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 10, 2026 is acknowledged. Claims 1-32 were cancelled, claims 33-34 were amended, claims 33-37 are pending.
*This office action is made second non-final because, upon consideration of applicants arguments regarding the effect of prior art date of DeBosch, the examiner agrees that the provisional application does not provide support for all the subject matter previously relied upon. Accordingly, the prior art rejection has been modified to rely only on subject matter entitled to the earlier priority date and, wherein appropriate, On additional prior art to address the remaining claim limitations. A second non-final office section is therefore warranted.
Election/Restrictions
The restriction requirement was deemed proper and made FINAL previously. The presently pending claims are directed solely to the election invention; therefore, examination is directed to that invention. The election of species requirement is withdrawn. Claims 33-37 are examined on the merits of this office action.
Withdrawn Objections/Rejections
The objection to claims 33-34 are withdrawn in view of amendment of the claims August 10, 2026.
The rejection of Claims 33-37 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, scope of enablement is withdrawn in view of amendment of the claims August 10, 2026.
The rejection of claim(s) 33-36 under 35 U.S.C. 102(a)(1) as being anticipated by Debosch (WO2020009740A2, priority date of 4/25/20218) is withdrawn in view of Applicants arguments filed August 10, 2026 (with regard to the priority date of Debosch, see above description).
The rejection of claim(s) 33-37 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over Debosch (WO2020009740A2, priority date of 4/25/20218) in view of Wong (US20140255377 A1, cited previously) is withdrawn in view of Applicants arguments filed August 10, 2026 (with regard to the priority date of Debosch, see above description).
Maintained/revised Rejections
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 33-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-9, 11-12, 14-15, 17-18, 20, 22-30 of copending Application No. 17247153 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims “A method of reducing serum arginine comprising:administering a therapeutically effective amount of an arginine depleting agent to a subject with who is 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, or the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, or SEQ ID NO: 104;wherein administration of the arginine depleting agent depleting serum arginine in the subject maintains an arginine concentration in the subject's serum below 50 pM (claim 33). The instant application further claims wherein the arginase protein, arginine deiminase protein, or arginine decarboxylase protein further comprises an albumin binding domain or human serum albumin, or a human IgG Fc domain (claim 34); wherein the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO:101, SEQ ID NO: 102, SEQ ID NO: 103, or SEQ ID NO: 104 (claims 35); wherein the arginine catabolic enzyme comprises a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, or SEQ ID NO: 104, wherein SEQ ID NO: 101, SEQ ID NO:102, SEQ ID NO: 103, and SEQ ID NO: 104 further comprise one or more polyethylene glycol (PEG) groups (claim 36); wherein the arginine catabolic enzyme consists of SEQ ID NO: 49, SEQ ID NO: 50, or SEQ ID NO: 101 with one or more polyethylene glycol (PEG) groups (claim 37).
Co-pending Application 17/247153 claims “A method of reducing serum arginine…, 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 subject has prediabetes, diabetes, obesity… wherein the arginine depleting agent comprises an arginine catabolic enzyme selected from Homo sapiens (human) arginase I, Bacillus caldovelox arginase, Thermus thermophilus arginase, and Sus scrofa arginase I, Mycoplasma hominis arginine deiminase Mycoplasma arginine arginine deiminase, and Mycoplasma arthritis arginine deiminase and a polypeptide having at least 99% sequence homology with SEQ ID NO: 49, SEQ ID NO: 50, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, SEQ ID NO: 54, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 69, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 72, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO:103, SEQ ID NO: 104 or SEQ ID NO: 107; and the second therapeutic agent is selected from the group consisting of an autophagy inducing agent, a glucose lowering agent, a retinoid derivative, an (-)-epigallocatechin-3-gallate (EGCG) derivative, and a rapamycin derivative” (claim 1). The co-pending application further claims arginine level below 50 uM (claim 1); fusion to an ABD or FC (Claim 7); SEQ ID Nos:49-50, 101-102, 104 with PEG (claims 23-24).
The sequences of the co-pending application are identical to the instant claims SEQ ID Nos: including Arginase I peptides with ABD.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Applicant’s Arguments
Applicant states “The Examiner's valid concerns relating to Applicant's copending application is noted. However, as neither application has been allowed and the claimed subject matter is still not final, Applicant respectfully submits that a terminal disclaimer can be submitted at a later time if conflicting subject matter is still present.”
Applicants arguments have been fully considered but not found persuasive. As the conflicting subject matter remains pending the provisional non statutory double pending rejection is maintained.
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., Changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 33 is/are rejected under 35 U.S.C. 103 as being unpatentable over Debosch (WO2020009740A2, priority date of 4/25/20218) in view of Min (WO2002009741 A1, cited previously).
Applicants arguments concerning the effective prior art date of DeBosch have been fully considered and are persuasive to the extent that the April 25th, 2018 provisional application does not provide support for the full scope of the subject matter disclosed in the subsequently filed DeBosch application. Subject matter relied upon from a reference is entitled to the benefit of an earlier provisional filing date only to the extent that the provisional application provides the requisite support for that subject matter (see MEPE 2136.03). Upon reconsideration, the examiner finds that the DeBosch provisional application provides support for pegylated arginine deaminase (ADI-PEG) as an arginine depleting agent and its use in treating metabolic disorders including diabetes, obesity, metabolic syndrome and NAFLD. The provisional application additionally provides support for increasing arginine's activity in the treatment of metabolic disease, including overexpression of Arg2 in hepatocytes and the resulting improvement in energy homeostasis and reduction in fat accumulation, and further suggest Arg1 over expression. Accordingly, DeBosch is relied upon as of April 25th, 2018 provisional filing date only for those supported teachings.
Regarding claim 33, DeBosch teaches treating metabolic disease by depletion of arginine and in particular, teaches administration of a therapeutically effective amount of pegylated arginine deiminase (ADI-PEG) for treating metabolic disorders including diabetes and obesity (see claim 1-2, see paragraph 0031, Example 2). Debosch suggests use of increased expression of ArgI/ArgII (see Figure 9, Figure 11, Figure 1). Thus, DeBosch teaches administering an arginine depleting agent, arginine deiminase, to the same type of subject and for the same therapeutic purpose recited an instant claim 33 reduce arginine.
DeBosch however, does not identify the organism from which the arginine deiminase used in its ADI-PEG treatment is obtained and therefore does not expressly teach the presently claimed Mycoplasma argininii arginine deiminase.
However, Min teaches an arginine deiminase obtained from Mycoplasma arginini. In particular, example 1 of Min describes isolation and purification of arginine deiminase from Mycoplasma arginini, Including culturing M. arginini, disrupting the cells, and purifying the arginine deiminase. Min further determines the enzymatic activity of the purified enzyme based upon conversion of arginine to citrulline. Example 2 further describes cloning and recombinant expression of the M. arginini arginine deiminase. Min thus expressly identifies M. arginini as a source of an active arginine depleting arginine deiminase. Min additionally teaches modification of arginine deiminase by conjugation to an activated polymer to improve its properties for therapeutic administration. In particular, Min teaches that the polymer may be peg and explains that the polymer conjugation may increase the in vivo half life of the enzyme and reduce immunogenicity. This teaching is also expressly reflected in claims 3, 6, 7 of Min, wherein claim 3 specifies arginine deiminase from M. arginini, claim 6 claims arginine deiminase conjugated to a polymer and claim 7 specifies PEG.
It would have been obvious before the effect of filing date of the claim invention to employ the M. arginini arginine deiminase taught by Min as the arginine deiminase in the ADI-PEG treatment taught by DeBosch. DeBosch Features the therapeutic use of pegylated arginine deiminase to deplete arginine for treatment of the claimed metabolic disorders but does not specify the source of the arginine deiminase. Min expressly teaches M. arginini as a source of active arginine deiminase and further teachers peg conjugation of arginine deiminase for therapeutic use. Thus, one of ordinary skill in the art would have had a reason to select Min’s M. arginini arginine deiminase for use as the ADI in DeBosch’s ADI-PEG treatment. One of ordinary skill in the art would have further had a reasonable expectation of success because Min demonstrates isolation and enzymatic activity of M. arginini arginine deiminase and teaches both for common at production of the enzyme and its conjugation to peg. The resulting combination would therefore provide a pegylated M. arginini arginine deiminase capable of depleting arginine for use in treating the metabolic disorders taught by Debosch. Therefore, DeBosch in view of Min teaches or suggests administering a therapeutically effective amount of an arginine agent to a subject having the claim metabolic disorder, wherein the Argentine depleting agent comprises M. arginini arginine deiminase, as recited in instant claim 33.
Regarding claim 33, “reducing serum arginine …”, and a serum arginine concentration below 50 µM, in the instant case, Debosch in view of Min discloses administering the same arginine depleting agent of the instant claims to the same subject population (patients with diabetes and obesity) and thus would inherently result the above result oriented effects.
Claim(s) 34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Debosch (WO2020009740A2, priority date of 4/25/20218) in view of Min (WO2002009741 A1, cited previously) as applied to instant claim 33 above, in further view of Wong (US20140255377 A1, cited previously).
The teachings of DeBosch in view of Min are described in the above rejection.
Debosch in view of Min is silent to wherein the arginine depleting enzyme is fused to an Albumin binding domain.
However, Wong discloses a method of treating arginine-dependent diseases (see claim 17) comprising administering a therapeutically effective amount of an arginine depleting agent fused to albumin binding domain (see claims 15 and 1). Wong teaches wherein the arginine level is below 50 µm (see figure 11). Wong teaches wherein the arginine depleting agents is an arginine catabolic enzyme and in particular, an arginine deiminase protein (see claim 1). Wong teaches fusing an albumin binding domain to the arginine depleting agent to create high activity and prolonged half life (see abstract).
It would have been obvious before the effect of filing date of the claim invention to substitute the albumin binding domain modification taught by Wong for the peg modification taught by Debosch and Min. Both modifications serve the known and predictable function of prolonging the circulating half-life from an arginine depleting therapeutic agent. A person of ordinary skill seeking to provide a longer circulating arginine depleting agent for the metabolic treatment taught by Debosch therefore would have had reason to employ Wongs albumin binding domain approach as an alternative to pegylation. One of ordinary skill in the art would have had a reasonable expectation of success because Wong teaches that fusion of an arginine depleting agent to an albumin binding domain provides an active arginine depleting construct having prolonged circulation half-life. The substitution would therefore have amounted to the use of a known alternative half-life extension technique for its established function, while retaining the arginine depending activity and therapeutic purpose taught by DeBosch.
Claim(s) 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Debosch (WO2020009740A2, priority date of 4/25/20218, cited previously) in view of Min (WO2002009741 A1, cited previously) as applied to instant claim 33 above, in further view of Wong (US20140255377 A1, cited previously) as applied to claim 34 above in further view of Cheng (WO2004000349 A1).
The teachings of DeBosch in view of Min and Wong are described in the above rejection.
Regarding claim 35, Debosch teaches that arginine depletion is useful for treating metabolic disorders including obesity, diabetes, metabolic syndrome and NAFLD and further teaches the increased arginase activity provides beneficial metabolic effects. DeBosch further suggests increasing Arg1 Activity is an approach for treating metabolic disease. DeBosch, however, does not teach administration of the particular human arginase I protein recited in instant claim 35.
Cheng teaches recombinant human arginase 1 as a therapeutic arginine defeating agent. In particular, Cheng administration of a recombinant human arginase I to a subject for the purpose of reducing arginine levels. Cheng further teaches conjugation of human arginase I to PEG and teaches administration of Pegylated human arginase I reduces arginine levels (see claims 1-27). Cheng teaches recombinant human Arginase I and provides the amino acid sequence of human arginase 1 in figure 2B. The amino acid sequence of the human arginine 1 disclosed in figure 2B of Cheng is identical to instant SEQ ID NO:103 of the instant application. Accordingly, Cheng establishes that the human ARG1 recited in the present claims was known in the art as being capable of being an arginine depleting therapeutic agent and that pegylated ArgI was known to provide sustained depletion of physiological arginine.
It would have been obvious before the effective filing date of the claim invention to employ the recombinant human Arg I taught by Cheng as the arginine depleting agent in the metabolic disease treatment taught by DeBosch. DeBosch teaches that arginine depletion is beneficial for treating the claimed metabolic disorders and further teaches that increasing arjuna's activity produces beneficial metabolic effects and suggests ARG1 over expression. Cheng provides a known therapeutic means for implementing arginine depletion using human ARG1 by teaching administration of the same human ARG1 sequence recited in the claims to systemically deplete physiological arginine. One of ordinary skill therefore would have had a reason to use Cheng’s human Arg1 in the treatment taught by Debosch, with a reasonable expectation that It would successfully deplete arginine in vivo and thereby provide the arginine depletion related metabolic benefits taught by Debosch. This is further strengthened by the fact that Cheng demonstrates that administered recombinant human Arg1 retains activity and reduces arginine levels for at least three days.
Regarding claims 35-37, instant SEQ ID NO:49 is an ABD linked to human arginase I with a 6XHis tag. Debosch in view of Min, Wong and Cheng 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). Cheng teaches the human arginase I peptide found in instant SEQ ID NO:49 and SEQ ID NO:103 (see Figure 2B). Thus, the combined teachings of Debosch in view of Min, Wong and Cheng teach instant SEQ ID NO:49. Furthermore, Debosch, Min and Cheng teach that the arginine depleting agent can comprise one or more PEG groups (see claim 15).
Regarding claim 33, “reducing serum arginine …”, and a serum arginine concentration below 50 µM, in the instant case, the combined references of Debosch in view of Min and Cheng discloses administering the same arginine depleting agent of the instant claims to the same subject population (patients with diabetes and obesity) and thus would inherently result the above result oriented effects.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
