DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1 and 20-28 are pending.
Election of Invention
Applicants’ election of the species of a method of treating gout and additional step of measuring anti-PEG antibody (see page 5 of Remarks filed on 05/20/2026), is acknowledged and entered.
Applicants’ amendments filed on 05/20/2026, have been entered into the record. Applicants have amended claim 1. Applicants have cancelled claims 2-19. Applicants have newly added claims 20-28. Therefore, claims 1 and 20-28 are subject of the Office action below.
Priority
Applicants’ amendments filed on 10/04/2023, is a CON of U.S. Application No. 16/777,634, filed on 01/30/2020 (ABN), which claims a priority to U.S. Provisional Application Nos: i) 62/903,567, filed on 09/20/2019; and ii) 62/798,783, filed on 01/30/2019.
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 and 20-28 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 20-28 depend from claim 1 and are therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the reasons set forth below.
As per MPEP 2173.02, “[d]uring prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude (emphasis added). See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc).”
If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, is appropriate (emphasis added). See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993).
Claim 1 recites the limitation of “the end of pegloticase treatment”, however, a person of the ordinary skill in the art cannot reasonably determine the meets and bounds of the recited limitation in claim 1. This is because the term “the end of pegloticase treatment”, is a relative term which renders the claim indefinite in that it is not defined by the claim and the specification does not provide a standard for ascertaining the requisite degree. Claim 1 only requires intravenously administering 8 mg of pegloticase every 2 weeks without a time frame for the termination of pegloticase therapy. Thus, a person skilled in the art would not be able to draw a clear boundary between what is and is not covered by the claim. For the purpose of examination, any time frame for the termination of pegloticase therapy, is included in the interpretation of “the end of pegloticase treatment”. Appropriate correction is required.
Claim 28 recites “the first dose” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 28 lacks antecedent basis because, claim 1 from which claim 28 depends, fails to recite “a first dose”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 20-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrials.gov Identifier NCT03303989 (hereinafter “NCT03303989”, available 10/06/2017).
By way of a background, Applicants’ invention (see, e.g., ¶ 0009 of the specification), is drawn to a method for treating gout with a combination therapy comprising pegloticase and mycophenolate mofetil (MMF), which is an immune suppressive agent. Pegloticase (Cell Cept or Krystexxa, KXX), is a monomethoxy polyethylene glycol (mPEG) linked uricase (mPEGylated uricase), which is known in the art for reducing serum uric acid levels in patients with gout (see ¶s 0004 and 0027 of the specification).
Independent claim 1 is directed to a method for treating gout comprising the steps of:
a) administering 500 mg twice/day of MMF orally;
b) co-administering 8 mg of pegloticase intravenously every 2 weeks and 1000 mg twice/day of MMF orally until the end of pegloticase treatment.
Similar to the Applicants’ invention (see discussions above), NCT03303989 relates to a phase II clinical trial study of a combination therapy (comprising pegloticase and MMF), for treating patients with chronic refractory gout, in order to significantly and safely attenuate immunogenicity to pegloticase and ensure patients afflicted with chronic refractory gout have better treatment outcomes and improved quality of life. Please see “Study Description” section on page 2/11. Pegloticase is also known by other names (Cell Cept or Krystexxa). Please see pages 5/11-6/11.
Specifically, NCT03303989 (see “Intervention/treatment” section on page 5/11), discloses:
a) administering 500 mg twice/day of MMF orally;
b) co-administering 8 mg of pegloticase intravenously every 2 weeks and 1000 mg twice/day of MMF orally for 12 weeks (6 doses of pegloticase) and continue pegloticase therapy for adiitional 3 months (12 weeks, i.e., additional 6 doses of pegloticase therapy), for a total 12 doses of pegloticase therapy.
Treatment outcome is aimed at lowering serum uric acid (SUA, serum urate) to ≤ 6 mg/dL (see page 3/11).
The gout patients have serum uric acid level of > 6 mg/dL (20 patients 8.9 ± 1.8 mg/dL; 10 patients 9.8 ± 1.3 mg/dL; and 32 patients 9.2 ± 1.7 mg/dL). Please see page 11/19.
Therefore, claim 1 is anticipated by NCT03303989.
Regarding claim 20, NCT03303989 discloses 12 doses of pegloticase therapy (see discussions above).
Regarding claims 21-22, NCT03303989 teaches patients’ serum uric acid level of >6 mg/dL, measured before infusion (see discussions above).
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.
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.
Claims 1 and 20--24 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03303989 (available 10/06/2017) as applied to claims 1 and 20--22 above.
The limitation of claims 1 and 20-22, as well as the corresponding teachings of NCT03303989, are described above and are hereby incorporated into the instant rejection.
The invention of claims 23-24 are similar to claim 22, however, claims 23-24 differ slightly from 22 in that claims 23-24 further require discontinuation of treatment, when two consecutive measurements of the SUA are above 6 mg/dL.
NCT03303989 is not explicit in teaching the limitation of claims 23-24.
However, the invention of claims 23-24 would have been obvious over NCT03303989. This is because NCT03303989 teaches that: i) gout patients have SUA level of > 6 mg/dL (see discussions above); and ii) treatment outcome is aimed at lowering SUA to ≤ 6 mg/dL (see discussions above). A person skilled in the art would have understood that treated gout patients showing measurements of the SUA are above 6 mg/dL, would be considered as treatment resistant or non-responsive patients.
Therefore, a person skilled in art would have found obvious to discontinue treatment in treatment resistant or non-responsive patients.
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1, 20-22 and 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03303989 (available 10/06/2017) as applied to claims 1 and 21-22 above, and in view of Freyne (Transplantation Proceedings, 2018, 50, 4099-4101).
The limitation of claims 1 and 20-22, as well as the corresponding teachings of NCT03303989, are described above and are hereby incorporated into the instant rejection.
The invention of claims 25-26 are similar to claim 1, however, claims 25-26 differ slightly from 1 in that claims 25-26 further require administering prednisone.
NCT03303989 is not explicit in teaching prednisone.
However, the claimed invention would have been obvious over NCT03303989 because prednisone was known in the art as an immunosuppressant that can be used for reducing immunologic response to pegloticase therapy.
For example, Freyne discloses that a therapy comprising MMF, prednisone and pegloticase, was found to result in the reduction of immunologic response to pegloticase therapy. The patient did not report any gout flares and also reported improved mobility, pain, and quality of life on completion of therapy. Please see abstract and discussions therein.
Therefore, at the time of the instant invention, a person skilled in the art would have found it obvious to modify NCT03303989 with Freyne, in order to arrive at the invention of claims 25-26. One skilled in the art would have had a reasonable expectation that a therapy comprising MMF, pegloticase and prednisone, would exhibit an enhanced reduction of immunologic response to pegloticase therapy, when compared to a therapy comprising only MMF and pegloticase.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1, 20-22 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03303989 (available 10/06/2017) as applied to claims 1 and 21-22 above, and in view of Freyne (Transplantation Proceedings, 2018, 50, 4099-4101).
The limitation of claims 1 and 20-22, as well as the corresponding teachings of NCT03303989, are described above and are hereby incorporated into the instant rejection.
The invention of claim 27 similar to claim 1, however, claim 27 differs slightly from 1 in that claim 27 further requires administering colchicine.
NCT03303989 is not explicit in teaching colchicine.
However, the claimed invention would have been obvious over NCT03303989 because colchicine was known in the art as a symptomatic treatment of gout patients with CKD.
For example, Freyne method for treating gout in a patent with CKD, with a therapy comprising MMF, colchicine and pegloticase, wherein colchicine was employed as a prophylactic for gout flares, which are often precipitated by dramatic changes SUA levels in either direction. Please see “CASE REPORT” section on page 4100. Colchicine was known in the art as a symptomatic treatment of gout patients with CKD (see page 4099).
Therefore, at the time of the instant invention, a person skilled in the art would have found it obvious to modify NCT03303989 with Freyne, in order to arrive at the invention of claim 27. One skilled in the art would have had a reasonable expectation that a therapy comprising MMF, colchicine and pegloticase, would exhibit an enhanced reduction of gout flares, which are often precipitated by dramatic changes SUA levels in either direction.
Obviousness requires only a reasonable expectation of success, not complete confidence in a given outcome; "at least some degree of predictability" is all that is required. M.P.E.P. § 2143.02.
The prior art can be modified or combined to reject claims as prima facie obvious as long as there is a reasonable expectation of success. See In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (see MPEP § 2143.02).
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Claims 1, 20-22 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over NCT03303989 (available 10/06/2017) as applied to claims 1 and 20-22 above.
The limitation of claims 1 and 20-22, as well as the corresponding teachings of NCT03303989, are described above and are hereby incorporated into the instant rejection.
The invention of claim 28 is similar to claim 1, however, claim 28 differs slightly from 1 in that claim 28 further requires anti-mPEG antibody levels prior to each dose of pegloticase.
NCT03303989 is not explicit in teaching the limitation of claim 28.
However, the invention of claim 28 would have been obvious over NCT03303989. This is because NCT03303989 discloses: i) that loss of response to pegloticase is associated with anti-pegloticase antibody formation (see page 2/11); and ii) measuring antibody levels among the secondary aims of the clinical trial (see page 3/11). Pegloticase is a mPEG linked uricase (see discussions above), therefore, anti-pegloticase antibody formation is necessarily anti-mPEG antibody formation.
Accordingly, at the time of the instant invention, a person skilled in the art would have found it obvious to measure anti-mPEG antibody levels in the patient before and after each dose of pegloticase, in order to assess the patient’s susceptibility to loss of response to pegloticase.
MPEP 2143(e) states: The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a). From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Thus, the claims fail to patentably distinguish over the state of the art as represented by the cited references.
Conclusions
No claim is allowable.
If Applicants should amend the claims, a complete and responsive reply will clearly identify where support can be found in the disclosure for each amendment. Applicants should point to the page and line numbers of the application corresponding to each amendment, and provide any statements that might help to identify support for the claimed invention (e.g., if the amendment is not supported in ipsis verbis, clarification on the record may be helpful). Should the Applicants present new claims, Applicants should clearly identify where support can be found in the disclosure.
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Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IBRAHIM D BORI whose telephone number is (571)270-7020. The examiner can normally be reached on Monday through Friday 8:00AM-5:00PM(EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY S LUNDGREN can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/IBRAHIM D BORI/
Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
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