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 .
Priority
This application is a national stage application under 35 U.S.C. § 371 of International Application No. PCT/CN2022/100198, filed 06/21/2022, which claims the priority benefit of CHINA Application No. 202110688144.0, filed 06/21/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/11/2023, and 06/16/2025 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of the Application
Claims 1, and 4-19 are pending and currently under examination. Claims 2-3 been cancelled by applicant without prejudice or disclaimer.
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 7 and 11 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.
The term “Site(s)” in claim 7, lines 2, 3 and 5 is a relative term which renders the claim indefinite. The term “Site(s)” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
This rejection may be overcome by clearly defining what constitutes a “site” as it pertains to claim 7.
Claim 7 is 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 7 depends from claim 1 and recites “wherein for the mild chronic graft vs host disease…”. However, claim 1 does not introduce a mild chronic graft vs host disease. There is no mention of the severity types (mild, moderate, severe) chronic graft-versus-host disease in independent claim 1, from which claim 7 depends. This rejection may be overcome by amending the dependency of claim 7 from independent claim 1 to dependency on dependent claim 6. It is also noted that Claim 7 recites the values of score, ranging from <1 to 3, that do not correlate to the mild, moderate, severe GVHD rating given in the instant claim. Examiner suggests amending the claim to clearly indicate how the relationship of number of organs and scores are related in regards to the severity of GVHD.
Regarding claim 11, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 11 recites the broad recitation “1 mg to 50 mg”, and the claim also recites “preferably 5 mg to 30 mg, 5 mg to 25 mg, 5 mg to 20 mg, and 10 mg to 20 mg” which is the narrower statement of the range/limitation. The claim are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
This rejection may be overcome by amending the claim to clearly indicate what the daily dose of formula I is.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 4, 8-9, 11-19 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zeiser (Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease).
Zeiser discloses “phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator’s choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28.The key secondary end point was durable overall response at day 56.” (pg. 1800, methods)
Zeiser’s ruxolitinib satisfies the structural limitations of applicants formula I of the instant claims and further more Zeiser’s method of administering ruxolitinib (applicant’s formula I) in a 10 mg dose twice a day for 28 days followed by a consecutive second 28 day period to treat glucocorticoid-refractory acute graft-versus-host disease (GVHD) after allogeneic stem-cell transplantation anticipate the instant claims where a dose of 10 mg formula I is administered twice daily in 28 day cycles (560 mg per cycle) to treat GVHD which is caused by allogeneic stem cell transplantation and, is glucocorticoid-refractory. See also MPEP 2131.03.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 4-19 are rejected under 35 U.S.C. 103 as being unpatentable over Zeiser (Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease) in view of Xue (Ruxolitinib for chronic steroid-refractory graft versus host disease: a single center experience).
The instant claims are directed to a method of treating graft-versus-host disease (GVHD) in a patient by administering the compound of formula I in a daily dose range of 1-50 mg in a 28 day cycle wherein the GVHD is glucocorticoid refractory and/or dependent and includes classical and acute chronic overlap syndrome ranging in severity from mild to severe base on the number of organs affected.
Zeiser et al. teach “phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator’s choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28.The key secondary end point was durable overall response at day 56.” (pg. 1800, methods). Zeiser also teaches glucocorticoid taper in which an increase in the methylprednisolone dose to >2 mg per kilogram of body weight per day [or equivalent >2.5 mg per kilogram per day of prednisone] or an inability to taper the dose to <0.5 mg per kilogram per day of methylprednisolone [or equivalent <0.6 mg per kilogram per day of prednisone] for a minimum of 7 days) (pg. 1801, patients section). Zeiser discloses a therapy for acute and chronic GVHD (pg. 1802, 2nd para., endpoints and assessments section). Zeiser also discloses the Food and Drug Administration (FDA) approved ruxolitinib for use in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD (pg. 1807, discussion, 2nd para.).
However, Zeiser et al. fail to disclose GVHD acute and chronic overlap syndrome or specify mild, moderate and severe chronic graft-versus-host diseases.
Xue et al. teach patients were treated for GvHD according to institutional guidelines wherein first line treatment is prednisone at 1 mg/kg (pg. 2, section 2.1). Xue also teaches (pg. 2, introduction). Xue discloses treatment of chronic GVHD overlap with ruxolitinib as” Overall, 15 patients presented overlap features. Both overlap and progressive features point out for a worst prognosis of chronic GvHD. At time of ruxolitinib start, chronic GvHD was scored as moderate and severe in 9 (25 %) and 27 (75 %) cases, respectively, and thirty-three patients were receiving steroid. Cutaneous GvHD was the most common presentation (30/36, 83 %) and also the organ that showed most frequently the highest severity score (NIH 2014 score severe: 18/36, 50 %).” (pg. 3, section 3.1)
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to administer a method of treating GVHD in a patient by administering the compound of formula I (ruxolitinib) in a daily dose range of 1-50 mg in a 28 day cycle wherein the GVHD is glucocorticoid refractory and/or dependent chronic or dependent GVHD as disclosed by Zeiser and look towards Xue’s disclosure of ruxolitinib in treating GVHD including classical and acute chronic overlap syndrome ranging in severity from mild to severe base on the number of organs affected.
A person of ordinary skill in the art would have been motivated to combine Zeiser’s teachings of methylprednisolone, prednisone and administering ruxolitinib in a twice daily 10 mg dose for the treatment of glucocorticoid-refractory acute GVHD including after allogeneic stem-cell transplantation with Xue’s disclosure of treating patients displaying overlap features of GVHD based on the (National Institutes of Health (NIH) 2014 score system) because a skilled artisan would have recognized it as obvious to try when ruxolitinib was already FDA approved ruxolitinib for use in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD and would have therefore had a reasonable expectation of success in also treating classical and acute chronic overlap syndrome ranging in severity from mild to severe based on the number of organs affected by combining Zeiser and Xue’s methods of treating GVHD. See MPEP 2131.03, 2144.05(II), and 2144.06-07.
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 and 4-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,447,154. Although the claims at issue are not identical, they are not patentably distinct from each other because it would have been prima facie obvious to a person having ordinary skill following the patented claims to perform the method on a patient having graft vs host disease with hemophagocytic syndrome with a reasonable expectation of treatment.
Conclusion/Correspondence
All claims are rejected, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C Milligan can be reached at 571-270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
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