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 .
DETAILED ACTION
Continued Examination under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission of RCE on November 24, 2025 and amendment after final filed on November 24, 2025 has been entered. Applicants canceled all previous pending claims (claims 1-32) and presented new claims 33-37.
The restriction requirement was deemed proper and made FINAL previously. The presently pending claims are directed solely to the election invention; therefore, examination is directed to that invention. The election of species requirement is withdrawn. Claims 33-37 are examined on the merits of this office action.
Withdrawn Rejections
The rejection of claim(s) 15, 20 and 25 under 35 U.S.C. 103 as being unpatentable over Chun (WO2002009741 A1, cited previously) as evidenced by NIH (see attached handout, accessed on 10/4/2024) in view of Wong (WO2014138319 A2, cited previously) is withdrawn in view of amendment of the claims filed November 24, 2025.
*Please note that because applicant canceled claims 1–32 and presented new claims 33-37 following the RCE, the nonstatutory double patenting rejection is maintained but revised to address the newly presented claims (see Below). Although the claim numbering and wording have changed, the newly added claims are not patentably distinct from the claims of the reference application/patent previously cited for the double patenting rejection. The newly presented claims recite subject matter that is the same as or an obvious variation of the subject matter previously rejected for double patenting. Accordingly, the double patenting rejection is continued and updated to correspond to the current claim set.
Maintained/Revised Rejection
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 33-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9, 11-12, 14-15, 17-18, 20, 22-26 of copending Application No. 17247153 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of reducing serum arginine, reducing body weight, lowering blood glucose, increasing insulin sensitivity, reducing insulin resistance, reducing glucose intolerance, reducing lipid accumulation, preventing fat mass gain, reducing fat mass, reducing lipogenesis, increasing thermogenesis, increasing fatty acid oxidation, reducing plasma insulin, reducing plasma leptin and reducing plasma cholesterol comprising:administering a therapeutically effective amount of an arginine depleting agent to a subject with overweight, obesity, prediabetes mellitus, type 1 diabetes mellitus, type 2 diabetes mellitus, hepatic steatosis, renal steatosis, pancreatic steatosis, cardiac steaotosis, myosteatosis, steatohepatitis, hyperglycemia, hypertriglyceridemia, dyslipidemia, hyperinsulinemia, hyperleptinemia or hypercholesterolemia, the arginine depleting agent being an arginine catabolic enzyme selected from the group consisting of an arginase protein selected from the group consisting of Homo sapiens (human) arginase I, Homo sapiens (human) arginase II, Bacillus caldovelox arginase, Thermus thermophilus arginase, and Sus scrofa arginase I, an arginine deiminase protein selected from the group consisting of Mycoplasma hominis arginine deiminase, Mycoplasma arginini arginine deiminase, and Mycoplasma arthritidis arginine deiminase, and an arginine decarboxylase protein selected from the group consisting of Escherichia coli arginine decarboxylase, Homo sapiens (human) arginine decarboxylase polypeptide, and Thermus thermophilus arginine decarboxylase; or the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO: 104;wherein administration of the arginine depleting agent depleting serum arginine in the subject maintains an arginine concentration in the subject's serum below 50 pM (claim 33). The instant application further claims wherein the arginase protein, arginine deiminase protein, or arginine decarboxylase protein further comprises an albumin binding domain or human serum albumin, or a human IgG Fc domain (claim 34); wherein the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO:101, SEQ ID NO: 102, SEQ ID NO: 103, or SEQ ID NO: 104 (claims 35); wherein the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, or SEQ ID NO: 104, wherein SEQ ID NO: 101, SEQ ID NO:102, SEQ ID NO: 103, and SEQ ID NO: 104 further comprise one or more polyethylene glycol (PEG) groups (claim 36); wherein the arginine catabolic enzyme consists of SEQ ID NO: 49, SEQ ID NO: 50, or SEQ ID NO: 101 with one or more polyethylene glycol (PEG) groups (claim 37).
Co-pending Application 17/247153 claims “A treatment of at least one health condition in a subject in need thereof, wherein the at least one health condition is selected from the group consisting of prediabetes mellitus, type 2 diabetes, obesity, a metabolic disorder selected from glucose intolerance and insulin resistance and related complications selected from the group consisting of steatosis and whitening of brown fat, wherein the metabolic disorder and the related complications are associated with one or more of obesity, prediabetes mellitus, and type 2 diabetes, the method comprising the step of co- administering a therapeutically effective amount of an arginine depleting agent and a therapeutically effective amount of a second therapeutic agent to the subject, wherein the arginine depleting agent comprises an arginine catabolic enzyme selected from the group consisting of an arginase protein selected from the group consisting of Homo sapiens (human) arginase I, Homo sapiens (human) arginase II, Bacillus caldovelox arginase, Thermus thermophilus arginase, and Sus scrofa arginase I, an arginine deiminase protein selected from the group consisting of Mycoplasma hominis arginine deiminase Mycoplasma arginine arginine deiminase, and Mycoplasma arthritis arginine deiminase and an arginine decarboxylase protein selected from the group consisting of Escherichia coli arginine decarboxylase, Homo sapiens (human) arginine decarboxylase polypeptide, and Thermus thermophilus arginine decarboxylase; or the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO:103, SEQ ID NO: 104 or SEQ ID NO: 107; and the second therapeutic agent is selected from the group consisting of an autophagy inducing agent, a glucose lowering agent, a retinoid derivative, an (-)-epigallocatechin-3-gallate (EGCG) derivative, and a rapamycin derivative” (claim 1). The co-pending application further claims arginine level below 50 uM (claim 3); fusion to an ABD or FC (Claim 7); SEQ ID Nos:49-50, 101-102, 104 with PEG (claims 23-24).
The sequences of the co-pending application are identical to the instant claims SEQ ID Nos: including Arginase I peptides with ABD.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
New Objection
Claim 33 is objected to for the following informality: the limitation “..to a subject with overweight, obesity…” is grammatically incorrect. Appropriate terminology would be “subject who is overweight” or “overweight subject”.
Claim 33 is further objected to for the following informality: the wherein clause at the end of claim 33 should be amended as follows “wherein administration of the arginine depleting agent maintains the subject’s serum arginine concentration below 50 uM-.
Claim 34 is objected to for the following informality: the limitation of “…further comprises an albumin binding domain or human serum albumin, or a human IgG Fc domain” should be amended as follows -further comprises an albumin binding domain, human serum albumin or an IgG Fc domain-.
New Rejections
35 USC § 112, first paragraph
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 33-37 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 reducing serum arginine, reducing body weight, lowering blood glucose, increasing insulin sensitivity, reducing insulin resistance, reducing glucose intolerance, reducing lipid accumulation, preventing fat mass gain, reducing fat mass, reducing lipogenesis, increasing thermogenesis, increasing fatty acid oxidation, reducing plasma insulin, reducing plasma leptin and reducing plasma cholesterol in specific patient populations (high fat diet, obesity, type 2 diabetes) with Arginase I, does not provide enablement for having those effects in any patient population lised in claim 33 (such as type 1 diabetes) with any arginine depleting agent as claimed (which is inclusive to many arginase proteins, arginine deiminase proteins, arginine decarboxylase and fusions thereof). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
*Please note that all references were cited and provided previously.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to “A method of reducing serum arginine, reducing body weight, lowering blood glucose, increasing insulin sensitivity, reducing insulin resistance, reducing glucose intolerance, reducing lipid accumulation, preventing fat mass gain, reducing fat mass, reducing lipogenesis, increasing thermogenesis, increasing fatty acid oxidation, reducing plasma insulin, reducing plasma leptin and reducing plasma cholesterol comprising:administering a therapeutically effective amount of an arginine depleting agent to a subject with overweight, obesity, prediabetes mellitus, type 1 diabetes mellitus, type 2 diabetes mellitus, hepatic steatosis, renal steatosis, pancreatic steatosis, cardiac steaotosis, myosteatosis, steatohepatitis, hyperglycemia, hypertriglyceridemia, dyslipidemia, hyperinsulinemia, hyperleptinemia or hypercholesterolemia, the arginine depleting agent being an arginine catabolic enzyme selected from the group consisting of an arginase protein selected from the group consisting of Homo sapiens (human) arginase I, Homo sapiens (human) arginase II, Bacillus caldovelox arginase, Thermus thermophilus arginase, and Sus scrofa arginase I, an arginine deiminase protein selected from the group consisting of Mycoplasma hominis arginine deiminase, Mycoplasma arginini arginine deiminase, and Mycoplasma arthritidis arginine deiminase, and an arginine decarboxylase protein selected from the group consisting of Escherichia coli arginine decarboxylase, Homo sapiens (human) arginine decarboxylase polypeptide, and Thermus thermophilus arginine decarboxylase; or the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO: 104;wherein administration of the arginine depleting agent depleting serum arginine in the subject maintains an arginine concentration in the subject's serum below 50 pM.”
The claims encompass multiple distinct arginine catabolic enzyme classes (argI, ArgII, arginine deiminase, and arginine decarboxylase), including homologous variants and methods of treating numerous metabolic and steatotic diseases and conditions and endpoints. This represents a broad functional genus spanning multiple enzyme types and therapeutic applications. The invention concerns therapeutic metabolic modulation through enzymatic depletion of arginine, a central metabolic and signaling substrate. In addition, each enzyme has varying effects and different signaling pathways.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The relevant art involves advanced biochemical, metabolic, and therapeutic enzyme technologies. While a person of ordinary skill would be highly trained, such skill would not eliminate the need for substantial experimental investigation across different enzyme classes and disease contexts in an unpredictable field.
There is unpredictability in the art regarding reduced arginine levels with obesity/diabetes and the lack of arginine contributing to disease severity as evidenced by Pernow (Cardiovascular Research (2013) 98, 334–343, cited previously). Pernow teaches that “Available data clearly suggest that increased activity of arginase is of importance for several pathological changes associated with cardiovascular diseases. The effects seem to be exerted mainly via interference with NO bioavailability by limiting L-arginine sources and contributing to oxidative stress. Arginase therefore presents an attractive and promising pharmacological target in order to reverse the ‘arginine steal phenomenon’, enhance NO production, and limit oxidative stress (Figure 2). These effects of arginase inhibition have great potential against several cardiovascular diseases described in the present review” (see conclusion).
Ijaz (Microvascular Research 70 (2005) 129 – 136, cited previously) teaches “l-Arginine improved hepatic arterial and portal blood flows as well as microcirculation in fatty livers ( P < 0.05), while l-NAME significantly worsened these parameters” (see abstract, results). Ijaz teaches is involved in the modulation of hepatic microcirculatory perfusion and oxygenation in cholesterol-induced hepatic steatosis. NO metabolisms may be regulated as a potential therapeutic strategy for impaired microcirculation in hepatic steatosis (see conclusion). Thus, depleting NO via arginase would be detrimental. Furthermore Moon (PLoS ONE 9(7): e103048, cited previously) teaches that “Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function” (see conclusion, abstract).
Beleznai (Am J Physiol Heart Circ Physiol 300: H777–H783, 2011, cited previously) teaches that Arginase I contributes to diminished coronary arteriolar dilation in patients with diabetes (see abstract).
Johnson (Obesity / Volume 23, Issue 2 / p. 383-390, 2015, cited previously) teaches that Arginase activity and expression was increased while global arginine bioavailability decreased in obese ZRs (see “Results” in abstract). Johnson teaches that administration of arginine or arginase inhibitors lowered blood pressure in obese but not lean animals, and this was associated with an improvement in systemic arginine bioavailability (see Results, last three lines). Johnson concludes that “Arginase promotes endothelial dysfunction and hypertension in obesity by reducing arginine bioavailability. Therapeutic approaches targeting arginase represent a promising approach in treating obesity-related vascular disease” (See conclusion).
The art is unpredictable with respect to therapeutic outcomes resulting from modulation of arginine metabolism. The prior art indicates that increasing or decreasing arginine pathway activity may produce opposite effects depending on enzyme type, isoform, and physiological context. Additionally, the claimed enzymes operate through different biochemical mechanisms and produce different metabolites, further reducing the predictability across the full claimed genus.
(5) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
Applicants reduce to practice the following: Example 1 uses instant SEQ ID NO:50 (human Arginase, with ABD peptide) and applicants state treatment once a week can induce a 7 day intermittent fasting cycle composed of fasting and refeeding period. Applicants further state diet induced obese mice were treated with SEQ ID NO:50 and that these mice exhibited repeat cycles of intermittent fasting throughout treatment period (reduced food intake). Example 4 shows that SEQ ID NO:50 improves insulin resistance and impaired glucose tolerance with HFD; Example 7 shows improvement of cognitive defects found in HFD mice; Example 14 shows lifespan was increased in ordinary mice; Example 15 shows induced of autophagy in HFD mice. Taken together, the Examples showed treatment high fat diet mice and diet induced obese mice and the effects of SEQ ID NO:50 on the ability to cause fasting (reduced food intake) and the protective effects thereof (insulin resistance, glucose utilization). Applicants also utilize arginine Deiminase (SEQ ID NO:107 ADI fused to ABD). Applicant’s specification states “57BL/6J male mouse with pre-existing obesity induced by a HFD was administered via i.p. injection with 5 U ADI-ABD (SEQ ID NO: 107). Food intake decreased to a minimum level after the first day and then gradually increased to the normal level FIG. 23A). The trend of fasting followed by refeeding is similar but not identical to that of N-ABD094-rhArg (SEQ ID NO: 50), which has minimum levels of food intake at about Day 2 to Day 3 instead of Day 1. For the body weight, in the first cycle, it decreased from 47 g to about 44 g in 2 days and maintained at this level during refeeding phase (FIG. 23B) [0233]
The specification does not provide comparable working examples, dosing guidance, or disease model data for Arg II or arginine decarboxylase embodiments within the claimed methods.
(8) The quantity of experimentation necessary:
Given the breadth of enzyme classes and disease indications claimed, the mechanistic differences among the enzymes, and the unpredictability in the art, substantial experimentation would be required to determine which additional enzymes, variants, doses, and treatment contexts would achieve the claimed therapeutic results. Such experimentation is undue.
In view of the Wands factors, the specification does not enable a person of ordinary skill in the art to make and use the claimed invention commensurate in scope with the claims without undue experimentation. Although certain arginine-depleting agents have been reduced to practice, the disclosure does not reasonably enable the broad range of arginine-depleting agents, structural variants, fusion constructs, and therapeutic applications recited in the claims.
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.
Claim(s) 33-36 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Debosch (WO2020009740A2, priority date of 4/25/20218).
Debosch teaches “A method for treating a metabolic disease or related disorder in a subject in need thereof comprising administering to the subject a composition comprising a therapeutically effective amount of an arginine deprivation agent” (see claim 1). Debosch teaches treatment of obesity and diabetes mellitus (see abstract, paragraph 0003). Regarding claim 33, Debosch teaches wherein the arginine deprivation agent is one or more of an arginase, an arginine deiminase or an arginine decarboxylase (see claim 2) and is Arginase I (see claim 11, SEQ ID NO:1 is human arginase I, also claims 1, 9-11). In particular, Debosch teaches use of human ArgI and II (see paragraph 0042).
Regarding claim 33, Debosch teaches the same method of the instant claims including administering the same agent (human arginase I) for the same purpose (reducing arginine and treating obesity) and thus the concentration in the subjects serum will be maintained below the levels listed in instant claim 33 given the inherent properties of the arginine depleting compound.
Regarding claim 34, Debosch teaches linking the arginine degrading enzyme to Fc or albumin from human serum (see claim 14, also paragraph 0061). Regarding claims 33, 35, 36, Debosch teaches wherein the arginine deprivation agent is Arginase I (see claim 11, SEQ ID NO:1 is human arginase I which is identical to instant SEQ ID NO:103, also claims 1, 9-11). Regarding claim 36, Debosch additionally teaches one or more PEG groups (see claim 15).
Regarding claim 33, “reducing serum arginine, reducing bodyweight, lowering blood glucose, increasing insulin sensitivity, reducing insulin resistance, reducing glucose intolerance, reducing lipid accumulation….reducing plasma insulin, reducing plasma leptin and reducing plasma cholesterol…”, in the instant case, Debosch discloses administering the same arginine depleting agent of the instant claims to the same subject population (patients with diabetes and obesity) and thus would inherently result the above result oriented effects. The effects stated in the preamble are inherent to administering the compound with the same purpose of depleting arginine in the same patient population (diabetes and obesity). Additionally, Debosch specifically teaches “effective amount is an amount capable of improving energy homeostasis, decreasing fat mass, or increasing lean mass in a subject in need thereof. In some embodiments, an effective amount is an amount capable of improving weight loss, improving fat composition, preventing fasting hypothermia or increasing insulin sensitivity subject in need thereof. In some embodiments, an effective amount is an amount capable of protecting against hepatic and peripheral fat accumulation, protecting against hepatic inflammatory responses, or improving glucose intolerance in a subject in need thereof” (See paragraph 00131).
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) 33-37 are rejected under 35 U.S.C. 103 as being unpatentable over Debosch (WO2020009740A2, priority date of 4/25/20218) in view of Wong (US20140255377 A1, cited previously).
Debosch teaches “A method for treating a metabolic disease or related disorder in a subject in need thereof comprising administering to the subject a composition comprising a therapeutically effective amount of an arginine deprivation agent” (see claim 1). Debosch teaches treatment of obesity and diabetes mellitus (see abstract, paragraph 0003). Regarding claim 33, Debosch teaches wherein the arginine deprivation agent is one or more of an arginase, an arginine deiminase or an arginine decarboxylase (see claim 2) and is Arginase I (see claim 11, SEQ ID NO:1 is human arginase I, also claims 1, 9-11). In particular, Debosch teaches use of human ArgI and II (see paragraph 0042).
Regarding claim 33, Debosch teaches the same method of the instant claims including administering the same agent (human arginase I) for the same purpose (reducing arginine and treating obesity) and thus the concentration in the subjects serum will be maintained below the levels listed in instant claim 33 given the inherent properties of the arginine depleting compound.
Regarding claim 34, Debosch teaches linking the arginine degrading enzyme to Fc or albumin from human serum (see claim 14, also paragraph 0061). Regarding claims 33, 35, 36, Debosch teaches wherein the arginine deprivation agent is Arginase I (see claim 11, SEQ ID NO:1 is human arginase I which is identical to instant SEQ ID NO:103, also claims 1, 9-11). Regarding claim 36, Debosch additionally teaches one or more PEG groups (see claim 15).
Regarding claim 33, “reducing serum arginine, reducing bodyweight, lowering blood glucose, increasing insulin sensitivity, reducing insulin resistance, reducing glucose intolerance, reducing lipid accumulation….reducing plasma insulin, reducing plasma leptin and reducing plasma cholesterol…”, in the instant case, Debosch discloses administering the same arginine depleting agent of the instant claims to the same subject population (patients with diabetes and obesity) and thus would inherently result the above result oriented effects. The effects stated in the preamble are inherent to administering the compound with the same purpose of depleting arginine in the same patient population (diabetes and obesity). Additionally, Debosch specifically teaches “effective amount is an amount capable of improving energy homeostasis, decreasing fat mass, or increasing lean mass in a subject in need thereof. In some embodiments, an effective amount is an amount capable of improving weight loss, improving fat composition, preventing fasting hypothermia or increasing insulin sensitivity subject in need thereof. In some embodiments, an effective amount is an amount capable of protecting against hepatic and peripheral fat accumulation, protecting against hepatic inflammatory responses, or improving glucose intolerance in a subject in need thereof” (See paragraph 00131).
Debosch is silent to wherein the arginine depleting enzyme (arginase I or arginine deiminase) is fused to an Albumin binding domain.
However, Wong discloses a method of treating arginine-dependent diseases (see claim 17) comprising administering a therapeutically effective amount of an arginine depleting agent fused to albumin binding domain (see claims 15 and 1). Wong teaches wherein the arginine level is below 50 µm (see figure 11). Wong teaches wherein the arginine depleting agents is an arginine catabolic enzyme and in particular, an arginine deiminase protein (see claim 1). Wong teaches fusing an albumin binding domain to the arginine depleting agent to create high activity and prolonged half life (see abstract).
It would have been obvious before the effective filing date of the claimed invention to fuse the arginine depleting enzyme of Debosch (which is inclusive to human arginase I and arginine deiminase). One of ordinary skill in the art would have been motivated to do so improve half life and activity (arginine depletion) of the agent in patients. There is a reasonable expectation of success given that Wong teaches fusion with ABD and that it is effective in depleting arginine with a prolonged half life.
Regarding claim 37, instant SEQ ID NO:49 is an ABD linked to human arginase I with a 6XHis tag. Debosch in view of Wong teach instant SEQ ID NO:49 given that SEQ ID NO:40 of Wong teaches the same 6XHis Tag, linker, ABD and Poly-N (see Figure 3, SEQ ID NO:40). Debosch teaches the human arginase I peptide found in instant SEQ ID NO:49 (see SEQ ID NO:1). Thus, the combined teachings of Debosch in view of Wong teach instant SEQ ID NO:49. Furthermore, Debosch teaches that the arginine depleting agent can comprise one or more PEG groups (see claim 15).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654