Ma (Ma et al. Am J Cancer Res. 2017 Mar 1;7(3):433-447.), and Liu (Liu et al. Med Sci Monit. 2018 Jul 27;24:5216-5224.), and as applied to claim 1 above, and further evidenced by Watts (Watts et al. J Pathol. 2012 Jan;226(2):365-79.).
Regarding Claim 5, Yang, Ma and Liu teach all of the elements of Claim 1. Furthermore, Yang teaches treatment via RNAi, specifically shRNA, as cited above. Watts discusses the basics of RNAi and explains RNAi is necessarily antisense to the nucleic acid sequence of interest, "the modulation of gene expression by nucleic acids has become a routine ... a target RNA is chosen based on a hypothesis about its physiological significance; a complementary oligonucleotide is synthesized; ... Single-stranded antisense oligonucleotides (ASOs) and RNA interference (RNAi) share their fundamental principle: an oligonucleotide binds a target RNA through Watson-Crick base pairing." (page 365, column 1, paragraphs 1, 2; column 2, 1st paragraph).
Since Yang teaches treatment via RNAi, specifically shRNA, and in light of Watts' explanation that RNAi is complimentary (that is specific) to gene of interest (GPR110), Yang therefore teaches all of the elements of Claim 5, "wherein the therapeutic nucleic acid is hepatic GPR110-specific antisense oligonucleotides (ASOs)."
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Yang et al. World J Gastroenterol. 2021 Feb 28;27(8):677-691.), and Ma (Ma et al. Am J Cancer Res. 2017 Mar 1;7(3):433-447.), and Liu (Liu et al. Med Sci Monit. 2018 Jul 27;24:5216-5224.), and as applied to claim 1 above, and further in view of Rao (Rao et al. siRNA vs. shRNA: similarities and differences. Adv Drug Deliv Rev. 2009 Jul 25;61(9):746-59.), and Davicioni (Davicioni US-20180216197-Al), and further evidenced by Watts (Watts et al. J Pathol. 2012 Jan;226(2):365-79.).
Regarding Claim 6, Yang, Ma and Liu teach all of the elements of Claim 1. Furthermore, Yang teaches treatment via RNAi, specifically shRNA. In addition to Watts' teachings above, Watts teaches "Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression." (Abstract). Additionally, Rao discusses the ease of interchangeability between shRNA and siRNA techniques for treatment of disease, "Methods of mediating the RNAi effect involve small interfering RNA (siRNA), short hairpin RNA (shRNA) and bifunctional shRNA. The simplicity of siRNA manufacturing and transient nature of the effect per dose are optimally suited for certain medical disorders (i.e. viral injections)." (Abstract). Therefore Yang, Ma, and Liu in light of Watts and Rao teach the elements of Claim 6, "wherein the therapeutic nucleic acid is [an] siRNA."
However, Yang, Ma, Liu, Watts, and Rao do not teach the siRNA having a sequence of SEQ ID No 35.
Davicioni teaches the SEQ ID No 1492 (Table 13, page 110). The instant application's SEQ ID No 35 matches 100% of its 23 nucleotides, with no mismatches to SEQ ID No 1492's 53 nt. Davicioni teaches "methods, systems and kits ... provide expression-based analysis of biomarkers" (Abstract). They teach the use of SEQ ID No 1492 in a related field of endeavor as the instant application, "measuring levels of expression in the biological sample of a plurality of genes selected from Table 3, Table 5, Table 13 or SEQ ID Nos: 1-4050" (Claim 1), where the gene corresponding to SEQ ID No 1492 is GPR110. Davicioni further clarifies, "detecting the presence or expression level in the biological sample for a plurality of targets selected from the group consisting of ... GPR110" ([0013]).
It would have been obvious to a person having ordinary skill in the art (PHOSITA) at the time of filing of the instant application to have taken the combined method taught by Yang, Ma, and Liu, "method for treating non-alcoholic fatty liver disease (NAFLD), conditions and symptoms associated therewith comprising administering to a subject a composition comprising a therapeutic nucleic acid to reduce hepatic G protein-coupled receptor 110 (GPR110) expression in liver of the subject, wherein the therapeutic nucleic acids is an siRNA" and substituted Davicioni's SEQ ID No 1492 for the therapeutic nucleic acid having a nucleotide sequence of SEQ ID NOs 35 to arrive at the claimed invention because it would have been obvious to try SEQ ID No 35 from a finite number of identified, predictable solutions, with a reasonable expectation of success.
As recited above, Yang, Ma, and Liu together in light of Watts and Rao teach all of the elements of "a method for treating non-alcoholic fatty liver disease (NAFLD), conditions and symptoms associated therewith comprising administering to a subject a composition comprising a therapeutic nucleic acid to reduce hepatic G protein-coupled receptor 110 (GPR110) expression in liver of the subject, wherein the therapeutic nucleic acid is an siRNAs," and therefore a PHOSITA would be knowledgeable of the teachings. Furthermore, as stated above, this same PHOSITA in the field of endeavor of treating NAFLD via GPR110 expression would necessarily look to particular siRNA sequences to treat NAFLD by down regulating GPR110. Inevitably, the PHOSITA would be led to GPR110 gene sequences, including Davicioni's GPR110 partial gene sequence matching SEQ ID No 1492.
Therefore Yang, Ma, Liu, and Davicioni in light of Watts and Rao teach all of the elements of Claim 6, "wherein the therapeutic nucleic acid is an siRNA having a nucleotide sequence of SEQ ID NO: 35."
Claims 7 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Yang (Yang et al. World J Gastroenterol. 2021 Feb 28;27(8):677-691.), and further in view of Ma (Ma et al. Am J Cancer Res. 2017 Mar 1;7(3):433-447.), and Liu (Liu et al. Med Sci Monit. 2018 Jul 27;24:5216-5224.) as applied to claims 1 and 11 above, and further in view of Papatheodoridi (Papatheodoridi et al. Curr Pharm Des. 2018;24(38):4574-4586.), Umbro (Umbro et al. Biomedicines 2021, 9, 1370.), and Wójcik-Cichy (Wójcik-Cichy et al. Clinical and Experimental Hepatology. 2018;4(1):1-6.).
Regarding Claim 7, Yang, Ma and Liu teach all of the elements of Claim 1. Furthermore, Yang, Ma, and Liu teach the instant claim. This instant claim simply states scientific truisms. The instant claim is merely a recitation of the symptoms of NAFLD, and each symptom claimed is known in the prior art. A subject having NAFLD will inherently have the symptoms associated therewith.
Papatheodoridi teaches the following symptoms: hepatic steatosis, and chronic noncommunicable diseases (NCDs), non-alcoholic steatohepatitis (NASH) with fibrosis, cirrhosis and hepatocellular carcinoma (HCC), wherein the NCDs comprise type 2 diabetes mellitus (T2DM). (Abstract, Introduction, 1st paragraph; page 4575, 1st column, 3rd paragraph, Table 1).
Umbro teaches the following symptoms: chronic noncommunicable diseases (NCDs), cardiovascular disease (CVD), and chronic kidney disease (CKD). (Abstract).
Wójcik-Cichy teaches , the following symptoms: chronic noncommunicable diseases (NCDs),
Yang, Ma, and Liu in light of Papatheodoridi, Umbro, and Wójcik-Cichy therefore teach all of the elements of Claim 7, “wherein the conditions or symptoms associated with the NAFLD comprise hepatic steatosis, fibrosis, cirrhosis, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), hypertriglyceridemia, atherosclerosis, and chronic kidney disease (CKD).”
Regarding Claim 11, Yang provides a review of G protein-coupled receptors (GPCRs) as targets in the treatment (therapy) of nonalcoholic fatty liver disease (NAFLD), “This review summarizes the current findings regarding the role of GPCRs in the development and progression of NAFLD and describes some preclinical and clinical studies of GPCR-mediated treatment. Overall, understanding GPCR-mediated signaling in liver disease may provide new therapeutic options for NAFLD.” (Abstract). Yang further suggests targeting GPCRs in general for treatment of NAFLD disease, “Overall, GPCRs and their regulating factors provide potential pharmacological targets for NAFLD treatment.” (Page 684, Conclusion, 1st paragraph). Yang further teaches the treatment of conditions and symptoms of NAFLD, and the administration of a therapeutic composition, “Intraperitoneal or oral administration of a peptide hormone metabolitin that binds to GPRC6A significantly ameliorated NAFLD symptoms…” (page 683, first paragraph). Yang further teaches NAFLD treatment and compositions with nucleic acids via GPCR shRNA knockdown, “Inhibiting GPR91 expression by lentivirus harboring shRNA reduced succinate-mediated HSC activation.” (page 681, third paragraph). Furthermore, Yang teaches treatment and compositions via GPCR knockdown, “Knockdown of GPR137 in HepG2 cells resulted in cell cycle arrest and cell apoptosis…” (Table 1). Additionally, Yang teaches modulation of GPCR expression in the liver, “TGR5 is widely expressed in different nonparenchymal liver cells, altering expression in response to BAs like lithocholic acid.” (page 679, last paragraph). Yang notes the object of NAFLD treatments and compositions “… peptide-YY and GLP-1, can be modulated through GPCRs to regulate insulin secretion in obese subjects”. (page 680, 1st paragraph),
Furthermore, Yang teaches the downregulation of SCD1 via GPCRs, “Treatment with docosahexaenoic acid, … inhibited lipid droplets by interacting with GPR40 in primary hepatocytes via reduced expression of lipogenic enzymes, such as … stearoyl-CoA desaturase-1” (Page 683, Conclusion, 5th paragraph). Yang further describes SCD1 inhibition via GPCR pathways “Gut hormones, such as … GLP-1, can be modulated through GPCRs … For instance, SCFAs can stimulate incretin hormone GLP-1 secretion via GPR43… GLP-1 can regulate hepatic steatosis … accompanying the reduction in the mRNA and protein expression of … stearoyl-CoA desaturase-1…” (page 680, 1st paragraph). Furthermore, even in the absence of Yang’s teachings, inhibition of SCD1 expression is simply a biochemical functional result (a scientific truism) of GPR110’s downregulation and provides no meaningful steps or limitations to the instant claim nor provide additional structural insight to the nucleic acid of the claim.
Therefore, in consideration of the crux of the instant application and the claim interpretation mentioned above, taken together Yang teaches the following elements of Claim 11: “A pharmaceutical composition comprising a therapeutic nucleic acid configured to reduce hepatic G protein-coupled receptor … expression thereby downregulating liver-specific stearoyl-coA desaturase 1 (SCD1) expression in the liver of a subject in need thereof for treating non-alcoholic fatty liver disease (NAFLD), or conditions and symptoms associated therewith.”
However, Yang does not teach the GPCR 110 (GPR110). But Yang does suggest targeting GPCRs in general for treatment of NAFLD disease, “Overall, GPCRs and their regulating factors provide potential pharmacological targets for NAFLD treatment.” (Page 684, Conclusion, 1st paragraph). Furthermore, Yang provides motivation to target GPCRs in the treatment of NAFLD, “There are several advantages to targeting GPCRs to treat NAFLD compared with other NAFLD therapeutics… GPCRs are implicated in the development and progression of NAFLD, including lipid metabolism, proinflammation, and fibrosis. Therefore, targeting GPCR can be applied to different stages of NAFLD therapy, ranging from simple steatosis to NASH.” (Page 684, Conclusion, 1st paragraph).
Ma teaches GPR110 is a GPCR expressed in the liver, “GPR110 was an adhesion G protein-coupled receptor. Analysis of the expression pattern of Gpr110 in mice displayed that Gpr110 was expressed highly in liver...” (Abstract) and further teaches that GPCRs are responsible for some cancers, including hepatocellular carcinoma (HCC) and HCC may lead to nonalcoholic steatohepatitis (NASH), “In recent years, since aberrant expressions of several adhesion-GPCR molecules have been identified in various human cancers, they have been closely associated with cancer development.,” “HCC has clearly defined etiological factors, including viral hepatitis, nonalcoholic steatohepatitis (NASH), alcoholic liver disease, and cirrhosis.” (Introduction, 2nd and 1st paragraphs). Ma further teaches GPR110 knockdown, “Based on a Gpr110 knockout mouse model…” (Abstract).
Therefore, Ma teaches the GPR110 of Claim 1 not taught by Yang.
However, Ma does not teach the therapeutic nucleic acids targeting GPR110, but Ma does suggests targeting GPR110 as a means of therapy for liver disease, “In light of our studies, a combination of targeting GPR110 and IL-6/STAT3 activation may profoundly improve liver cirrhosis therapies” (page 445 last paragraph).
Liu teaches GPR110 is a GPCR, “G protein-coupled receptor 110 (GPR110) belongs to the subfamily of the adhesion G protein-coupled receptors (GPCRs).” (Background, line 1) and further teaches that targeting GPR110 expression is a potential method of treatment for disease, “This study aimed to examine the expression level of GPR110 and determine whether the expression of GPR110 was correlated with aggressive clinicopathological characteristics and prognosis of osteosarcoma.” (Background, line 4). In the course of investigating potential treatments, Liu teaches using therapeutic nucleic acids, specifically siRNA knockdown, to reduce GPR110 expression, “… proliferation, migration, and invasion capacity of SAOS-2 and K7M2 cells were enhanced by GPR110-overexpression compared with knockdown cells.” and “The transfection efficiency of pcDNA3.1-GPR110 plasmids and GPR110-siRNA in SAOS-2 and K7M2 cells was tested by western blot.” (Page 5022, column 1, 1st paragraph).
Therefore, Liu teaches “a therapeutic nucleic acids configured to reduce hepatic GPR110 expression” of Claim 1 not taught by Ma.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) at the time of filing of the instant application to have taken Yang’s “pharmaceutical composition comprising a therapeutic nucleic acid to reduce hepatic G protein-coupled receptor … expression in liver of a subject in need thereof for treating non-alcoholic fatty liver disease (NAFLD), or conditions and symptoms associated therewith” and instead substituted GPR110 for the GPCR to arrive at the claimed invention because Yang, Ma, and Liu each provided motivation to do so.
A PHOSITA would have known of Yang’s “pharmaceutical composition comprising therapeutic nucleic acids to reduce G protein-coupled receptor … expression in liver of a subject in need thereof for treating non-alcoholic fatty liver disease (NAFLD), conditions and symptoms associated therewith.” Similarly, A PHOSITA would have been familiar with Yang’s suggestion and motivation (noted above) to target GPCRs for treating NAFLD. Furthermore, Yang’s suggestion in combination with their own motivation as a person in the same field of endeavor to search out other potential GPCR targets for the treatment of NAFLD. GPR110 was a known GPCR and Ma and Liu both identified GRP110 as a viable target for treatment of disease. Ma specifically identified GPR110 as a target for liver disease and further identified GPR110 knockdown as a means of therapy. A PHOSITA would takes Ma’s following suggestion toward Yang and Liu “In light of our studies, a combination of targeting GPR110 and IL-6/STAT3 activation may profoundly improve liver cirrhosis therapies.” Liu’s disease therapy specifically targeted GPR110 via siRNA (nucleic acid) silencing. A PHOSITA in the field of NAFLD treatment would obviously consider the suggestion of Yang to explore other GPCR targets in treating NAFLD leading them to Ma’s liver GPR110 knockdown. This would ultimately lead to Liu’s nucleic acids-based targeting of GPR110. A PHOSITA would have a reasonable expectation of success in developing a pharmaceutical composition of nucleic acids for treating NAFLD via targeting GPCRs (Yang’s composition) by silencing GPR110 in the liver (as demonstrated by Ma) with the therapeutic nucleic acids of Liu.
Regarding Claim 16, Yang, Ma, and Liu teach all of the elements of Claim 11. Furthermore, Yang teaches a pharmaceutical composition of nucleic acids administered via injection and oral administration as cited above.
Since Yang teaches the embodiment “[intravenous] injection and oral administration,” Yang therefore teaches all of the elements of Claim 16, “wherein the pharmaceutical composition is formulated for intravenous injection, subcutaneous injection, or oral administration.”
Regarding Claim 19 and 20, Yang, Ma, and Liu teach all of the elements of Claim 11. Furthermore, Yang teaches a pharmaceutical composition of nucleic acids to treat NAFLD with a lentivirus as cited above.
Yang therefore teaches all of the elements of Claim 19, “further comprising a viral vector;” and also teaches the embodiment “lentiviral vector,” therefore teaching all of the elements of Claim 20, “wherein the viral vector comprises adenoviral vector, adeno-associated viral vector, retroviral vector, or lentiviral vector.”
Regarding Claim 15, Yang, Ma, and Liu teach all of the elements of Claim 11. Furthermore, Yang teaches a pharmaceutical composition of nucleic acids, specifically shRNA. In addition to Watts’ teachings above, Watts teaches “Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are the two most widely used strategies for silencing gene expression.” (Abstract). Additionally, Rao discusses the ease of interchangeability between shRNA and siRNA techniques for treatment of disease, “Methods of mediating the RNAi effect involve small interfering RNA (siRNA), short hairpin RNA (shRNA) and bi-functional shRNA. The simplicity of siRNA manufacturing and transient nature of the effect per dose are optimally suited for certain medical disorders (i.e. viral injections).” (Abstract). Therefore, Yang and Liu in light of Watts and Rao teach the elements of Claim 15, “wherein the therapeutic nucleic acids are siRNAs.”
However, Yang, Liu, Watts, and Rao do not teach the siRNA having a sequence of SEQ ID No 35.
Davicioni teaches the instant SEQ ID No 35, referred to as SEQ ID No 1492 (Table 13, page 110). The instant SEQ ID No 35 matches 100% of its 23 nucleotides, with no mismatches to SEQ ID No 1492’s 53 nt. Davicioni teaches “methods, systems and kits … provide expression-based analysis of biomarkers” (Abstract). They teach the use of SEQ ID No 1492 in a related field of endeavor as the instant application, “measuring levels of expression in the biological sample of a plurality of genes selected from Table 3, Table 5, Table 13 or SEQ ID Nos: 1-4050” (Claim 1), where the gene corresponding to SEQ ID No 1492 is GPR110. Davicioni further clarifies, “detecting the presence or expression level in the biological sample for a plurality of targets selected from the group consisting of … GPR110” ([0013]).
It would have been obvious to a person having ordinary skill in the art (PHOSITA) at the time of filing of the instant application to have taken the combined pharmaceutical composition of nucleic acids taught by Yang and Liu, “A pharmaceutical composition comprising therapeutic nucleic acids to reduce G protein-coupled receptor 110 (GPR110) expression in liver of a subject in need thereof for treating non-alcoholic fatty liver disease (NAFLD), conditions and symptoms associated therewith” and substituted Davicioni’s SEQ ID No 1492 for the therapeutic nucleic acids having a nucleotide sequence of SEQ ID NOs 35 to arrive at the claimed invention because it would have been obvious to try SEQ ID No 35 from a finite number of identified, predictable solutions, with a reasonable expectation of success.
As recited above, Yang, Ma, and Liu together in light of Watts and Rao teach all of the elements of “a pharmaceutical composition comprising therapeutic nucleic acids to reduce G protein-coupled receptor 110 (GPR110) expression in liver of a subject in need thereof for treating non-alcoholic fatty liver disease (NAFLD), conditions and symptoms associated therewith, wherein the therapeutic nucleic acids are siRNAs,” and therefore a PHOSITA would be knowledgeable of the teachings. Furthermore, as stated above, this same PHOSITA in the field of endeavor of treating NAFLD via GPR110 expression would necessarily look to particular siRNA sequences to treat NAFLD by down regulating GPR110. Inevitably, the PHOSITA would be led to GPR110 gene sequences, including Davicioni’s GPR110 partial gene sequence matching SEQ ID No 1492.
Therefore Yang, Liu, and Davicioni in light of Watts and Rao teach all of the elements of Claim 15, “wherein the therapeutic nucleic acids are siRNAs each having a nucleotide sequence of SEQ ID NOs: 35.”
Response to Arguments
Applicant's arguments filed 2026 June 16 have been fully considered but they are not persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Regarding claims 1, 2, 4, 8-11, 13, 16, and 18-20, applicant argues “Yang is a review article of 20+ GPCRs but none of them is GPR110… Therefore, a person of ordinary skill in the art would not take Yang as a starting point.” The applicant further cites reasons why Yang, in the absence of the other references cited in the rejection, is insufficient to reject the claims as above. Similarly, the applicant cites reasons why Ma, and Liu, in the absence of the other references cited in the rejection, is insufficient to reject the claims as above.
The applicant further argues “the present application provides working examples of specific gene silencing of human hepatic GPR110 mRNA which shows liver-specific SCD1 downregulation leading to therapeutic efficacy in NAFLD treatment.”
These arguments are not persuasive because, the applicant does not point to where in the specification they are referring, this examiner assumes the previously mentioned Example 9 and paragraphs [0054]- [0056]. As stated previously, these sections are not persuasive.
The applicant further argues “the present application provides the selection criteria when designing the RNA sequence for gene silencing of human GPR110 mRNA” and points to paragraph [0104] which describes the siRNAs of Example 9 discussed earlier.
These arguments are not persuasive because, the selection criteria cited in the specification is well known in the art as exemplified in the cited references (see the rejections claim 5, 6 of the office action dated 2026 April 28), Yang, Mocellin, Rao, and particularly Watts.
The applicant further argues “surprising effects of inhibiting liver-specific SCD1 expression on improving liver fibrosis and steatosis in NAFLD subjects through the inhibition of GPR110 mRNA expression.”
These arguments are not persuasive because, again, the applicant does not point to what data in the specification they are referring. Furthermore, the applicant does not compare their results against prior art as necessitated by the MPEP to successfully argue “surprising effects (unexpected results)” (see MPEP 2145).
Regarding claim 11, the applicant amended the claim to read such that the therapeutic nucleic acid is “configured to reduce hepatic GPR110 expression thereby downregulating liver-specific SCDl1 expression in the liver of the subject for treating NAFLD or its associated conditions and symptoms” and further argues that “Yang in view of Ma and Liu fails to teach or suggest the claimed therapeutic nucleic acid.” The applicant further asserts their argument for all dependent claims.
These arguments are not persuasive because, as cited above, there is nothing in the prior art nor the instant application that distinguishes liver GPR110 from any other GPR110.
Regarding claims 3 and 12, the applicant argues that in light of their above cited amendment, the combination of Yang, Ma, Liu, and Mocellin “fails to provide an explicit teaching or motivation to inhibit the liver-specific SCD1 expression via specific gene silencing of hepatic GPR110 mRNA expression for treatment of NAFLD.”
These arguments are not persuasive because, as admitted by the applicant, “SCD 1 inhibition is known to be a therapeutic strategy for the treatment of metabolic syndrome” [0054]. Therefore, a PHOSITA would have known of this strategy and applied it as described in the instant rejection above.
Furthermore, except for the clause “configured to reduce … G protein-coupled receptor 110 (GPR110) expression” the current amendment is simply intended use language and continues to provide no further modification toward the steps of the method or structure of the pharmaceutical composition. Furthermore, as described in the instant rejection above, even in the absence of Yang, Ma, Liu, and Mocellin’s combined teachings, the simultaneous inhibition of SCD1 expression is simply a biochemical functional result (a scientific truism) of GPR110’s downregulation and provides no meaningful steps or limitations to the instant claim nor provide additional structural insight to the nucleic acid of the claim.
Regarding claims 5 and 14, the Applicant argues that they “disagrees with the allegation that Yang in view of Ma and Liu teach all the elements of claim 1, at least by virtue of the foregoing remarks and present amendments.”
These arguments are not persuasive for all of the same reasons cited above in the instant rejections and analysis of the instant amendment.
The applicant further cites reasons why Watts, in the absence of the other references cited in the rejection, is insufficient to reject the claims as above.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
The applicant further asserts “the present application provides examples of hepatic GPR110-specific ASOs (ASO-GPR110s)… in example 3 (also see examples 4-6 of the specification as filed).”
These arguments are not persuasive for all of the same reasons cited above.
Regarding claims 6 and 15, the applicant argues that in light of their above cited amendment, the combination of Yang, Ma, Liu, Watts, Rao and Davicioni fails to “teach all the elements of claim 1 [and claims 6 and 15]” and specifically cites Rao’s failure to remedy deficiency of Yang, Ma, and Liu in regard to the instant amendment.
These arguments are not persuasive for all of the same reasons cited above.
The applicant further recites the combination of references do not teach the instant SEQ ID NO 35 because “SEQ ID NO: 35 as it targets the 5' UTR of the human hepatic GPR110 mRNA which is not commonly selected in the field of siRNA gene silencing… [and] is not just simply derivable from looking at the Davicioni's SEQ ID No 1492.”
These arguments are not persuasive because the argument fails to consider the totality of the rejection analysis. Furthermore, simply because a target may not be common does not equate to its avoidance.
Regarding claims 7 and 17, the applicant argues that in light of their above cited amendment, the combination of Yang, Ma, Liu, Papatheodoridi, Umbro, and Wojcik-Cichy fails to teach all the elements of claims 1 and 11, and claims 7 and 17 indicating reasons cited previously. The Applicant specifically argues “the claimed pharmaceutical composition … is structurally or chemically different than the combined therapeutic agent derived from the combination.”
These arguments are not persuasive for all of the same reasons cited above. Furthermore, the Applicant provides no structural or chemical data as why the claimed pharmaceutical composition is “structurally or chemically different” from the referenced combination.
Regarding claims 8 and 10, the applicant argues claims 8 and 10 should be allowed by virtue of their previous arguments regarding claim 1 from which claim 8 and 10 depend.
These arguments are not persuasive for all of the same reasons cited above.
Inventorship
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
For the reasons listed above, the applicant's arguments filed 2026 June 16 have been fully considered but they are not persuasive.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AARON DUREL WARD whose telephone number is (571)272-8495. The examiner can normally be reached Monday to Thursday 8:00AM 6:00PM.
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/AARON DUREL WARD/ Examiner, Art Unit 1636
/NEIL P HAMMELL/ Supervisory Patent Examiner, Art Unit 1636
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