DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Amendment
Claims 1-6, 8-9, and 18 are pending
Claims 5-6 remain withdrawn
Claims 1-4, 8-9, and 18 are under examination.
Claim 1 is currently amended.
Examiner of Record has Changed
The Examiner of Record has changed from Randall O. Winston to Shubo (Joe) Zhou.
Claim Interpretation
Applicant has amended claim 1 to require that the composition comprises a pharmaceutically acceptable ester, salt, or amide of an aqueous botanical extract.
Examiner notes
That “pharmaceutically acceptable” has been defined in paragraph 0103 as “compounds, materials, compositions, and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings.”
That “pharmaceutically acceptable salt” has been defined in paragraph 0107 as “refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention.”
A pharmaceutically acceptable salt or amide has not been defined.
However, it is well known in the art that plants naturally have esters like (triglycerides, diglycerides, monoglycerides, and phospholipids). Moreover, these extracts are known to have insulin/diabetic properties. (See Cohen et al. US 2003/0190323 A1 at claim 1). Additionally, Chapal (WO2013072522 A1) teaches that chicoric/chlorogenic acid (natural ester) has insulin impacting properties.Therefore, a pharmaceutically acceptable ester would be no different than the natural esters already available in plant extracts.
Examiner Note
A review of applicant’s specification provides no disclosure identifying a specific constituent, phytochemical, or defined subcomponent of a plant extract as being responsible for upregulation of IRS2. Moreover, there is no disclosure of such a constituent, phytochemical, or defined subcomponent of a plant extract having the ability to provide the claimed Insulin Equivalents required by claim 1.
Response to Arguments
Applicant's arguments filed on 4/14/2026 have been fully considered but they are not persuasive.
Applicant argues that their amendment of an ester of an extract does not naturally exist.
This is not correct – see modified rejections below showing that natural extracts have esters.
The remaining rejections have been amended to address new limitations on the application of a pharmaceutically acceptable ester, salt, or amide on the claims.
With respect to the 112b, applicant argues that “insulin equivalent units” is definite because the control conditions like cell type and culture conditions are disclosed.
Applicant should amend the claim by the cell type and culture conditions if the example in the specification is to be limiting. Applicant’s argument is mostly we provided an example and that should be sufficient. As this measurement is made up by the applicant and not an art recognized testing protocol it would be unclear to what it means without the conditions directing someone of ordinary skill in the art.
Claim Rejections - 35 USC § 112
Indefiniteness
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.
Claims 1-4, 8-9, and 18 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 pre-AIA the applicant regards as the invention.
The currently amended claims now link a pharmaceutically acceptable ester, salt, or amide of an aqueous extract to upregulating IRS2 at 1X10^4 Insulin units in 1 milliliter.
First, it is unclear if the entire extract is to be an ester, salt, or amide or just a subcomponent of the extract. It is unclear how an entire plant or botanical extract can be in an ester, amide, or salt form. This is confusing as a review of applicant’s specification provides no disclosure identifying a specific constituent, phytochemical, or defined subcomponent of a plant extract as being responsible for upregulation of IRS2. There seems only to be a discussion on the testing of the whole extract leading to the confusion.
Second, even if the ester, salt, or amide claim language was limited to only subcomponents of an extract, this is still an issue as applicant’s definition of “insulin equivalent units” seems only to be tied towards improvement of the whole extract on a cell line. It is unclear how the insulin equivalent units would or could be measured in relation to a specific ester, salt, or amide of the extract.
Finally, a screen capture is below of the page in the specification which provides more information about the meaning of the phrase “Insulin Equivalent units.”
The specification further states that one “Insulin Equivalent unit” is the minimum amount of material necessary to increase growth of IRS2 overproducing test cells by 1% compared to control. This definition does not limit the cell type, the culture conditions, or the form of insulin used for the assay. It is well-understood in the art that insulin signaling pathways are high-regulated pathway that are influenced by several factors. Different cell types respond to insulin differently (see Patel et 2008 2:4, p.188-205 for example). Culture conditions can dramatically affect how a cell respond to insulin, such as concentration of glucose in the growth medium or whether the cells were serum-starved prior to initiating the experiment. For example, De Nigris 2015 (Cardiovascular Diabetology 14: 114) report that high glucose in the growth medium impaired insulin signaling endothelial cells. Additionally, there are many different forms of insulin that are manufactured today that have different characteristics including different half-lives and potencies (see Donnor T, Sarkar S. Insulin- Pharmacology, Therapeutic Regimens and Principles of Intensive Insulin Therapy. [Updated 2023 Feb 15]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278938/).
Given these potential points of variability which can influence the meaning of one “Insulin Equivalent unit,” the metes and bounds of the claims cannot be determined.
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Lack of Written Description
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-4, 8-9, and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant’s claims are now amended to have an ester, salt, or amide of a botanical extract that provides 1X10^4 Insulin equivalent units. These extracts are not from any specific plant but reference plant families that are diverse (The claimed plant families cover nearly 100,000 plant species). There are no specific examples of esters, amides, or salts from any of these species disclosed in the specification nor is there any requires structure/function relationship that ties applicant’s immense genus together.
Moreover, Shehadeh et al, teaches that many years after applicant’s filing date that research into effective antidiabetic drugs from plant materials/extracts is continuous and challenging. (See abstract). “This review highlighted the scientific evidence of the plant-derived secondary metabo-lites as potential multi-target antidiabetic agents. They can modulate enzymes, proteins, signaling pathways, cell proliferation, inflammatory mediators, gene transcription and expression. Numerous
compounds are promising antidiabetic agents; however, large scale anti-diabetic evaluation is needed. Therefore, it is important to advocate further research to validate and optimize targets, animal models, toxicity, efficacy, pharmacoki-netic studies and clinical trials for multi-target hypoglycemic therapy.” (See conclusion).
Even in the case of claim 4, which specifies that the extract is from Cichorium endivia var. latifolium, written description is lacking, because the there is no description as to what ester, amide, or salt subcomponent of that botanical extract causes the upregulating IRS2 function.
Additionally, in the indefiniteness rejection above, it makes clear that the meaning of Insulin Equivalent units is indefinite as the definition provided in the specification does not set forth all the required parameters to make the determination of “Insulin Equivalent units” present in the composition such that the assay result would not vary significantly as the parameters are changed (See indefiniteness rejection above).
The instant disclosure describes in Table 2 some natural products that have insulin like activity from species including endive, lettuce, and garden bean.
These descriptions are insufficient, because they fail to describe the unlimited genus of any compound that increases IRS2 function.
Given the broad scope of the claimed genus, the lack of working examples and the failure to describe the structures required to confer the claimed function, one of skill in the art would not have recognized that Applicant was in possession of the claimed genus at the time of filing.
Claim Rejections - 35 USC § 112 (enablement)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 8-9, and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Breadth of the claims
Applicant’s claims are now amended to have an ester, salt, or amide of a botanical extract that provides 1X10^4 Insulin equivalent units. These extracts are not from any specific plant but reference plant families that are diverse (The claimed plant families cover nearly 100,000 plant species). There are no specific examples of esters, amides, or salts from any of these species disclosed in the specification nor is there any requires structure/function relationship that ties applicant’s immense genus together.
State of the prior art
Shehadeh et al, teaches that many years after applicant’s filing date that research into effective antidiabetic drugs from plant materials/extracts is continuous and challenging. (See abstract). “This review highlighted the scientific evidence of the plant-derived secondary metabo-lites as potential multi-target antidiabetic agents. They can modulate enzymes, proteins, signaling pathways, cell proliferation, inflammatory mediators, gene transcription and expression. Numerous compounds are promising antidiabetic agents; however, large scale anti-diabetic evaluation is needed. Therefore, it is important to advocate further research to validate and optimize targets, animal models, toxicity, efficacy, pharmacokinetic studies and clinical trials for multi-target hypoglycemic therapy.” (See conclusion).
Amount of direction provided by the inventor and existence of working examples
A review of applicant’s specification provides no disclosure identifying a specific constituent, phytochemical, or defined subcomponent of a plant extract as being responsible for upregulation of IRS2. Moreover, there is no disclosure of such a constituent, phytochemical, or defined subcomponent of a plant extract having the ability to provide the claimed Insulin Equivalents required by claim 1.
It would requires undue experimentation to evaluate the 100,000 plant species for every subcomponent/metabolite ester, amide, or salt to see if it would impact IRS-2. Moreover, you would need to find a subcomponent that provided the claimed level of insulin units.
Examiner note: Seen in the 102 rejection below it seems like after the filing date chlorogenic acid was recognized to have IRS-2 upregulating impact as claimed. So, applicant was not enabled at the time of filing for this species to perform the claimed function. This is confirmed by the fact that applicant’s specification discloses chlorogenic acid but not as the extract but an additional supplement or vitamin. (See paragraph 0096).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4, 7-9 and 18 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claim(s) 1-4, 7-9 and 18 is/are directed to a natural phenomenon (i.e., a law of nature and a product of nature-e.g. step 1 (MPEP 2106.03)). The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial (i.e. do not recite additional elements/steps that integrate the exception into a practical application and/or do not recite additional elements that amount to significant more than the exception of the claimed naturally-occurring ingredients-e.g. step 2A2 (MPEP 2106.04(d) and 2B (MPEP 2106.5)) – i.e., as drafted, the cited claims read upon a product of nature for the following reasons:
Examiner note: There is no evidence that applicant synthesized or altered any subcomponent of an extract to be in an ester, salt, or amide form. It is understood by the office that these components must be a part of the plant natural extract components. As described above, esters naturally are present in plant extracts.
See 102 rejection below for evidence that natural esters can upregulate IRS-2.
Claims 1-4, 7-9 and 18 are drawn to a salt, amide, or ester of a biological extract that upregulates IRS-2 as disclosed within Applicant’s specification in paragraph 0045 and [0084] whereas page 2 last paragraph discloses Zhang et al. conducted a high-throughput screen of more than 50,000 synthetic compounds and natural compound that activated the Insulin Receptor (IR). The compound, however, turned out to not be derived from an edible plant source at all. Rather, the compound was derived from a natural fungal extract (Pseudomassaria) that had been recovered from leaves of an undetermined plant collected near Kinshasa, Democratic Republic of Congo. This work showed, however, that it was at least possible to identify a small molecule capable of having partial activity toward the Insulin Receptor (IR.)] and a natural botanical extract (an active ingredient), wherein the extract is an aqueous extract of Cichorium Endivia var. Latifolium (i.e. all the claimed active ingredients are naturally-occurring ingredients). [Please note that where the claim is to a nature-based product in combination with non-nature based elements (e.g. a claim to “a yogurt starter kit comprising Lactobacillus in a container with instructions for culturing Lactobacillus with milk to produce yogurt”), the markedly different characteristics analysis should be applied only to the nature-based product limitation (MPEP 2106.04(c)(I)(A))]. Moreover, the clamed composition (as a pharmaceutical and/or nutritional supplement) comprising the botanical extract, wherein the extract is an aqueous extract of Cichorium Endivia var. Latifolium is not markedly different from its naturally-occurring counterpart because there is no adequate indication and/or sufficient evidence/support within Applicant’s specification that the claimed natural botanical extract has any characteristics or properties that are different from the naturally-occurring counterpart (including the natural compounds found therein).- i.e., there is no adequate indication and/or sufficient evidence/support within Applicant’s specification that the instantly claimed preparatory steps (i.e. the claimed natural botanical extract obtained by the instantly claimed preparatory step of an aqueous extract of Cichorium Endivia var. Latifolium as disclosed within Applicant’s specification’s in paragraphs [0044]-[0045] has caused the resulting extract/product to have any characteristics that are different from the naturally-occurring counterpart. [Also, Please note that there is no adequate evidence/support within Applicant’s specification that its claimed composition/extract is markedly different in terms of having a change in structure of having an unexpected functional difference (i.e. a difference in properties and/or characteristics) as compared to its/their naturally-occurring counterpart(s) and/or there is no adequate evidence/support within Applicant’s specification that its claimed composition comprising the claimed natural compound (as an active ingredient) and the claimed natural botanical extract (as an active ingredient) is markedly different in terms of having a change in structure (by demonstrating “synergism”) that produced an unexpected/synergistic functional effect as compared to its/their naturally-occurring counterpart(s)] and that the composition has any characteristics or properties that are different from the naturally-occurring counterpart(s) (including the natural compounds found therein- e.g. step 2A1(MPEP 2106.04 (a-c)). Moreover, the cited claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not recite any additional elements (i.e. do not recite additional elements/steps that integrate the exception into a practical application and do not recite additional elements that amount to significant more than the exception of the claimed naturally-occurring ingredients).
Therefore, the claimed composition/extract is not deemed to be markedly different from what exists in nature in terms of structural and/or functional differences. In other words, the claims do not set forth a marked difference in terms of structural and/or or functional differences (properties and/or characteristics) as compared to the naturally-occurring counterpart(s) (see, e.g., Diamond v. Chakrabarty, 447 U.S. 303(1980)). Please note that combining natural products does not remove the claims from reading upon a judicial selection (Funk Brothers Seed Col. V. Kalo Inoclulant Col. – 333 U.S. 127 (1948)) because again there is no sufficient evidence/support of a marked difference brought about by combining the instantly claimed natural products. Please also note that modifying the concentration of the product/composition is not sufficient to remove the claimed composition from a judicial exception (see, e.g., Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. __, 133 S. Ct. 2107, 106 USPQ2d 1972 (2013)).
Thus, when the relevant factors are analyzed, they weigh against a significant difference between the claimed invention and a judicial exception. Therefore, the claimed invention is not considered to be patent eligible subject matter.
Claims 1-4, 8-9, 18 are rejected under 35 U.S.C. 102(e) as being anticipated by Chapal (WO2013072522 A1) as evidenced by Ihara et al (“Chlorogenic Acid and Caffeine in Coffie restore insulin signaling in Pancreatic Beta Cells”, Kobe J. Med Sci. Vol.69, No. 1 PPE1-E8 (2023)).
Chapal et al disclose making extracts from Cichorium endivia including using an aqueous solvent system (claims 5,6,9) and using the extracts to treat physiological conditions associated with T2DM and pre-T2DM (claims 15-19).
Specifically called out is “cholorgenic acid” which is a natural ester. (See claim 1). Ihara teaches that “Irs2 expression was significantly increased in the chlorogenic acid treated groups.”. (See Ihara E3 first full paragraph).
They also disclose that the extract can be provided as a nutraceutical or a pharmaceutical composition (claims 20 and p.7 line 4).
Given that the aqueous extract is from the same species as instantly, the anti-diabetic effects of the extract are also mediated through increasing IRS2 activity. Accordingly, claims 1-4, 8-9, 18 are rejected under 35 U.S.C. 102(e) as being anticipated by Chapal.
Due to the 112b issue above, it is unclear as to how you would apply applicant’s indefinite standard to prior art formulation. It is assumed that chlorogenic acid has the claimed insulin equivalent units as Ihara teaches the direct upregulation of IRS-2.
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 AMJAD A ABRAHAM whose telephone number is (571)270-7058. The examiner can normally be reached Mon-Friday 830 AM to 500 PM.
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AMJAD A. ABRAHAM
SPE AU 1663
Art Unit 1663
/Amjad Abraham/SPE, Art Unit 1663
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