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 .
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.
Priority
Acknowledgment is also made of applicant's claim for foreign priority under 35 U.S.C. 119(a)-(d) to Application No. 10-2023-0014510, filed on 02/02/2023 in Republic of Korea.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-6, in the reply filed on 08/31/2026 is acknowledged.
Claims 7-9 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups of invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/31/2026.
Information Disclosure Statement
The information disclosure statement (IDS) filed 01/05/2024, 07/30/2025 and 03/09/2026 are considered, initialed and are attached hereto.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 1-6 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed.
The claims are directed to a pharmaceutical composition, the composition comprising “an arginase-1 inhibitor as an active ingredient”.
At claim 1, the claims are directed a genus of active ingredient, the ingredient tied to the functional ability that is “preventing or treating ischemic cerebrovascular disease” (claim 1).
At claim 3, the claims are directed to a genus of active ingredient, the ingredient tied to the functional ability that is “preventing or treating ischemic cerebrovascular disease” (claim 1), and which achieves the “suppression of arginase-1 by way of deleting the gene encoding arginase-1 protein or inhibiting the function of arginase-1 protein” (claim 3).
At claim 5, the claims are directed to a genus of active ingredient, the ingredient tied to the functional ability that is “preventing or treating ischemic cerebrovascular disease” (claim 1) and “reduces the expression rate of inflammatory cytokines” (claim 5). The claim language broadly encompasses any “inflammatory cytokine” (describes cytokine who expression is reduced in relation to an unspecified arginase-1 inhibitor). Further, inflammatory cytokine necessarily expressed in microglia (see claim 6, “expression rate of inflammatory cytokines is measured in microglia”).
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with known or disclosed, and correlation between function and structure), (4) Method of making claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
The purpose of the written description requirement is "to ensure that the inventor had possession, as of the filing date of the application relied on, of the specific subject matter later claimed by him." In re Edwards, 568 F.2d 1349, 1351-52, 196 USPQ 465, 467 (CCPA 1978).
Regarding Applicant’s actual reduction to practice, Applicant’s originally filed specification, including Applicant’s examples, fail to recite or specify any particular “active ingredient” that is considered to be an “arginase-1 inhibitor”. There are no disclosed species of arginase-1 inhibitors in the originally filed specification. There is also no indication as to which specific arginase-1 inhibitors known in the art exhibit the claimed functional requirements.
Regarding the disclosure of drawings or structural chemical formulas or sufficient relevant identifying characteristics (such as, i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with known or disclosed, and correlation between function and structure), while arginase-1 inhibitors are known to those of ordinary skill in the art, in the instant application there is are no disclosed structural characteristics or features shared among or specific to arginase-1 inhibitors that achieve the claimed functional abilities as indicated in detail above (i.e., no disclosed shared structure/compositional feature that is specific to arginase-1 inhibitors capable of/which achieves prevention/treatment of ischemic cerebrovascular disease (claim 1), a feature common to all species which suppress arginase-1 expression by deleting the gene encoding arginase-1 protein or inhibiting the function of arginase-1 protein (claim 3), or a feature common to all species capable of/which achieves reduced expression rate of inflammatory cytokines (claim 5) in microglia (claim 6)).
Although claim 4 appears somewhat limiting in terms of product structure/composition (see is selected from “DNA, RNA, polypeptides, proteins, ligands, enzymes, antibodies, antigens, natural compounds, synthetic compounds and active molecules”), the limitations of this claim are not actually limiting as the claim encompasses nearly any type of inhibitor/molecule.
Regarding the level of skill and knowledge in the art, and the predictability in the art, see Li et al., Depletion of Arg1-Positive Microglia/Macrophages Exacerbates Cerebral Ischemic Damage by Facilitating the Inflammatory Response, Int. J. Moll. Sci, 23, (2022), (13 pages) (IDS entered 07/30/2025), regarding the expression of Arginase 1 (Arg1), it is known that the expression is altered in peripheral circulation after stroke (stroke considered a form of ischemic cerebrovascular disease), Li teach there is growing evidence that indicates that ischemic stroke induces upregulated Arg1 expression in the central nervous system, especially in activated microglia and macrophages (see Li et al. at the abstract). Importantly, it is noted that Li et al. teach that absence of Arg1+ microglia/macrophages significantly increased the production of pro-inflammatory cytokines and suppressed the expression of anti-inflammatory factors (see abstract).
Li et al. teach at page 7, that studies have shown that enhanced Arg activity and polyamine synthesis are involved in the pathogenesis of brain injury, such as Alzheimer’ Disease and Parkinson’s disease, linking to neuronal death. However, Li et al. also acknowledge that there is controversy among the prior art having to do with the role of Arginase in cerebral ischemia, teaching inhibition of systemic Arg expression by the specific inhibitors L-citruline and L-ornithine improves animal behavior and reduces infarction and edema after stroke.
Based on Li et al., it is not readily predictable what arginase-1 inhibitors are capable of/achieve the desired functional ability. For example, referring to Li above, Li supports that it is not predictable that any and all inhibition of arginase 1 results in reduced expression of inflammatory cytokines, given that depletion of arginase 1 expressing microglia/macrophages results in increase expression of some inflammatory cytokines (see page 6, para 1, depletion lead to significant increase in IL-1β and TNF-α, both considered to be “inflammatory cytokine” as claimed).
Additionally, regarding the state of the prior art and predictability, see also Barakat et al., Effectiveness of arginase inhibitors against experimentally induced stroke, Naunyn-Schmiedeberg’s Archives of Pharmacology, 391, (2018), p.603-612 (IDS entered 03/09/2026), Barakat teach inflammatory mediators (see including an inflammatory cytokine, see e.g., TNF-α) increase arginase-1 activity (see page 603, col. 2, para 2). At page 607, col. 2, para 2, Barakat teach treatment with L-citruline and L-ornithine caused reduction in TNF-α relative expression (see also page 609, col. 2, para 4).
Based on what was known in the art, while it is recognized that L-citruline and L-ornithine may be responsible for the reduction in an inflammatory cytokine (TNF-α), it is not readily predictable that these specific inhibitors would reduce all inflammatory cytokines, or even that all arginase inhibitors would reduce expression of TNF-α, as encompassed by the extremely broad claim language. Especially considering the citation of Li et al. above (which indicated a correlation with increased expression for some inflammatory cytokines).
As noted previously above, the recited claims are extremely broad in scope, the claims are not limited in terms of “arginase-1 inhibitor”, not limited to a specific “ischemic cerebrovascular disease”, or to reduction of any particular “inflammatory cytokine”, and Applicant’s originally filed specification fails to specify any particular examples of or species of “arginase-1 inhibitors” which achieve the claimed function.
Based on all the above factors discussed above considered in detail together, while arginase-1 inhibitors generally are known and available in the prior art, it is not readily predictable that Applicant was in possession of a pharmaceutical composition as claimed, namely any and all compositions comprising arginase-1 inhibitors capable of preventing or treating ischemic cerebrovascular disease (claim 1), and which reduce the expression of any and all inflammatory cytokines (claims 5 and 6).
Further, regarding the limitation “preventing… ischemic cerebrovascular disease”, none of the examples in the originally filed application demonstrate or support the ability to apply any arginase-1 inhibitor in order to “prevent” ischemic cerebrovascular disease. For example, there is no disclosure that supports the ability to prevent a subject from experiencing ischemic cerebrovascular disease.
For all of these reasons, there is insufficient written description to support that Applicant was in possession of the entire scope encompassed by the claimed composition, namely there is insufficient written description to support Applicant was in possession of the genus of arginase-1 inhibitor described in terms of the required functional limitations.
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 2, 3 and 6 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.
Claims 2 and 3 each recite the limitation "the expression of arginase-1 " in lines 1-2. There is insufficient antecedent basis for this limitation in the claims. Specifically, claim 1 is directed to a composition comprising “an arginase-1 inhibitor as an active ingredient” as the only required component of the product invention. There is no earlier reference to “expression of arginase-1” or the functional effect of the claimed composition on “expression of arginase-1”. Further because this limitation is not related to or recited in reference with the claimed composition (e.g., is not a functional limitation that is tied to the composition or ingredient) it does not clearly add additional limitation to the composition or ingredients of the composition themselves. As a result, the claim language is indefinite.
Claim 6 recites “wherein the expression rate of the inflammatory cytokines is measured in microglia”, the claimed limitation reads as a method step (“expression...measured in”), however, the claimed invention is directed to a product, and as such, does not include any method steps, such as measuring. The recited language is indefinite because it is confusing in that it reads as a method step.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 depends from claim 1, and claim 1 is directed to a composition comprising “an arginase-1 inhibitor as an active ingredient”, this limitation recited as the only required component of the product invention. There is no earlier reference to “expression of arginase-1” or the functional effect of the claimed composition on “expression of arginase-1” (see as discussed in detail above, under 35 U.S.C. 112(b)). The “wherein” clause of claim 2 fails to further limit the product invention, as it fails to recite, imply or suggest any additional component or feature specific to the claimed product.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-6 are rejected under 35 U.S.C. 101 because the claims are directed to a law of nature, specifically a nature-based product (a composition comprising an “arginase-1 inhibitor”).
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because species there are species of “arginase-1 inhibitors” that are naturally occurring and such an inhibitor as a composition does not result in markedly different characteristics as compared with those species that are naturally occurring counterpart.
For example, see the claims broadly recite “an arginase-1 inhibitor”, the claims are not limited to any particular species of inhibitor. Some known arginase-1 inhibitors are, for example, those as taught by Barakat et al., Effectiveness of arginase inhibitors against experimentally induced stroke, Naunyn-Schmiedeberg’s Arch. Pharmacol., 391, (2018), p. 603-612, namely L-citruline and L-ornithine. These are arginase-1 inhibitors that would be encompassed by the recited claim language.
See Shilpa N. Kaore, Navinchandra M. Kaore, Chapter 53 - Citrulline: Pharmacological perspectives and role as a biomarker in diseases and toxicities, Editor(s): Ramesh C. Gupta, Biomarkers in Toxicology, Academic Press, 2014, Pages 883-905. L-citrulline (Cit) is a naturally occurring nonessential amino acid, present in mammals and also in every living organism (chapter abstract).
See also Fukuda, T., Haraguchi, A., Kuwahara, M. et al. l-Ornithine affects peripheral clock gene expression in mice. Sci Rep 6, 34665 (2016). https://doi.org/10.1038/srep34665. Fukuda et al. at page 1, para 3 teach L-ornithine is a naturally occurring type of non-protein amino acid found in foods such as corbicula, cheese and flounder, it is generated during the urea cycle in the liver and kidney.
These are two examples that support the breadth of the claimed “arginase-1 inhibitor” genus encompasses species that are natural products, as each of these examples are not markedly different from nature (i.e., are products of nature themselves). Although they may not be naturally occurring as part of a composition (when the composition is limited to or inclusive of additional components), there is further no evidence that simply providing these species as active agents in a composition changes the biological or pharmacological functions or activities. There is no indication in the claims or originally filed specification that the claimed composition has any characteristics (structural, functional or otherwise) that are different from how these species exist in nature as natural products. As a result, the claimed subject matter is ineligible under 35 U.S.C. 101 because the claimed reagent is a nature-based product not markedly different
Dependent claims fail to further limit or introduce additional structure such that would result in a markedly distinct species that is different from how it exists naturally.
For all of these reasons, the claimed reagent is ineligible subject matter.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Barakat et al., Effectiveness of arginase inhibitors against experimentally induced stroke, Naunyn-Schmiedeberg’s Arch. Pharmacol., 391, (2018), p. 603-612.
Barakat et al. investigated the effect of arginase inhibitors (namely the species L-citruline and L-ornithine) against induced ischemic stroke (abstract), and their results lead them to suggest the use of arginase inhibitors as a therapeutic to treat stroke (abstract). See page 609, the inhibitors of Barakat reduce the expression of arginase I and II. Further see at page 609, col. 1, para 6, L-citruline was shown previously in the art (acknowledged by Barakat) as exerting cerebrovascular protective effect associated with restoration of the reduced hippocampal expression of eNOS in BCCAO ischemia model. See also page 609, conclusions at the end of col. 2.
Barakat et al. anticipates the claimed invention at claim 1 because Barakat et al. is teaching a composition comprising an arginase-1 inhibitor (orally administered L-citruline and L-orinthine, which inhibit expression of Arginase I and II), and teaches these inhibitors achieve treatment of ischemic cerebrovascular disease (i.e., stroke).
Claim 2 recites “wherein the expression of arginase-1 is expressed within infiltrating macrophages”, see as discussed in detail above, the claim fails to recite or imply any additional structural/compositional feature to the claimed compositions or ingredients recited at claim 1. At most, the recited limitation could at best be directed to the intended use of the claimed composition, in inhibiting arginase-1 expression in infiltrating macrophages, when applied as a composition for treatment (i.e., when applied for its intended use).
Claim 3 recites “wherein the expression of arginase-1 is suppressed by deleting a gene encoding arginase-1 protein or inhibiting the function of arginase-1 protein”. As cited above, Barakat teach a composition that inhibits expression of arginase-1, and inhibiting expression (reducing expression), in turn is considered to inhibit function (as there is less protein expressed, thereby effecting function).
Claim 4, Barakat teaches treatment with L-citruline and L-ornithine, each of which reads on “bioactive molecules”.
Regarding claims 5 and 6, see Barakat teach inflammatory mediators (see including an inflammatory cytokine, see e.g., TNF-α) increase arginase-1 activity (see page 603, col. 2, para 2). At page 607, col. 2, para 2, Barakat teach treatment with L-citruline and L-ornithine caused reduction in TNF-α relative expression (see also page 609, col. 2, para 4).
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at 571-272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ELLEN J MARCSISIN/ Primary Examiner, Art Unit 1677
Prosecution Insights