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
The amendment after non-final office action filed August 13, 2025 is acknowledged. Claims 2, 10, 13, 16, 19, 21 were cancelled, claims 1, 25-26 were amended and claims 1, 3-9, 11-12, 14-15, 17-18, 20, 22-26 are pending.
*After further review, a new rejection under obvious type Double patenting is presented blow and thus, a second Non-final follows.
Election/Restrictions
The restriction requirement was deemed proper and made FINAL previously. After further review claims 5-6, 11-12, 14-15 are rejoined. Claim 20 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1, 3-9, 11-12, 14-15, 17-18, 22-26 are examined on the merits of this office action.
*Please note the amendment to the specification filed August 13, 2025 is entered.
Withdrawn Objections/Rejections
1. The rejection of claims 1, 3-4, 7-8, 26 under 35 U.S.C. 102(a)(1) as being anticipated by Wong (US20140255377 A1, cited previously) as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18, cited previously) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
2. The rejection of claim(s) 1, 3-4 and 26 under 35 U.S.C. 102(a)(1) as being anticipated by Cheng (US20050244398 A1, cited previously) as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18, cited previously) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
2. The rejection of claim(s) 1, 3-4, 7-9, 22-24 and 26 under 35 U.S.C. 103 as being unpatentable over Wong (US20140255377 A1, cited previously) as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18, cited previously) in view of Cheng (US20050244398 A1, cited previously) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
4. The rejection of Claim(s) 1, 3-4, 7-8, 17-18, 25-26 under 35 U.S.C. 103 as being unpatentable over Wong (US20140255377 A1, cited previously) as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18, cited previously) in view of Chen (BioMedicine, December 2014, Vol. 4, No. 4, Article 1, Pages 1-6, cited previously) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
5. The rejection of claims 1, 3-4, 7-9, 17-18, 22-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9803185 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18) in view of Cheng (US20050244398 A1, cited previously) and Chen (BioMedicine, December 2014, Vol. 4, No. 4, Article 1, Pages 1-6, cited previously) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
6. The rejection of claims 1, 3-4, 7-9, 17-18, 22-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. RE48805E1 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18, cited previously) in view of Cheng (US20050244398 A1, cited previously) and Chen (BioMedicine, December 2014, Vol. 4, No. 4, Article 1, Pages 1-6, cited previously) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
7. The rejection of claims 1, 3-4, 17-18, 22-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11751050 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18) in view of Chen (BioMedicine, December 2014, Vol. 4, No. 4, Article 1, Pages 1-6) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
8. The rejection of claims 1, 3-4, 17-18, 22-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 7951366 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18) in view of Chen (BioMedicine, December 2014, Vol. 4, No. 4, Article 1, Pages 1-6) is withdrawn in view of amendment of the claims and the specification filed August 13, 2025.
9. The rejection of claim 25 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 is withdrawn in view of amendment of the claims filed August 13, 2025.
Maintained/Revised Rejections
Claim 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 1, 3-9, 11-12, 14-15, 17-18, 22-26 are/remain 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 treatment of high fat induced obesity in mice and reduction of white adipocytes hyperproliferation with a specific human arginase conjugated to ABD does not reasonably provide enablement for treating prediabetes, type 2 diabetes, a metabolic disorder and related complications (which is steatosis, whitening of brown fat, glucose intolerance and insulin resistance), 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.
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 inducing intermittent fasting, modulating autophagy, or inducing intermittent fasting and modulating autophagy resulting treatment of at least one health condition selected from the group consisting prediabetes mellitus, type 2 diabetes, obesity a metabolic disorder or related complication (i.e. insulin resistance, glucose intolerance, steatosis and whitening of brown fat which are not required to be in patients with obesity, diabetes or prediabetes), the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 Mvcoplasma hominis arginine deiminase. Mvcoplasma arginini arginine deiminase, and Mvcoplasma 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 Thernus thernophilus 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; the arginine depleting agent is co-administered with a therapeutically effective amount of a second therapeutic agent 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.”
The claims are broad with regards to the compound to be administered, and the peptides that deplete arginine and the conditions listed above. The scope encompasses multiple distinct enzyme classes, different species of enzymes, peptides having 99% sequence identity to the numerous SEQ ID Nos, and treatment of multiple metabolic disorders/complications. The scope substantially exceeds the limited number of enzyme constructs and disease models demonstrated.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
Although a person of ordinary skill would be familiar with protein therapeutics and metabolic biology, such a skill would not obviate the need for extensive experimentation to determine which specific arginine depleting agents will induce intermittent fasting and achieve the claimed therapeutic effects.
This is especially in light of 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). There is a vast number of prior art that discuss the negative impact of arginase in the metabolic disorders listed in the specification.
For example, 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) 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).
Thus, clearly there is unpredictability with regards to using arginase/arginine depleting agents for treatment of the metabolic disorders such as diabetes etc…Furthermore, this is further complicated by the fact that human arginase is actually quite toxic and is often used in treatment of cancer (see Mauldin, Translational Oncology (2012) 5, 26–31, cited previously). Thus, one might expect that higher doses of arginase could actually make the animals quite sick and affect the ability of the animal to actually consume food which would result in weight loss.
(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]
However, there is insufficient disclosure to reasonably predict (in light of the contradictory prior art) that the arginine depleting agents of the instant claims (especially in light of the prior art showing unpredictability with regards to arginine levels, arginine depleting agents and obesity and the other metabolic disorders) would be capable of treating any of the of the disorders encompassed by instant claim 1 with any of the agents found in instant claim 1.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the varying pathological manifestations and numerous factors that may contribute to development of metabolic disorders/related complications, and the high unpredictability in the art as evidenced therein (i.e. the numerous prior art references showing detrimental effects of arginase and arginine depletion in a number of said disorders), and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
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.
Response to Applicant’s Arguments
Applicants argue that claim 1 was amended to remove Alzheimer’s disease, Parkinson’s and cognitive decline. Applicants argue that the claim does not encompass treatment of any subject and the specification has been amended in a way that treatment does not encompass prevention. Applicants disagree that that Ijaz and Johnson teach unpredictability but rather teach safety and tolerance of arginine depleting treatment. As presented in the Shum Declaration, mice fed with a low-fat diet or high-fat diet and received once weekly injection of N-ABD094-rhArg (SEQ ID NO: 50) for 8 months, showed comparable health indicators, including common biomarkers of liver damage (plasma ALT, AST) and kidney function (serum creatinine, urine albumin/creatine ratio), blood pressure, heart rate, insulin sensitivity, glucose tolerance and fasting blood glucose, with age-matched lean mice. In addition, the liver, which is an organ very sensitive to toxic substances, showed no sign of toxicity (Example I, Supplementary Figure 3); and bodyweight remained constant after the initial period of reduction in bodyweight (Example I, Supplementary Figure 1B). All of which indicate that arginine depletion treatment is well tolerated and does not result in significantly toxicity as noted in point 6 of the declaration. The indications for which the Examiner has acknowledged enablement ignore the results showing high therapeutic efficacy stemming from use of arginine depleting agents both alone and in combination with the recited second therapeutic agents in the treatment of: inducing intermittent fasting (Examples 1, 3, 5, 6, 10, 12, 13, 15, 16, 18 and 21), obesity (Examples 18, 19, 21, and 22), prediabetes mellitus/type 2 diabetes (Examples 19 and 22), insulin resistance/glucose intolerance (examples 19/22), steatosis (Examples 19-20, 22-23); whitening of brown fat (Examples 19/22). The Examiner acknowledges enablement of HFD but does not extend results to obesity. With respect to the various mouse models for obesity, it is demonstrated in the Shum Declaration that arginine depletion can be used to treat obesity in genetically diabetic db/db (Exhibit A, Example IV) mice as well as aged (obese) mice fed an ordinary chow diet (Exhibit A, Example V). At Point 8. of the Shum Declaration, Professor Shum states that considering the efficacy of arginine depleting agents in the treatment of obesity in the 1) diet-induced obesity mouse model presented in the Specification together with the 2) diabetic db/db mouse model and 3) age-related obesity mouse model data in the Shum Declaration, she concludes that arginine depletion can be used to treat most, if not all, types of obesity. Accordingly, a person of ordinary skill in the art would reasonably conclude that the results of arginine depletion in HFD mice can reasonably be extended to obesity resulting from other diseases and/or health conditions. The Examiner acknowledges enablement for the use of the specific arginine depleting SEQ ID NO: 50, but does not extend these results to the use to the other arginine depleting agents recited by amended claim 1. Co-owned US Patent Application No. 16/427,593 (Hereinafter, the '593 Application), which is incorporated by reference in its entirety by the instant application, demonstrates that N-ABD094-rhArg (SEQ ID NO: 50), N-ABD094-rhArg-Co2+ [SEQ ID NO: 50 (cobalt substituted)], PEGylated His-rhArg (SEQ ID NO: 101), and arginine catabolic enzyme comprising albumin binding domain (ABD) polypeptide and an arginine deiminase polypeptide ("ABD-ADI", Shum Declaration, Example II and III) can be used as arginine depleting agents in the claimed method. Moreover, the '593 Application shows that bovine arginase, native arginine deiminase (ADI), or arginine-free medium inhibited the differentiation of mouse 3T3-L1 preadipocytes into adipocytes ('593 Application, Paragraph [0067] in Specification as filed and Figure 23) similar to N-ABD094-rhArg (SEQ ID NO: 50) (rhArg) ('593 Application, Paragraphs [0068]-[0069] in the Specification as filed and Figures 24 and 25). Given that differentiation of mouse 3T3-L1 preadipocytes into adipocytes was inhibited by both an arginine-free medium and the tested arginine depleting agents, Professor Shum concludes at Point 7. of the Shum Declaration that given the results above and the structural diversity of the tested arginine depleting agents, that any agent capable of depleting plasma arginine levels could be used in the claimed method. This conclusion is further supported by the fact that addition of arginase metabolic product L-ornithine or urea, or ADI metabolic product L-citrulline to the culture medium did not have inhibitory effects on adipogenesis and lipogenesis (See, e.g., '593 Application, Paragraph [0067] in the Specification as filed). A person of ordinary skill in the art taking the data from the working embodiments as a whole and particularly in view of the data from arginine-free medium examples ('593 Application, Paragraph [0067] in Specification as filed and Figure 23), at the time of the filing of the instant application together with the data presented in the Shum Declaration, would reasonably The quantity of experimentation needed to be performed by one skilled in the art is only one factor involved in determining whether "undue experimentation" is required to make and use the invention. Applicants respectfully submit that the Application provides sufficient guidance to enable any person skilled in the art to which it pertains, to make and/or use the invention commensurate in scope with amended claim 1 and reconsideration is respectfully requested. Claims 3, 4, 7-9, 17, 18, and 22-25 are consequently also enabled by virtue of dependency on amended claim 1. With respect to claim 26, Applicants provide the same arguments and conclude that Applicants are enabled for treating any patient in need of inducing of intermittent fasting.
Applicant’s arguments have been fully considered but not found persuasive. Applicants argue that claim 1 was amended to remove Alzheimer’s disease, Parkinson’s disease, and cognitive decline, and that the claims no longer encompass prevention. However, even as amended, the claims continue to recite broad therapeutic treatment of metabolic disorders and related complications, including obesity, prediabetes, type 2 diabetes, insulin resistance, glucose intolerance, steatosis, and whitening of brown fat, using any arginine-depleting agent as defined in the claims.
The enablement rejection was not premised solely on inclusion of neurological indications or prevention, but rather on the breadth of the claimed genus of agents and therapeutic uses relative to the limited number of embodiments actually enabled. Accordingly, removal of certain indications does not render the disclosure enabling commensurate with the full scope of the claims.
Applicants rely heavily on arguments that cited references and the Shum Declaration demonstrate safety and tolerability of arginine-depleting treatments. However, safety and tolerability are not the same as enablement of therapeutic efficacy across the claimed scope.
The enablement requirement concerns whether a person of ordinary skill in the art can make and use the claimed invention to achieve the claimed results without undue experimentation. Evidence that a specific arginine-depleting construct is tolerated in mice does not establish that all claimed arginine-depleting agents, will induce intermittent fasting and treat the full range of recited metabolic disorders.
Thus, safety data do not cure the enablement deficiencies identified. Examples and the Shum Declaration (previously filed) do not enable the full genus. Applicants argue that numerous examples, together with the Shum Declaration, demonstrate high therapeutic efficacy across obesity, prediabetes, insulin resistance, steatosis, and whitening of brown fat, and that results obtained in HFD mouse models can be extrapolated broadly. The Examiner acknowledges that the specification and declaration provide working examples (actual reduction to practice) for specific embodiments, including: N-ABD094-rhArg (SEQ ID NO: 50) and certain derivatives, and a limited number of arginine deiminase–based constructs and are enabled for these. However, the claims extend well beyond these embodiments to encompass multiple distinct enzyme classes (arginase, arginine deiminase, arginine decarboxylase), enzymes from various species, polypeptides having at least 99% sequence identity to numerous SEQ ID NOs, multiple half-life extension strategies, and treatment of multiple metabolic disorders and related complications.
The presence of working examples for a limited subset of agents and disease models does not enable the full claimed genus, particularly in an unpredictable art involving in vivo metabolic regulation and behavioral effects.
Applicants argue that inhibition of adipocyte differentiation in vitro using arginine-free media or certain arginine-depleting agents demonstrates that any agent capable of depleting arginine would be effective in the claimed methods. These arguments have been considered but not found persuasive. In vitro inhibition of adipogenesis or mechanistic observations regarding arginine depletion do not reliably predict in vivo outcomes, such as induction of intermittent fasting, changes in feeding behavior, or therapeutic efficacy across diverse metabolic disorders.
Accordingly, applicants’ mechanistic rationale does not eliminate the need for undue experimentation across the full scope of the claims.
Applicants assert that a person of ordinary skill would conclude that “any agent capable of depleting plasma arginine levels” could be used in the claimed methods. The specification does not provide sufficient guidance enabling a skilled artisan to determine, without undue experimentation, which of the many claimed arginine-depleting agents, across different enzyme classes, sequence variants, and fusion constructs, will successfully induce intermittent fasting and treat the recited conditions. Enablement requires more than a generalized hypothesis or mechanistic explanation.
Applicants argue that the quantity of experimentation is only one factor under In re Wands. The Examiner agrees and has considered all Wands factors, including the nature and unpredictability of the invention, the breadth of the claims, the limited guidance provided, and the narrow scope of the working examples. When considered as a whole, these factors support the conclusion that undue experimentation would be required to practice the full scope of the claimed invention.
For the reasons above, applicants’ arguments do not overcome the rejection. While the specification enables certain specific arginine-depleting embodiments, it does not reasonably 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.
Accordingly, the rejection of Claims 1, 3-9, 11-12, 14-15, 17-18, 22-26 under 35 U.S.C. §112(a) is maintained.
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.
Claim 26 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 9803185 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
US Patent No. ‘185 claims “A method of treating a cancer or inhibiting arginine-dependent tumor growth in a subject comprising administering an albumin-binding arginine deiminase fusion protein to the patient weekly or biweekly to reduce the availability of circulating arginine” (see claim 1).
As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy. US Patent. No. ‘185 discloses wherein the arginine level is below 50 µm (see figure 11) and this property is inherent to the drug and the therapeutically effective concentration. US Patent NO. ‘185 claims wherein the arginine depleting agents is an arginine catabolic enzyme and in particular, an arginine deiminase protein (see claim 1). US Patent NO. ‘185 teaches wherein the arginine deiminase protein comprises an albumin binding domain/polypeptide (see claim 1).
Regarding Claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, US Patent No. ‘185 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular arguments with regards to the reference (US Patent No. ‘185) not teaching the same patient population. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claim 26 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. RE48805E1 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18, cited previously).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
US RE48805 claims “A method of treating a cancer or inhibiting arginine-dependent tumor growth in a subject comprising administering an albumin-binding arginine deiminase fusion protein to the patient weekly or biweekly to reduce the availability of circulating arginine” (see claim 1).
As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy. US Patent. No. ‘805 discloses wherein the arginine level is below 50 µm (see figure 11) and this property is inherent to the drug and the therapeutically effective concentration. US Patent NO. ‘805 claims wherein the arginine depleting agents is an arginine catabolic enzyme and in particular, an arginine deiminase protein (see claim 1). US Patent NO. ‘805 teaches wherein the arginine deiminase protein comprises an albumin binding domain/polypeptide (see claim 1).
Regarding claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, US Patent No. ‘805 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular arguments with regards to the reference (US Patent No. ‘805) not teaching the same patient population. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claim 26 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11751050 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18). *All references cited previously.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
US 11751050 claims “ method of treating cancer in a human patient, the method comprising reducing the physiological arginine levels in said patient to below 10 μM combined with administering an anti-neoplastic compound” (see claim 1). US Patent No. ‘050 further clams “the method according to claim 3 wherein said arginine degrading enzyme is arginase, arginine deiminase, arginine decarboxylase, modifications thereof or combinations thereof” and wherein said arginase is pegylated human arginase I. (see claims 4-5).
As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy. US Patent. No. ‘050 discloses wherein the arginine level is below 50 µm (see claim 1) and this property is inherent to the drug and the therapeutically effective concentration.
Regarding claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, US Patent No. ‘050 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular arguments with regards to the reference (US Patent No. ‘050) not teaching the same patient population. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
Claim 26 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 7951366 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18). *All references cited previously.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
US 7951366 B2 claims “ A method of treating human liver, breast, colon or rectal cancer, comprising administering parenterally to a subject in need thereof a modified, full-length recombinant human arginase I polypeptide having an amino acid sequence encoded by a nucleic acid of SEQ ID NO: 8, which wherein said human arginase I is modified by covalent linkage to at least one polyethylene glycol (PEG) molecule, wherein the administration of the modified, full-length recombinant human arginase I polypeptide reduces the physiological arginine level in the subject to below 10 μM for at least 3 days” (see claim 1). US Patent No. ‘366 further clams “the method according to claim 3 wherein said arginine degrading enzyme is arginase” (see claim 1) and wherein said arginase is pegylated human arginase I. (see claims 1-10).
As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy. US Patent. No. ‘366 discloses wherein the arginine level is below 50 µm (see claim 1) and this property is inherent to the drug and the therapeutically effective concentration.
Regarding claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, US Patent No. ‘366 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Applicant’s Arguments
Applicants reiterate the aforementioned arguments with respect to the instant rejection (in particular arguments with regards to the US Patent. ‘366 not teaching the same patient population. The Office’s rebuttal of these arguments remains the same and is incorporated herein by reference.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-9, 11-12, 14-15, 17-18, 22-25 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.
Claim 1 claims “A method of inducing intermittent fasting, modulating autophagy, or inducing intermittent fasting and modulating autophagy resulting in 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..”. In general the claim language is confusing. In particular, the phrase “related complications” renders the claim indefinite because it is unclear what the complications are related to. Specifically, it is unclear whether the “related complications” are: related to the metabolic disorder (i.e., glucose intolerance or insulin resistance), related to obesity, prediabetes mellitus, or type 2 diabetes or related to intermittent fasting, related to modulation of autophagy. As written, the claim does not provide a clear antecedent or causal relationship establishing what condition gives rise to the “related complications,” nor does it define the scope of the complications with reasonable certainty. This is further complication by the language of “associated with”. The term “associated with” merely denotes a relationship or correlation and does not require the presence of the associated condition in the subject unless explicitly recited. The specification describes treatment of steatosis and whitening or brown fat only the context of subjects having obesity, diabetes or prediabetes. However, the term “associated with” does not require this. As a result, it is unclear whether the recited disease must be present in the subject or whether the association merely reflects general correlation. Claims 3-9, 11-12, 14-15, 17-18, 22-25 are also rejected due to their dependence on claim 1 and not clarifying these points of confusion.
Accordingly, one of ordinary skill in the art would not be able to determine the metes and bounds of the claimed subject matter with reasonable certainty.
Claim 3 claims “The method of claim 1, wherein the arginine concentration in the subject's serum is maintained below 50 μM, below 25 μM, below 20 μM, below 10 μM, or below 5 μM.” Claim 3 is rejected under 35 U.S.C. 112(b) as indefinite because it fails to specify the temporal parameters for "maintaining" the recited arginine concentration. It is unclear if the concentration must remain below the threshold continuously, at a specific time point (e.g., peak or trough), or as a daily average following administration. Without a defined duration or measurement window (in the claim or specification), a person of ordinary skill in the art cannot determine with reasonable certainty the metes and bounds of the claimed "maintaining" step. A suggested amendment could be “The method of claim 1, wherein the arginine concentration in the subject’s serum is maintained below 50 µM, below 25 µM, below 20 µM, below 10 µM, or below 5 µM after co-administering the arginine depleting agent and the second therapeutic agent to the subject.”
Claim 7 claims “The method of claim 1, wherein the arginine catabolic enzyme further comprises an albumin binding domain (ABD) or human serum albumin, or a human IgG Fc domain.” However, the claim does not specify whether the albumin binding domain must be additionally introduced into the arginine catabolic enzyme or whether the limitation encompasses arginine catabolic enzymes that already include an albumin binding domain as part of their primary sequence. It is unclear if Applicants are further defining the species in claim 1 or given the “further comprising” suggesting additional binding domains to even species that already have the binding domains in view of the fact that claim 1 encompasses polypeptides that already include an albumin binding domain. The scope of claim 7 is unclear. Accordingly, one of ordinary skill in the art would not be able to determine with reasonable certainty the metes and bounds of the claim.
Claim 8 recites that the arginine catabolic enzyme is “fused to” an albumin binding domain (ABD) [and/or Fc or human serum albumin]. However, the claim does not specify whether the recited fusion requires a newly engineered fusion construct or whether the limitation is satisfied by arginine catabolic enzymes that already include an albumin binding domain as part of their primary amino acid sequence. In view of the fact that claim 1 encompasses polypeptides that inherently include an albumin binding domain, the structural requirements of the “fused to” limitation in claim 8 are unclear. Accordingly, one of ordinary skill in the art would not be able to determine with reasonable certainty the metes and bounds of the claim.
Claim 12 claims “rapamycin (and rapalogs),…” in line 3. Regarding the parenthetical expression “(and rapalogs)", the metes and bounds of claim 12 is rendered vague and indefinite by the parenthetical expression because it is unclear as to whether the limitation is part of the instantly claimed subject matter.
Claim Rejections - 35 USC § 112
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 4 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 1 claims that the arginine depleting agent comprises an arginine catabolic enzyme selected from arginase protein, arginine deiminase protein or an arginine decarboxylase protein and a polypeptide selected from the sequences listed in instant claim 1, all of which encompass arginase protein or arginine deiminase protein. Claim 4 depends on claim 1 and recites “wherein the arginine depleting agent is an arginase protein, an arginine deiminase protein, or an arginine decarboxylase protein”. Claim 4 does not impose any additional structural or functional limitation beyond what is already required by claim 1. The dependent claim merely restates the same enzyme classes already encompassed by claim 1. Thus, claim 4 does not further limit.
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 § 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) 1, 3-7, 12, 14-15, 22, 25-26 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Debosch (WO2020009740A2, priority date of 4/25/20218).
*Regarding the term “intermittent fasting”, it is understood to occur as a physiological result of administering the arginine-depleting agent, rather than as a separate affirmative dietary intervention. The specification demonstrates that administration of the arginine-depleting agent inherently leads to repeated periods of reduced food intake followed by refeeding, i.e., intermittent fasting cycles (see, e.g., paragraphs [0034], [0053]–[0054], and [0076]). Accordingly, for purposes of this rejection, intermittent fasting is treated as an inherent outcome of administering the arginine-depleting agent.
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 claims 1 and 4, 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 1, Debosch teaches administering a second therapeutic agent such as liraglutide (see paragraph 0095) thus meeting the limitations of a glucose lowering agent.
Regarding claim 3, 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 3 given the inherent properties of the arginine depleting compound. Regarding claim 7, Debosch teaches linking the arginine degrading enzyme to Fc or albumin from human serum (see claim 14, also paragraph 0061). Regarding claims 6, 22, 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 5, Debosch additionally teaches one or more PEG groups (see claim 15). Regarding claims 12, 14, 15, 25, Debosch teaches wherein the second therapeutic is metformin which is a biguanide (see paragraph 0149).
Regarding claim 26, 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) which are patients considered in need of inducing intermittent fasting as defined by Applicants (see paragraph 0007 for example). 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 claims 1 and 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, Debosch discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy/in need of fasting (which is obesity and a diabetic patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 3-9, 12, 14-15, 22-26 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).
*Regarding the term “intermittent fasting”, it is understood to occur as a physiological result of administering the arginine-depleting agent, rather than as a separate affirmative dietary intervention. The specification demonstrates that administration of the arginine-depleting agent inherently leads to repeated periods of reduced food intake followed by refeeding, i.e., intermittent fasting cycles (see, e.g., paragraphs [0034], [0053]–[0054], and [0076]). Accordingly, for purposes of this rejection, intermittent fasting is treated as an inherent outcome of administering the arginine-depleting agent.
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 claims 1 and 4, 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 1, Debosch teaches administering a second therapeutic agent such as liraglutide (see paragraph 0095) thus meeting the limitations of a glucose lowering agent.
Regarding claim 3, 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 3 given the inherent properties of the arginine depleting compound. Regarding claim 7, Debosch teaches linking the arginine degrading enzyme to Fc or albumin from human serum (see claim 14, also paragraph 0061). Regarding claims 6, 22, 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 5, Debosch additionally teaches one or more PEG groups (see claim 15). Regarding claims 12, 14, 15, 25, Debosch teaches wherein the second therapeutic is metformin which is a biguanide (see paragraph 0149).
Regarding claim 26, 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) which are patients considered in need of inducing intermittent fasting as defined by Applicants (see paragraph 0007 for example). 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 claims 1 and 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, Debosch discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy/in need of fasting (which is obesity and a diabetic patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Debosch is silent to wherein the arginine depleting enzyme (arginase I or arginine deiminase) is fused to an Albumin binding domain.
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 claims 8-9, 22-24, 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, regarding claim 24, Debosch teaches that the arginine depleting agent can comprise one or more PEG groups (see claim 15).
Claim(s) 1, 3-7, 11-12, 14-15, 17-18, 22, 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Debosch (WO2020009740A2, priority date of 4/25/20218) in view of Berry (Mol Cell Biol . 2009 Jun;29(12):3286-96, Epub 2009 Apr 13).
*Regarding the term “intermittent fasting”, it is understood to occur as a physiological result of administering the arginine-depleting agent, rather than as a separate affirmative dietary intervention. The specification demonstrates that administration of the arginine-depleting agent inherently leads to repeated periods of reduced food intake followed by refeeding, i.e., intermittent fasting cycles (see, e.g., paragraphs [0034], [0053]–[0054], and [0076]). Accordingly, for purposes of this rejection, intermittent fasting is treated as an inherent outcome of administering the arginine-depleting agent.
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 claims 1 and 4, 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 1, Debosch teaches administering a second therapeutic agent such as liraglutide (see paragraph 0095) thus meeting the limitations of a glucose lowering agent.
Regarding claim 3, 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 3 given the inherent properties of the arginine depleting compound. Regarding claim 7, Debosch teaches linking the arginine degrading enzyme to Fc or albumin from human serum (see claim 14, also paragraph 0061). Regarding claims 6, 22, 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 5, Debosch additionally teaches one or more PEG groups (see claim 15). Regarding claims 12, 14, 15, 25, Debosch teaches wherein the second therapeutic is metformin which is a biguanide (see paragraph 0149).
Regarding claim 26, 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) which are patients considered in need of inducing intermittent fasting as defined by Applicants (see paragraph 0007 for example). 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 claims 1 and 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, Debosch discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy/in need of fasting (which is obesity and a diabetic patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Debosch is silent to wherein the secondary therapeutic is retinoic acid (instant claims 11, 17-18).
However, Berry teaches retinoic acid (RA) represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor beta/delta and retinoic acid receptor (see abstract). Berry teaches “RA treatment of obese mice induced expression of PPARbeta/delta and RAR target genes involved in regulation of lipid homeostasis, leading to weight loss and improved insulin responsiveness. RA treatment also restored adipose PPARbeta/delta expression (see abstract).
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (treating diabetes/obesity), in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each
additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two (retinoic acid with arginine depleting agent) each known to be useful for the same purpose (treating diabetes/obesity), with a reasonable expectation that at least here will be an additive effect.
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).
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Claims 1, 3-9, 11-12, 14-15, 17-18, 22-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33-37 of copending Application No. 16/427593 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application 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 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, 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 instant application further claims arginine level below 50 uM (claim 3); fusion to an ABD; retinoic acid (claims 17-18); SEQ ID Nos:49-50m 1010-102, 104 with PEG (claims 23-24); intermittent fasting (Claims 1 and 26).
The co-pending application 16/427593 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). Co-pending Application 16427593 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 49). The sequences of the co-pending application are identical to the instant claims SEQ ID Nos: including Arginase I peptides with ABD.
Co-pending 16/427593 is silent to including an additional therapeutic agent including retinoic acid.
However, Berry teaches retinoic acid (RA) represses obesity and insulin resistance by activating both peroxisome proliferation-activated receptor beta/delta and retinoic acid receptor (see abstract). Berry teaches “RA treatment of obese mice induced expression of PPARbeta/delta and RAR target genes involved in regulation of lipid homeostasis, leading to weight loss and improved insulin responsiveness. RA treatment also restored adipose PPARbeta/delta expression (see abstract).
It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (treating diabetes/obesity), in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious). But see In re Geiger, 815 F.2d 686, 2 USPQ2d 1276 (Fed. Cir. 1987) (“Based upon the prior art and the fact that each of the three components of the composition used in the claimed method is conventionally employed in the art for treating cooling water systems, the board held that it would have been prima facie obvious, within the meaning of 35 U.S.C. 103, to employ these components in combination for their known functions and to optimize the amount of each
additive....Appellant argues... hindsight reconstruction or at best,... obvious to try’.... We agree with appellant.”). One of ordinary skilled in the art would have been motivated to combine the two (retinoic acid with arginine depleting agent) each known to be useful for the same purpose (treating diabetes/obesity), with a reasonable expectation that at least here will be an additive effect.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2-3, 6-10 of copending Application No. 18/416322 (reference application) as evidenced by Yun (see reference above). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
Co-pending Application 18/416322 claims “A method of treating a disease comprising administering PEG modified arginase to an individual…wherein the arginase is human arginase coupled to PEG” (see claim 1). The main utility of the copending application is for treating cancer via arginine deprivation (see abstract, paragraph 0010). As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy.
Regarding claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, Co-pending Application 18/416322 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Claim 26 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. RE47233 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18) in view of Wong (US20140255377 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
US Patent No. ‘233 claims “An albumin-binding arginine deiminase fusion protein comprising a first portion comprising one or two components selected from an albumin-binding domain, an albumin-binding peptide or an albumin-binding protein(s) fused to a second portion comprising arginine deiminase to form the albumin-binding arginine deiminase fusion protein, and one or more linker molecules; the first portion being positioned far from active site of the second portion by said linker molecule such that the albumin-binding arginine deiminase fusion protein retains the activity of arginine deiminase and binds serum albumin with neither function of one portion of the fusion protein being interfered with by the other portion of the fusion protein, wherein pegylation of said arginine deiminase is avoided, and wherein the albumin-binding arginine deiminase fusion protein comprises a sequence selected from SEQ ID NO: 36, 37, 38, 39, 40, or 41.” (see claim 1). The main pharmaceutical utility of US Patent No. ‘233 is treating cancer (see abstract). Nevertheless, use of arginine deiminase is well known for treating cancer. Wong discloses a method of treating arginine-dependent diseases (see claim 17) including cancer (see abstract) 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 use the arginine deiminase of ‘233 for treating cancer. One of ordinary skill in the art would have been motivated to do so because arginine deiminase and arginine depletion is well known in the art as an effective treatment for cancer. There is a reasonable expectation of success given that Wong teaches treatment of cancer with arginine deiminase.
As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy.
Regarding Claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, US Patent No. ‘233 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Claim 26 remains rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9255262 as evidenced by Yun (International Journal of Molecular science, 2018, 19, pages 3-18) in view of Wong (US20140255377 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims are drawn to “A method of inducing intermittent fasting in a subject in need thereof, the method comprising the step of administering a therapeutically effective amount of an arginine depleting 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 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, SEQ ID NO: 104 or SEQ ID NO: 107; and intermittent fasting comprises intermittent fasting cycles, wherein each intermittent fasting cycle comprises a fasting period and a refeeding period” (claim 26).
US Patent No. ‘262 claims “An albumin-binding arginine deiminase fusion protein comprising a first portion comprising one or two components selected from an albumin-binding domain, an albumin-binding peptide or an albumin-binding protein(s) fused to a second portion comprising arginine deiminase to form the albumin-binding arginine deiminase fusion protein, and one or more linker molecules; the first portion being positioned far from active site of the second portion by said linker molecule such that the albumin-binding arginine deiminase fusion protein retains the activity of arginine deiminase and binds serum albumin with neither function of one portion of the fusion protein being interfered with by the other portion of the fusion protein, wherein pegylation of said arginine deiminase is avoided, and wherein the albumin-binding arginine deiminase fusion protein comprises a sequence selected from SEQ ID NO: 36, 37, 38, 39, 40, or 41.” (see claim 1). The main pharmaceutical utility of US Patent No. ‘262 is treating cancer (see abstract). Nevertheless, use of arginine deiminase is well known for treating cancer. Wong discloses a method of treating arginine-dependent diseases (see claim 17) including cancer (see abstract) 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 use the arginine deiminase of ‘262 for treating cancer. One of ordinary skill in the art would have been motivated to do so because arginine deiminase and arginine depletion is well known in the art as an effective treatment for cancer. There is a reasonable expectation of success given that Wong teaches treatment of cancer with arginine deiminase.
As evidenced by Yun and claim 2, cancer is considered a patient population in need of modulating autophagy.
Regarding Claim 26, “inducing intermittent fasting and/or modulating intermittent fasting resulting in increasing longevity and intermittent fasting cycles comprising a fasting period and a refeeding period …”, in the instant case, US Patent No. ‘262 discloses administering the same arginine depleting agent of the instant claims to the same subject in need of modulating autophagy (which is a cancer patient) and thus would inherently result the above result oriented effects. The periods of fasting and refeeding are inherent to administering the compound which induces periods of fasting (not wanting to eat) which would also induce periods of feeding (desire to eat in the subject administered the drug).
Conclusion
No claims are allowed.
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/ERINNE R DABKOWSKI/Examiner, Art Unit 1654