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 Response of 4 Dec. 2025 has been entered.
Claims 1-14, 17-21, 25 and 27 are currently pending.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows: The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63442774, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In particular, the ‘774 provisional application does not provide support for a method of treatment as instantly claimed wherein the administered uricase enzyme is cross-linked with PEG of any size (the ‘774 application is limited to PEG of 2-3.5 kDa in size, as recited in claim 7; see ‘774, p. 3, line 20 to p. 5, line 19; p. 6, lines 7-9; p. 10, line 28 to p. 11, line 3; Examples). The ‘774 application also fails to disclose the range of greater than or equal to 4.5 mg/dL in claim 21. As such, the effective filing date for claims 1-6, 8-14, 17, 18, 20, 21, 25 and 27 is that of the instant application, i.e. 1 Feb. 2024. Claim 7 has an effective filing date of that of the ‘774 application, i.e. 2 Feb. 2023.
Election/Restrictions
Applicant’s election of the species of: gout as the disease/disorder; E4W as the frequency of administration and 36 mg as the dosage in the reply filed on 4 Dec. 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). In the interest of compact prosecution, the species election requirements relating to species of frequencies and species of dosages are withdrawn.
Claims 1-14, 17-21, 25 and 27 are considered here with respect to the elected species of gout.
Claim Rejections - 35 USC § 103
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.
Claims 1-6, 9-14, 17-19 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over WO2022097141 to Ruderfer et al. (cited in IDS of 4 Aug. 2024).
Regarding claims 1, 18 and 19, Ruderfer teaches a method of treating gout (a disease or disorder associated with excessive uric acid levels) in a subject in need thereof, comprising administering to the subject by i.v. infusion an effective amount of a recombinant homotetrameric uricase enzyme comprising four uricase polypeptides having the amino acid sequence as set forth in SEQ ID NO: 2, wherein said polypeptides are crosslinked by polyethylene glycol (PEG) bis-aldehyde having a molecular weight of about 2-3.5 kDa (p. 3, line 15 to p. 7, line 10; p. 19, lines 13—17; p. 21, lines 1-32; p. 24, line 21 to p. 25, line 7; p. 35, line 26 to p. 36, line 8; p. 38, lines 7-10). SEQ ID NO: 2 of Ruderfer is 100% identical to SEQ ID NO: 2 of the instant claims (see attached alignment).
Regarding the recitation that the administering is “no more than once every four weeks” in claim 1 and every 4, 6, 8, 10 or 12 weeks in claims 2-6, 9-13 and 27, Ruderfer teaches that the method can use a dosing interval ranging from at least one week to at least three months, including e.g. one month (about 4 weeks), two months (about 8 weeks) or three months (about 12 weeks) (p. 41, lines 9-17). Since Ruderfer teaches administering the same drug to treat the same condition as in the claimed method, it would have been obvious for one of ordinary skill in the art to use routine experimentation to discover the optimum and/or workable range of dosing interval within the general range taught by Ruderfer (see MPEP 2144.05). Moreover, Ruderfer teaches that the dosage interval is a result-effective variable which can be adjusted to achieve/maintain a desired therapeutic effect (p. 40, lines 20-33). Such result-effective variables are not given patentable weight absent evidence of criticality relating to the specific values claimed (see MPEP 2144.05), which evidence has not been presented here.
Regarding the dosages of 1 mg, 2 mg, 3 mg, 4 mg, 8 mg, 12 mg, 16 mg, 18 mg, 24 mg, 36 mg or 48 mg per subject in claims 1-6 and 27, Ruderfer teaches that the dosage can be 1 mg, 2 mg, 4 mg, 6 mg, 8 mg, 10 mg, 12 mg, 16 mg, 24 mg, 40 mg or 60 mg per month per subject (p. 41, line 18 to p. 42, line 2). Assuming a one month dosing interval (see above), Ruderfer teaches a range of doses that effectively encompasses the range recited in the claims. Since Ruderfer teaches administering the same drug to treat the same condition as in the claimed method, it would have been obvious for one of ordinary skill in the art to use routine experimentation to discover the optimum and/or workable range of dosage within the general range taught by Ruderfer (see MPEP 2144.05). Moreover, Ruderfer teaches that the dosage is a result-effective variable which can be adjusted to achieve/maintain a desired therapeutic effect (p. 39, line 32 to p. 40, line 33). Such result-effective variables are not given patentable weight absent evidence of criticality relating to the specific values claimed (see MPEP 2144.05), which evidence has not been presented here.
Regarding claim 14, Ruderfer teaches that the recombinant enzyme can be plant recombinant enzyme (p. 25, lines 3-7).
Claims 8, 17 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over WO2022097141 to Ruderfer et al., as applied to claims 1-6, 9-14, 17-19 and 27, in view of US20220023394 to Botson.
Claims 8, 17 and 20 differ from Ruderfer, as applied to claims 1-6, 9-14, 17-19 and 27, in that: the uricase is administered over a period of about 1, 1.5, 2 or 3 hours (claim 8); the method further comprises administration of methotrexate to said subject (claim 17); the subject has sever gout or refractory gout; and/or the gout is erosive or tophaceous gout (claim 20).
Botson teaches a method of treating gout, including refractory gout, comprising administering a tetrameric PEG-modified uricase such as Peglitocase ([0070]-; cf. instant Spec. US20240263150, [0008] describing Peglitocase as a tetrameric PEGylated uricase). Botson teaches that immunogenic reactions to the PEG-uricase can be reduced by i) administering the uricase over a course of about 15-175 mins., wherein the total dose can range from about 7-50 mg at a dosing frequency that can range from about 1-3 months; and/or ii) administering an anti-inflammatory agent such as methotrexate to the subject ([0003]-[0032]; [0070]-[0146]).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Ruderfer to treat gout by administering a tetrameric PEG-uricase wherein the subject has refractory gout and the subject is further administered an anti-inflammatory agent such as methotrexate as taught by Botson because it would have been obvious to combine prior art elements according to known methods to yield predictable results. One of ordinary skill would have been motivated to use the method of Ruderfer to treat refractory gout and to further administer methotrexate to the subject because Botson teaches that PEG-uricase are highly effective for treating refractory gout but suffer from immunogenicity in some subjects (e.g., [0002]), which can be addressed via administration of methotrexate. Using the method of Ruderfer to treat refractory gout and further administering methotrexate to the subject as taught by Botson would have led to predictable results with a reasonable expectation of success because the method of Botson is substantially similar to that of Ruderfer, involving administering the same general type of medicament (tetrameric PEGylated uricase) to treat the same disease (gout) as in the claimed method.
Regarding claim 8, Botson teaches administering the same general type of medicament (tetrameric PEGylated uricase) in the same amounts and dosing frequency to treat the same disease as in the claimed method, it would have thus been obvious for one of ordinary skill in the art to use routine experimentation to discover the optimum and/or workable range of duration within the general range taught by Botson (see MPEP 2144.05). One of ordinary skill would have had a reasonable expectation of success in using a duration of about 1, 1.5, 2 or 3 hours as in claim 8 because Botson teaches a range of duration (~15-175 mins) that encompasses and substantially overlaps the claimed values.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over WO2022097141 to Ruderfer et al., as applied to claims 1-6, 9-14, 17-19 and 27, in view of Sarawate et al., Journal of Clinical Rheumatology 12.2 (2006): 61-65.
Claim 21 differs from Ruderfer, as applied to claims 1-6, 9-14, 17-19 and 27, in that: the subject has a serum urate level of ≥ 4.5 mg/dL, ≥ 6 mg/dL or ≥ 7 mg/dL (claim 21).
Sarawate teaches that the biochemical basis of gout is supersaturation of serum urate (SUA) resulting in precipitation of urate crystals, and that the target goal recommended in treatment of gout is to lower the SUA to the subsaturating range of less than 6.0 mg/dL (p. 61, 2nd ¶).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Ruderfer to treat gout by administering a tetrameric PEG-uricase wherein the subject has a serum urate ≥ 6 mg/dL because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Using the method of Ruderfer to treat gout by administering a tetrameric PEG-uricase wherein the subject has a serum urate ≥ 6 mg/dL would have led to predictable results with a reasonable expectation of success because Sarawate teaches that the biochemical basis of gout is supersaturation of serum urate (SUA) and that the target goal recommended in treatment of gout is to lower the SUA to the subsaturating range of less than 6.0 mg/dL (making it prima facie obvious to treat any subject having serum urate ≥ 6 mg/dL).
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over WO2022097141 to Ruderfer et al., as applied to claims 1-6, 9-14, 17-19 and 27, in view of Macovei et al., The Medical-Surgical Journal 119.1 (2015): 62-68.
Claim 25 differs from Ruderfer, as applied to claims 1-6, 9-14, 17-19 and 27, in that: the subject has had two or more gout flares over the past year and/or has persistent joint inflammation (claim 25).
The teachings of Ruderfer are set forth above. Regarding claim 25, Ruderfer further teaches administering an “effective amount” of the uricase, which means “an amount of modified uricase effective to prevent, alleviate or ameliorate symptoms of [the] disease” being treated (p. 39, lines 29-31).
Macovei teaches that gout is characterized by symptoms including episodic or persistent joint inflammation (p. 62, 2nd ¶).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use the method of Ruderfer to treat gout by administering a tetrameric PEG-uricase wherein the subject has persistent joint inflammation because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Using the method of Ruderfer to treat gout by administering a tetrameric PEG-uricase wherein the subject has persistent joint inflammation would have led to predictable results with a reasonable expectation of success because Ruderfer teaches treating gout by administering an effective amount of the PEG-uricase sufficient to treat symptoms of the disease, and Macovei teaches that persistent joint inflammation is a characteristic symptom of the disease.
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 1-14, 17-21, 25 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50-52, 54-63 and 65-77 of copending Application No. 18035149, in view of Ruderfer, Botson, Sarawate and/or Macovei. The claims of the ‘149 application teach essentially the same PEG-uricase as in the instant claims, comprising a tetrameric PEG-uricase comprising bifunctional PEG linking moieties of about 2-4 kDa and a uricase of SEQ ID 2 (which is 100% identical to instant SEQ ID 2), and Ruderfer teaches treating gout with such PEG-uricase at the dosages, frequencies and durations recited in the instant claims (see 103 rejection, above). Moreover, Botson, Sarawate and/or Macovei teach and render obvious the limitations of claims 8, 17, 20, 21 and 25 (see 103 rejection, above).
This is a provisional nonstatutory double patenting rejection.
Claims 1-14, 17-21, 25 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of copending Application No. 19202015. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘015 app teach a method of treating gout be administering the same PEG-uricase as in the instant claims, comprising bifunctional PEG linking moieties of about 2-3.6 kDa and a uricase of SEQ ID 2 (which is 100% identical to instant SEQ ID 2). The ‘015 claims further teach: the frequency of administration (once every 4, 6, 8, 10 or 12 weeks), dosage (1 mg, 2 mg, 3 mg, 4 mg, 8 mg, 12 mg, 16 mg, 18 mg, 24 mg, 36 mg or 48 mg per subject) and duration of administration (1, 1.5, 2 or 3 hours) recited in claims 1-6, 8-13 and 27 (‘015, claims 1-4); the formulation buffer, 2 mg/ml concentration and plant recombinant enzyme of clam 14 (‘015, claims 5-7); administration of methotrexate as in claim 17 (‘015, claim 8); and the conditions, symptoms and urate levels of claims 20, 21 and 25 (‘015, claims 10-12). The claims of the ‘015 app thus anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/ROBERT J YAMASAKI/Primary Examiner, Art Unit 1657