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 .
Claim Status
Claims 1-12 are pending. Claims 1-12 are rejected.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The application is given the foreign priority date of June 8, 2023 for prior art analysis purposes .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/17/2024 was considered by the examiner. The submission is in compliance with the provisions of 37 CFR 1.97.
Drawings
Drawings have been considered and accepted by examiner.
Claim Rejections - 35 USC § 101
Claims 1-8 are rejected under 35 U.S.C. 101 because the claimed composition is a product of nature without any markedly different characteristics from any naturally occurring counterparts:
Laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. The courts have often described these
exceptions using other terms, including "physical phenomena," "scientific principles", "natural laws," and "products of nature." [MPEP 2106.04(c)]
Regarding claim 1, claim 1 recites a small-molecule peptide comprising of the sequence Tyr-Phe or Phe-Tyr, which is a product of nature. See the analysis below.
Step 1: Does the claim fall into a statutory category of invention?
Yes, the claim is directed to a composition of matter, which falls into a category of invention.
Step 2A: Is the claim directed to a law of nature, a natural phenomenon
(product of nature) or an abstract idea?
Yes, the claim is directed to a product of nature because the small-molecule peptide can be derived from Cytochrome b (Accession Number: Q8HHE1 · Q8HHE1_PAPAL). The mitochondrion in Pappogeomys alcorni (Alcorn's pocket gopher) encodes the 21 amino acid protein and positions 7-9 consist of Tyr-Phe. As for Phe-Tyr, the RloB domain-containing protein from the organism Bacteroides ovartus (Accession number: A0A642C174 A0A · A0A642C174_BACOV) comprises of the sequence at positions 20-21.
The markedly different characteristic analysis is part of Step 2A: Prong One. The
markedly different characteristic analysis compares the nature-based product limitation
to its naturally occurring counterpart in its natural state, the first step in the analysis is
to select the appropriate counterpart(s) to the nature-based product.
Step 2A Prong One: Does the claim recite an abstract idea, law of nature, or
natural phenomenon?
In the present case, the answer is yes because when a nature-based product is
derived from a naturally occurring thing, then the naturally occurring thing is the
counterpart. Section 2106.04 (b) recites:
When a law of nature or natural phenomenon is claimed as a physical product, the courts have often referred to the exception as a "product of nature". For example, the isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 580, 106 USPQ2d 1972, 1975 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). As explained in those decisions, products of nature are considered to be an exception because they tie up the use of naturally occurring things, but they have been labeled as both laws of nature and natural phenomena. See Myriad Genetics, Inc., 569 U.S. at 590-91, 106 USPQ2d at 1979 (claims to isolated DNA held ineligible because they claim “naturally occurring phenomena" and are "squarely within the law of nature exception")
Step 2A Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application?
Because the markedly different characteristics analysis is based on comparing the characteristics of the claimed nature-based product and its counterpart, the second step in the analysis is used to identify appropriate characteristics to compare. Appropriate characteristics must be possessed by the claimed product, because it is the claim that must define the invention to be patented. In the present case, each component found in nature is unmodified by a defining quantity like its application to MAFLD or MAFLD-related disorders such as hyperlipidemia or blood glucose regulation.
In regards to claim 2, Cytochrome b (Accession Number: Q8HHE1) from Alcorn's pocket gopher comprises of SEQ ID No:1 at positions 6-9.
In regards to claim 3, the RloB domain-containing protein from the organism Bacteroides ovartus (Accession number: A0A642C174 A0A · A0A642C174_BACOV) comprises of SEQ ID NO:2 at positions 18-21.
In regards to claim 4, an amino acid sequence that is two to four sequences, comprising of Tyr-Phe or Phe-Tyr is a naturally-derived fragment of either Cytochrome b (Accession Number: Q8HHE1) from an Alcorn's pocket gopher or the RloB domain-containing protein from the organism Bacteroides ovartus (Accession number: A0A642C174 A0A), respectively
In regards to claim 5, a small-molecule peptide that consists of SEQ ID No:1 is a naturally-derived fragment of Cytochrome b (Accession Number: Q8HHE1).
In regards to claim 6, a small-molecule peptide that consists of SEQ ID No:2 is a naturally-derived fragment of the RloB domain-containing protein from the organism Bacteroides ovartus (Accession number: A0A642C174 A0A).
In regards to claim 7, a small-molecule peptide that consists of Tyr-Phe is a product of nature derived from Cytochrome b from a Alcorn's pocket gopher (Accession Number: Q8HHE1).
In regards to claim 8, a small-molecule peptide that consists of Phe-Tyr is a product of nature derived from the RloB domain-containing protein from the organism Bacteroides ovartus (Accession number: A0A642C174 A0A).
Claim Rejections - 35 USC § 112
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 9-12 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 treating of MAFLD, hyperlipidemia, and blood glucose regulation where the treating does not include curing, does not reasonably provide enablement for the full scope of treating of MAFLD and all MAFLD-related disorders like cardiovascular diseases or obesity and preventing all MAFLD-related disorders like cardiovascular diseases or obesity. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The invention is a small-molecule peptide. Currently, the prior art does not support the whole scope of treating and prevention. Words of a claim must be given their ’plain meaning’ unless such meaning is inconsistent with the specifications [see MPEP 2111.01]. The accepted plain meaning of the word treating is to give medical care; to cure or heal (Cambridge Dictionary (2022). Treating. @CambridgeWords). However, the applicant’s invention is not enabled to cure MAFLD and all MAFLD-related diseases. For example, diabetes can be not be cured, but can attain complete remission if glucose levels return to non-diabetic [Joslin Education Team, pgh 3].
Joslin Education Team. (2020). Can Type 2 Diabetes Be Reversed? Joslin Diabetes Center.
The current prior art also does not support curing MAFLD. “Currently, there is no medication or method that can completely and immediately cure fatty liver disease [Section 3].
What medicine should be taken for fatty liver? (2025, January 25). Vinmec
Thus, the word ‘treating’ is not enabled because treating encompasses curing unless otherwise defined. Preventing MAFLD-related disorders is also not enabled because MAFLD-related diseases like cardiovascular disease cannot always be prevented. Eighty percent of cardiovascular diseases are preventable by healthy diet, physical activity, avoiding tobacco, and ‘knowing your numbers,’ but that means 20% are not.
World heart federation. (2023). CVD Prevention. World Heart Federation.
Therefore, not all MAFLD-related disorders can be enabled to preventing and the whole scope of treating.
Also, not all cardiovascular diseases, like hypertension, are MALFD or hyperlipidemia related. According to Nanna et al., “elevations in lipoprotein cholesterol levels may not confer additional (cardiovascular) risk in populations 75 or older” [pgh 1].
(Nanna, M., Peterson, E., & Navar, A. M. (2019, November 19). Hyperlipidemia not Associated with Cardiovascular Risk in Older Adults. Duke Health Referring Physicians)
Out of the other notable examples of MAFLD-related disorders the applicant has listed, obesity is also not enabled. Shahraz et al. explains “not all persons with obesity are at an increased risk of cardiovascular and metabolic diseases. Despite having high fat deposits, a specific group of people with metabolically healthy obesity (MHO) has been found, with preserved lipid and inflammatory profiles and normal blood pressure, unlike the metabolically unhealthy obesity (MUO) condition” [pgh 2].
(Shahraz, J., Joukar, F., Sheida, F., Yeganeh, S., Maroufizadeh, S., Baghaee, M., Naghipour, M., & Mansour-Ghanaei, F. (2025). Associations Between Body Mass Index (BMI) and Dyslipidemia: Results from the PERSIAN Guilan Cohort Study (PGCS). Obesity science & practice, 11(1), e70055.).
Thus, there is a lack of predictability that small-molecule peptides can cure or prevent all MAFLD-related disorders. The animal test done in the specifications was done on MAFLD-mode mice who have metabolic hyperlipidemia [0050]. The applicant aims to improve or prevent “liver-related disease, hyperlipidemia, and hyperlipidemia-related metabolic diseases (e.g. cardiovascular lesions)” [0051]. However, applicant’s invention is not enabled to treat all MAFLD-related disorders such as cardiovascular diseases and obesity. To be enabling, undue experimentation would be required to use the invention. Among the MAFLD-related disorders, applicant is enabled to treat hyperlipidemia [0050] and blood glucose regulation [0056], according to the specifications.
Regarding claim 12, applicant’s composition is not enabled to reduce body weight because as stated in claim 9’s rejection, obesity or excessive amount of body weight does not guarantee high lipid profiles. Since obesity is not always an MAFLD-related disorder, the applicant is not enabled to treat all MAFLD-related disorders.
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)(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 1 and 4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shen et al (CN112795613A: Published 2021; English Translation provided.).
Shen et al. discloses antidiabetic polypeptides derived from peony seed meal, with the main active ingredient being Tyr-Phe-Phe-Met, Phe-Phe-Phe-Met or Tyr-Tyr-Phe-Met to inhibit α-glucosidase [See Claims 2 and 3; Abstract; Table 1]. Shen et al. anticipates claim 1 because two out of three of the polypeptides Shen et al. claims comprise of the sequence Tyr-Phe.
In regards to claim 4, Tyr-Phe-Phe-Met and and Tyr-Tyr-Phe-Met are a four amino acid sequence. Thus, Shen et al, anticipates a two to four amino acid sequence comprising of the sequence Tyr-Phe.
Claims 1 and 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Held et al. (WO2003004604A2: Published 2003).
Held et al. claims an isolated polypeptide comprising a carboxy terminal amino acid sequence of a member selected from a group that contains the applicant’s sequence EWYF (SEQ ID NO: 576 AND 577) as a polypeptide that interacts with and binds to PDZ domains [see claim 71]. Thus, Held et al. anticipates a small-molecule peptide comprising of the sequence EWYF (claim 2) or YF (claim 1).
Claims 1, 3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Geng et al. (CN105085631A: Machine Translation Provided). Geng et al claim polypeptides capable of targeting the HER2 protein. Of these peptides, they claim SEQ ID NO: 19 for targeting HER2 albumen [ see claim 2] and SEQ ID NO:19 is a small molecule peptide with comprising of SEQ ID NO:2 (claim 3) and FY (claim 1).
Claims 1, 4, 8 and 11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Suzuki et al (JP6713981B2: Published 2020; English Translation Provided). Suzuki et al. present linear and cyclic dipeptides that act as lipase inhibitors. The dipeptides aim to treat obesity and diseases related thereto. While the claims are specific to cyclic dipeptides, including Cyclo(Phe-Tyr) [claim 1], the specifications also claim the linear dipeptide Phe-Tyr as an active ingredient in the lipase inhibitor [see spec bullet 22]. Thus, Suzuki et al. anticipates a small-molecule peptide comprising of Phe-Tyr.
Regarding claim 4, the dipeptide Phe-Tyr is composed of 2 amino acids [See spec bullet (22)].
Regarding claim 8, the amino acid sequence of the dipeptide is Phe-Tyr [See spec bullet (22)].
Regarding claim 11, Suzuki’s dipeptides are lipase inhibitors that meant for the “prevention or improvement of obesity or various disease such as diabetes, hyperlipidemia, hypertension, or arteriosclerosis” [see Abstract]. Since an artisan of ordinary skill, like the applicant, knows hyperlipidemia embodies high levels of lipids, treating hyperlipidemia translates to regulating lipids. Thus, Suzuki et al. anticipates using Phe-Tyr dipeptides for lipid regulation.
Therefore, the disclosures of Suzuki et al. anticipated the instantly claimed invention.
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.
Claims 9-10 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Shen et al., as previously applied to claims 1 and 4.
Shen et al.’s polypeptide sequences are hypoglycemics, also known to a person of ordinary as antidiabetic drugs [see Shen’s 0005]. It would have been prima facie obvious to an artisan of ordinary skill prior to the effective filing date to administer Shen et al’s 4-mers to treat and/or prevent MAFLD and MAFLD-related disorders because diabetes is a MAFLD-related disorder, as the applicant specifies [0011]. Under the principles of inherency, if a prior art device, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art device [see MPEP 2112.02].
In regards to claim 10, the title of the Shen et al’s invention categorizes the polypeptides as blood-sugar lowering [see 54]. It would have been prima facie obvious to apply Shen et al’s peptides to regulate blood sugar because a person of ordinary skill knows blood sugar is analogous to blood glucose.
In regards to claim 12, the same rejection used for claim 10 applies. The title of Shen’s invention is “Peony seed meal-sourced blood sugar lowering polypeptide and application thereof” [see (54)]. Thus, it would have been obvious to use Shen et al’s peptides as a method for reducing blood sugar by administering them.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al.
Wang, Y., Liu, Y., Gao, B., Yan, J., Cai, W., & Jiang, L. (2022). Untargeted Metabolomics Reveal Parenteral Nutrition-Associated Alterations in Pediatric Patients with Short Bowel Syndrome. Metabolites, 12(7), 600.
Wang et al. studied the metabolites of pediatric patients with short bowel syndrome (SBS) undergoing parenteral nutrition support. Long-term PN is accompanied by severe complications such as catheter-related blood stream infection (CRBSI) and intestinal failure-associated liver disease (IFALD). The presence of IFALD in SBS was associated with alterations of metabolites mainly classified as “amino acids, peptides, and analogues” and “benzene and derivatives” [Abstract]. One of the altered peptide metabolites was Tyr-Phe. Tyr-Phe is an upregulated end-product of metabolism in IFALD (Table 3). This prior art gives one of ordinary skill in the art sufficient motivation to experiment with the dipeptide Tyr-Phe as a method of treating liver diseases such as MAFLD because it is a metabolite seen in intestinal failure-associated liver disease and may have a correlation with liver health. It would have been obvious to try Tyr-Phe because there are only six types of amino acid, peptides and analogues that are metabolites in positive mode and seven in negative mode mass spectrometry [Figure 3C]. There is are a finite number of amino acid-based metabolites and a finite number of possibilities, either affecting liver disease, or not [see MPEP 2143].
Summary
Claims 1-12 are rejected under 35 USC 101. Claims 9-12 are rejected under 35 U.S.C. 112(a). Claims 9-11 are rejected under 35 U.S.C. 112(b). Claims 1-6, 8, and 11 are rejected under 35 USC 102. Claims 7, 9-10, and 12 are rejected under 35 USC 103.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SACHI JAUHARI whose telephone number is (571)272-3769. The examiner can normally be reached Mon-Fri 9-4.
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/SACHI JAUHARI/Examiner, Art Unit 1654
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654