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 .
DETAIED ACTION
Status of claims
Claims 314-333 are currently pending and under examination in the instant office action.
Information Disclosure Statement
A signed and initialed copy of the IDS papers filed on 9/26/2025 is enclosed in this action. The foreign non-patent literature documents lined through are not considered because Applicants did not provide their English translations.
Each information disclosure statement must further include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information listed that is not in the English language. The concise explanation may be either separate from the specification or part of the specification. If the concise explanation is part of the specification, the IDS listing should include the page(s) or line(s) numbers where the concise explanation is located in the specification.
The requirement for a concise explanation of relevance is limited to information that is not in the English language. The explanation required is limited to the relevance as understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information at the time the information is submitted to the Office. If a complete translation of the information into English is submitted with the non-English language information, no concise explanation is required. An English-language equivalent application may be submitted to fulfill this requirement if it is, in fact, a translation of a foreign language application being listed in an information disclosure statement. There is no requirement for the translation to be verified. Submission of an English language abstract of a reference may fulfill the requirement for a concise explanation. Where the information listed is not in the English language, but was cited in a search report or other action by a foreign patent office in a counterpart foreign application, the requirement for a concise explanation of relevance can be satisfied by submitting an English-language version of the search report or action which indicates the degree of relevance found by the foreign office. This may be an explanation of which portion of the reference is particularly relevant, to which claims it applies, or merely an “X”, “Y”, or “A” indication on a search report. The requirement for a concise explanation of non-English language information would not be satisfied by a statement that a reference was cited in the prosecution of a United States application which is not relied on under 35 U.S.C. 120.
Priority
This application is a continuation of the following US applications: 15/527252, 15/647036, 16/043641, 17/071740, 17/321788, 17/559557, 17/881227, 18/122483, 18/386460, 18/755487, and PCT/US15/60850. This application also claims priority to US provisional application Nos.: 62/080783, 62/140255, and 62/232963.
It is noted that the claimed prodrug of monoalkyl fumarate is not disclosed in US provisional applications: 62/080783 and 62/140255.
Also, claims 320 and 327 recite “the method further comprises informing the patient that PML has occurred in a MS patient who received a monoalkyl fumarate” or “therapy with a fumarate”. However, the original disclosure of the parent applications only discloses that PML has occurred in a patient who received dimethyl fumarate, not “MS patient”, not “monoalkyl fumarate” or not “therapy with a fumarate”. Thus, the patient can be any patient who received dimethyl fumarate (e.g., patient with psoriasis who was treated with dimethyl fumarate), not limiting to specific “MS patient” and the fumarate compound is limited to “dimethyl fumarate”, which is not a “monoalkyl fumarate”. Also, there is no disclosure or information regarding cases that PML has occurred in a MS patient in the original disclosure of the parent applications. Therefore, it is considered as new matter. New matter includes not only the addition of wholly unsupported subject matter, but may also include adding specific percentages or compounds after a broader original disclosure, or even the omission of a step from a method. See MPEP § 608.04 to § 608.04(c).
As such, the instant application should be identified as a continuation in part instead of continuation application since there is a new matter, which was not disclosed in the parent applications.
Accordingly, the instant claims are not entitled to the priority date of US provisional applications: 62/080783 and 62/140255 and claims 320 and 327 are not entitled to the priority date of any of the parent cases. The earliest effective U.S. filing date for the instant claims 314-319, 321-326, and 328-333 has been determined to be 9/25/2015, which is a filing date of the 62/232963 and that of claim 320 and 327 is 2/7/2025 which is the filing date of the instant application.
Objection to Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). As stated above, “the method further comprises informing the patient that PML has occurred in a MS patient who received a monoalkyl fumarate” in claims 320 and 327 is not disclosed in the remainder of the specification. See MPEP 2163.06 III.
Claim Rejections - 35 USC § 112 (b)
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 318, 322, and 324 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 pre-AIA the applicant regards as the invention.
Claims 318, 322, and 324 recite “the sign or symptom suggestive of PML”. However, claims 314, 316, and 317 in their dependency do not recite said “sign or symptom suggestive of PML”. Thus, there is insufficient antecedent basis for the limitation. Also, the full name of “PML should be provided.
Claim Rejections - 35 USC § 112(d)
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.
Claims 316-317 and 329-331 are 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.
The claims 316 and 329 are directed to administering “240 mg “monoalkyl fumarate” and claim 317 and 330 are directed to administering “120 mg “monoalkyl fumarate” for 7 days followed by 240 mg monoalkyl fumarate”. Also, claim 331 recites that fumarate therapy is of greater than 480 mg daily total monoalkyl fumarate. However, claims 314 and 325 from which they depend recite administering a prodrug of a “monoalkyl fumarate”, not a “monoalkyl fumarate”. Thus, they fail to further limit the subject matter of the claim upon which they depend, or to include all the limitations of the claim upon which they depend.
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 § 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.
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.
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 314-317, 325, and 328-331 are rejected under 35 U.S.C. 103 as being unpatentable over US 20150038499 (cited in the IDS filed on 9/26/2025) in view of TECFIDERA FDA Prescribing Information (March 27, 2013).
US 20150038499 teaches a method of treating a patient with multiple sclerosis comprising administering a pharmaceutical composition comprising monomethyl fumarate (MMF) and/or a prodrug of MMF such as 2-(2,5-dioxopyrrolidin-1-yl)ethyl methyl fumarate:
PNG
media_image1.png
94
229
media_image1.png
Greyscale
to the patient (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). Since monomethyl fumarate (MMF) or a prodrug of MMF is alternatively recited, the pharmaceutical composition encompasses a composition comprising the prodrug of MMF (monoalkyl fumarate) alone without a fumarate salt or additional fumarate other than the prodrug of MMF.
US 20150038499 further teaches that the methods are useful in increasing patient safety for patients considering treatment with MMF or a prodrug of MMF by appropriate patient screening and/or testing during MMF or MMF prodrug treatment and such compounds are known to cause a reduction in lymphocyte concentrations in certain patients, which can lead to an increased incidence rate of opportunistic infections such as multifocal leukoencephalopathy ([0062]). US 20150038499 further teaches that the compound is orally administered and a unit dosage form may be for a single daily dose, for administration 2 times per day, or one of multiple daily doses, e.g., 3 or more times per day ([0296] and [0299]).
Also, US 20150038499 teaches that the methods include suspending treatment to the patient(s) if the lymphocyte testing shows a lymphocyte blood concentration below about 1500 cells/µl (1.5x109/L) ([0013] and [0014]). In addition, US 20150038499 teaches that the term "lymphopenia" refers to the condition of having an abnormally low level of lymphocytes in the blood and typically refers to a count of less than 1,000 to 1,500 lymphocytes per microliter of blood in adults, or less than 3,000 lymphocytes per microliter of blood in children ([0044]). US 20150038499 further teaches that lymphocytes are white blood cells with important functions in the immune system and lymphocytes help protect the body from infection and low lymphocyte concentrations can raise the risk of infection ([0044]). US 20150038499 further teaches that the frequency of lymphocyte testing can be every 6 months, every 9 months or even longer and within the above-identified periods of lymphocyte testing frequencies, individual doctors may decide that the frequency of lymphocyte testing can and will vary ([0065] and [0066]).
Thus, the prior art teaches and suggests monitoring the counts of lymphocyte after 6 months of repeated administration and every 6 to 12 months thereafter. Furthermore, US 20150038499 discloses the followings: during the clinical testing of Tecfidera (dimethyl fumarate) for the treatment of multiple sclerosis, mean lymphocyte counts decreased in treated patients by approximately 30% during the first year of treatment with the drug, and then remained stable and four weeks after stopping Tecfidera, mean lymphocyte counts increased but did not return to baseline. Tecfidera also contains the following warnings in its prescribing information; (i) Tecfidera may cause lymphopenia; (ii) a recent complete blood count should be available before initiating treatment with Tecfidera; and (iii) a complete blood count is recommended annually, and as clinically indicated ([0007]).
US 20150038499 does not specifically teach interrupting administering of said pharmaceutical composition when the patient has lymphocyte count less than 0.5x 109/L persisting for more than six months.
According to TECFIDERA FDA Prescribing Information, TECFIDERA is indicated for the treatment of patients with relapsing forms of multiple sclerosis and is provided as hard gelatin delayed-release capsules for oral administration, containing 120 mg or 240 mg of dimethyl fumarate (DMF) (See 1 INDICATIONS AND USAGE and 11 DESCRIPTION). TECFIDERA therapy shows 49% (approximately 50%) reduction in proportion of patient relapses (See Table 2). It informs patients that TECFIDERA may decrease lymphocyte counts (see 17.4 Lymphocyte Counts). In addition, it discloses that 6% of the patients experienced lymphocyte counts <0.5 ×109/L, which is lower than the lower limit of normal 0.91×109/L (see 5.1 Lymphopenia). It further indicates that before initiating treatment with TECFIDERA, a recent CBC (i.e., within 6 months) should be available, a CBC is recommended annually, and as clinically indicated, and withholding treatment should be considered in patients with serious infections until the infection(s) is resolved (See the section of “Warning and Precaution” and Section 17.4). Furthermore, it discloses mean lymphocyte counts decreased by approximately 30% during the first year of treatment with TECFIDERA and then remained stable (See the section of “Warning and Precaution”).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to interrupt the treatment with the prodrug of MMF when the blood count including lymphocyte count is much lower than acceptable normal range because of the following reasons. US 20150038499 already teaches and suggest that the methods include suspending treatment to the patient(s) if the lymphocyte testing shows a lymphocyte blood concentration below 1.5x109/L, which encompasses less than 0.5 ×109/L. Also, it was known in the art that some patients treated with TECFIDERA experienced lymphocyte counts less than 0.5 ×109/L, which is lower than the lower limit of normal 0.91×109/L as evidenced by TECFIDERA FDA Prescribing Information. One of ordinary skill in the art would have recognized that having a lymphocyte count being less than 0.5 ×109/L for more than six months would indicate serious lymphopenia and a high risk of developing serious infection due to compromised immune functions as evidenced by US 20150038499. In addition, the skilled artisan would have recognized that the prodrug of MMF has the same pharmacologically active metabolite (i.e., MMF) as TECFIDERA (DMF) and is expected to have a similar efficacy/safety profile, including the effects on lymphocyte counts. Thus, the skilled artisan would have been motivated to interrupt the treatment with the prodrug of MMF for patients’ safety if the patient persistently has such abnormally low lymphocyte count as suggested by US 20150038499. In addition, the range of lymphocyte count disclosed in the prior art overlaps the claimed range. And in cases involving overlapping ranges, the courts have consistently held that even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Claims 320 and 326-327 are rejected under 35 U.S.C. 103 as being unpatentable over US 20150038499 (cited in the IDS filed on 9/26/2025) in view of TECFIDERA FDA Prescribing Information (March 27, 2013) in further view of Emrich et al. (“Tecfidera and PML- what is the story” Multiple sclerosis Net, April 25, 2013; cited in the IDS filed on 9/26/2025) and Zaheer et al. (Ther. Adv. Drug Saf. 2012, Vol. 3, No. 5: 227-239; cited in the IDS filed on 9/26/2025).
The teachings of US 20150038499 and TECFIDERA FDA Prescribing Information as applied supra are herein applied for the same teachings in their entirety.
The prior art does not specifically state “monitoring for a sign or symptom of PML” or “informing that PML has occurred in a MSpatient who received a fumarate and PML lead to death or severe disability over weeks or months”.
Emrich discloses that Tecfidera (oral dimethyl fumarate), also known as BG-12, has been approved by FDA for the treatment of relapsing forms of multiple sclerosis. However, skilled artisan has paid more attention on progressive multifocal leukoencephalopathy (PML) that may be associated with the administration of fumarate compounds. Multiple cases have been reported that patients taking a fumarate compound develop PML. It was suggested that treatment of fumaderm (mixture of dimethyl fumarate and monoethyl fumarate) or fumaric ester may have contributed to the development of severe and prolonged lymphopenia. It is further suggested that severe lymphopenia, which is a risk factor of PML, can be mitigated through periodic monitoring of lymphocytes. Emrich further reveals that in the MS placebo controlled trials of Tecfidera (dimethyl fumarate), Tecfidera is associated with a reduction in lymphocyte counts of approximately 30% during the first year of treatment and in trials, four weeks after stopping Tecfidera, mean lymphocyte counts increased but did not return to baseline. The FDA recommends that complete blood counts be checked before starting treatment and monitored thereafter. See, the entire document.
Zaheer et al. reveal that more PML associated with new developed therapeutic agents and PML is almost always associated with some underlying immunosuppression (abstract). Zaheer et al. teach that both multiple sclerosis (MS) and psoriasis have been known as diseases conditions for developing PML and while the detailed mechanism of therapy related PML has not been fully understood, the risk for PML must be considered for any therapy that alters immune function (abstract at page 227, left column of page 228, table 1 at page 229 and the conclusion section at page 235). In addition, Zaheer et al. discloses fumaric acid esters (FAEs) which are a group of related compounds as a therapeutic agent with risks of progressive multifocal leukoencephalopathy and several lines of evidence suggested immunomodulatory effects for FAEs. FAEs have been shown to reduce the number of T cells, particularly, CD4+ T cells, induce apoptosis of T cells (p234, right column, para 1). Zaheer et al. suggest that a high index of suspicion for PML needs to be maintained for individuals at risk to identify the disease as early as possible (see “Risk mitigation strategies”).
As to the recitation, “informing that PML has occurred in a patient who received a fumarate and PML lead to death or severe disability over weeks or months”, such information was already available before the effective filing date of the claimed invention as evidenced by Emrich. Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed the invention to provide known information and risk related to the fumarate therapy to a patient before the therapy because that is what a clinician normally and routinely does before initiating a treatment. In addition, it would have been prima facie obvious to monitor the sign or symptom of PML and to withhold the treatment when there is a sign or symptom of PML because Zaheer et al. suggest that a high index of suspicion for PML needs for identifying the risk of the disease as early as possible and FDA already recommended withholding treatment for patients with serious infections which encompasses PML.
Claims 318-319, 321-324, and 332-333 are rejected under 35 U.S.C. 103 as being unpatentable over US 20150038499 and TECFIDERA FDA Prescribing Information (March 27, 2013) in view of Emrich et al. (“Tecfidera and PML- what is the story” Multiple sclerosis Net, April 25, 2013, IDS) and Zaheer et al. (Ther. Adv. Drug Saf. 2012, Vol. 3, No. 5: 227-239), in further view of Berger (Cleveland Clinic Journal of Medicine, Vol. 78, supplement 2, S8-S12, 2011; cited in the IDS filed on 9/26/2025).
US 20150038499, TECFIDERA FDA Prescribing Information, Emrich et al., and Zaheer et al. as applied supra are herein applied for the same teachings in their entirety.
They do not specifically teach specific signs or symptoms of PML and performing an appropriate diagnostic evaluation of PML as recited in the claims. However, it was known in the art that the clinical signs or symptoms of PM include visual deficits, cognitive impairment, and motor weakness (hemiparesis, hemiplegia) and diagnosis is usually based on detection of JC virus in the cerebrospinal fluid by polymerase chain reaction, the clinical presentation, and demonstration of PML brain lesions on magnetic resonance imaging as evidenced by Berger (abstract). Thus, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed the invention to monitor known signs or symptoms of PML such as visual deficits, cognitive impairment, and motor weakness and to perform an appropriate diagnostic evaluation using known diagnostic technique for a patient showing such sign or symptom of PML as taught by Berger. That is what a clinician normally does for diagnosing a disease.
Double Patenting Rejection
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 obviousness-type 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); and 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 a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 314-333 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of US patent 11129806 in view of US 20150038499.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of treating a patient with multiple sclerosis comprising steps of: (a) administering a pharmaceutical composition comprising a fumarate such as dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination of dimethyl fumarate and monomethyl fumarate, to the patient with the provisos that: (i) a fumarate salt is not present in the pharmaceutical composition; and (ii) no additional fumarate other than the dimethyl fumarate, monomethyl fumarate, or combination thereof, is present in the pharmaceutical composition; (b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; and (c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5 x 109/L persisting for more than six months.
The claims of the patent do not recite the claimed prodrug of monoalkyl fumarate. However, US 20150038499 discloses the claimed compound as a prodrug of monoalkyl fumarate (MMF) and teaches the use of MMF and the prodrug of MMF for treating multiple sclerosis as claimed (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). Thus, it would have been prima facie obvious to use the prodrug of MMF in place of dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination thereof because the prodrug of MMF would be transformed into MMF in vivo and thus one of ordinary skill in the art would reasonably expected that the prodrug of MMF would have the same effects as its active metabolite, MMF. As such, the claims of the instant application would have been obvious over those of the patent.
Claims 314-333 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-19 of US patent 10959972 in view of US 20150038499.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of treating a patient with multiple sclerosis comprising steps of: (a) administering a pharmaceutical composition comprising dimethyl fumarate (DMF) to the patient with the provisos that: (i) a fumarate salt is not present in the pharmaceutical composition; and (ii) no additional fumarate other than the dimethyl fumarate is present in the pharmaceutical composition; (b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; (c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5 x 109/L persisting for more than six months; and (d) monitoring the patient for a sign or symptom suggestive of progressive multifocal leukoencephalopathy (PML) in the patient.
The claims of the patent do not recite the claimed prodrug of monoalkyl fumarate. However, US 20150038499 discloses the claimed compound as a prodrug of monoalkyl fumarate (MMF) and teaches the use of MMF and the prodrug of MMF for treating multiple sclerosis as claimed (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). It would have been prima facie obvious to use the prodrug of MMF in place of dimethyl fumarate (DMF) because the prodrug of MMF and DMF would be transformed into MMF in vivo and thus one of ordinary skill in the art would reasonably expected that the prodrug of MMF would have the same effects as DMF. As such, the claims of the instant application would have been obvious over those of the patent.
Claims 314-333 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-22 of US patent 11007167 in view of US 20150038499.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of treating a patient with multiple sclerosis comprising steps of: (a) administering a pharmaceutical composition comprising a fumarate such as dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination of dimethyl fumarate and monomethyl fumarate comprising dimethyl fumarate (DMF) to the patient with the provisos that: (i) a fumarate salt is not present in the pharmaceutical composition; and (ii) no additional fumarate other than the dimethyl fumarate is present in the pharmaceutical composition; (b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; (c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5 x 109/L persisting for more than six months; and (d) monitoring the patient for a sign or symptom suggestive of progressive multifocal leukoencephalopathy (PML) in the patient.
The claims of the patent do not recite the claimed prodrug of monoalkyl fumarate. However, US 20150038499 discloses the claimed compound as a prodrug of monoalkyl fumarate (MMF) and teaches the use of MMF and the prodrug of MMF for treating multiple sclerosis as claimed (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). Thus, it would have been prima facie obvious to use the prodrug of MMF in place of dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination thereof because the prodrug of MMF would be transformed into MMF in vivo and thus one of ordinary skill in the art would reasonably expected that the prodrug of MMF would have the same effects as its active metabolite, MMF. As such, the claims of the instant application would have been obvious over those of the patent.
Claims 314-333 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-16 of US patent 11007166 in view of US 20150038499.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of treating a patient with multiple sclerosis comprising steps of: administering a pharmaceutical composition comprising 240 mg dimethyl fumarate (DMF) twice a day to the patient with the provisos that: (i) a fumarate salt is not present in the pharmaceutical composition; and (ii) no additional fumarate other than the dimethyl fumarate is present in the pharmaceutical composition, wherein the patient has had at least one lymphocyte count below 0.5 x 109/L obtaining a complete blood count and has not had lymphocyte count below 0.5 x 109/L that persists for more than 6 months, further comprising monitoring the patient for a sign or symptom suggestive of progressive multifocal leukoencephalopathy (PML) in the patient.
The claims of the patent do not recite the claimed prodrug of monoalkyl fumarate. However, US 20150038499 discloses the claimed compound as a prodrug of monoalkyl fumarate (MMF) and teaches the use of MMF and the prodrug of MMF for treating multiple sclerosis as claimed (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). Thus, it would have been prima facie obvious to use the prodrug of MMF in place of dimethyl fumarate (DMF) because the prodrug of MMF and DMF would be transformed into MMF in vivo and thus one of ordinary skill in the art would reasonably expected that the prodrug of MMF would have the same effects as DMF. As such, the claims of the instant application would have been obvious over those of the patent.
Claims 314-333 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of US patent 11129806 in view of US 20150038499.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of treating a patient with multiple sclerosis comprising steps of: (a) administering a pharmaceutical composition comprising a fumarate such as dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination of dimethyl fumarate and monomethyl fumarate, to the patient with the provisos that: (i) a fumarate salt is not present in the pharmaceutical composition; and (ii) no additional fumarate other than the dimethyl fumarate, monomethyl fumarate, or combination thereof, is present in the pharmaceutical composition; (b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said pharmaceutical composition to said patient, and every 6 to 12 months thereafter; and (c) interrupting administering of said pharmaceutical composition to said patient when the patient has a lymphocyte count less than 0.5 x 109/L persisting for more than six months.
The claims of the patent do not recite the claimed prodrug of monoalkyl fumarate. However, US 20150038499 discloses the claimed compound as a prodrug of monoalkyl fumarate (MMF) and teaches the use of MMF and the prodrug of MMF for treating multiple sclerosis as claimed (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). Thus, it would have been prima facie obvious to use the prodrug of MMF in place of dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination thereof because the prodrug of MMF would be transformed into MMF in vivo and thus one of ordinary skill in the art would reasonably expected that the prodrug of MMF would have the same effects as its active metabolite, MMF. As such, the claims of the instant application would have been obvious over those of the patent.
Claims 314-333 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-27 of US patent 11246850 in view of US 20150038499 .
Although the conflicting claims are not identical, they are not patentably distinct from each other because the claims of the patent are drawn to a method of treating multiple sclerosis comprising: (a) administering furmarate therapy to a population of MS patients comprising a subpopulation of patients that experience a lymphocyte count of less than 0.5×10.sup.9/L while receiving such fumarate therapy, wherein said fumarate therapy is treatment with dimethyl fumarate (DMF) and/or monoethyl fumarate; (b) obtaining a complete blood count including lymphocyte count after 6 months of repeated administering of said fumarate therapy and every 6 to 12 months thereafter; (c) interrupting administering of said fumarate therapy to said subpopulation when the lymphocyte count less than 0.5 x 109/L persists for more than six months; and (d) monitoring the patient for a sign or symptom suggestive of progressive multifocal leukoencephalopathy (PML) in the patient.
The claims of the patent do not recite the claimed prodrug of monoalkyl fumarate. However, US 20150038499 discloses the claimed compound as a prodrug of monoalkyl fumarate (MMF) and teaches the use of MMF and the prodrug of MMF for treating multiple sclerosis as claimed (abstract, [0002], [0047], [0081], [0285], and claims 1 and 20). Thus, it would have been prima facie obvious to use the prodrug of MMF in place of dimethyl fumarate (DMF) or monomethyl fumarate (MMF) because the prodrug of MMF would be transformed into MMF in vivo and thus one of ordinary skill in the art would reasonably expected that the prodrug of MMF would have the same effects as its active metabolite, MMF. As such, the claims of the instant application would have been obvious over those of the patent.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BONG-SOOK BAEK whose telephone number is 571-270-5863. The examiner can normally be reached 9:00AM-6:00PM Monday-Friday.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bethany Barham can be reached on 571-272-6175. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611
