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
Election/Restriction
Applicant’s election without traverse : 1) Group I invention (claims 1-16, 27, and 29-31), drawn to a method of treating a patient with globoid cell leukodystrophy or Krabbe disease, comprising administration to a patient in need thereof an effective amount of a pharmaceutical composition comprising gemfibrozil and at least one pharmaceutically acceptable excipient or carrier ; 2) method species for inhibiting progression of the globoid cell leukodystrophy or Krabbe disease, in the reply filed on 12/04/2025 is acknowledged.
Claims 17-26 and 28, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
After searching prior art and further consideration, the elected method treatment species “inhibiting progression of the globoid cell leukodystrophy or Krabbe disease” recited in claims 3, 6, 9 and 12 are considered as associated with other intended treatment outcome of administering gemfibrozil as recited in claims 1, 4, 7, 10, respectively. As such, requirement of species elections regarding the intended treatment outcome are withdrawn.
Status of Claims
Claims 1-31 are pending in the instant application.
Claims 17-26 and 28 are withdrawn.
Claims 1-16, 27, and 29-31 are currently under examination.
Priority
The instant application 18/261, 959 filed on 07/18/2023 is 371 of PCT/US2021/014124 filed on 01/20/2021.
Information Disclosure Statement
The information disclosure statements filed 03/27/2025 and 07/18/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the reference listed in IDS are being considered by the Examiner.
Claim Objections
Claims 1, 3-7, 9-10, 12, 13, 14 and 30 are objected to because of following informalities:
Claim 1 recites a method for protecting the degeneration of myelin in the nervous system of a patient with globoid cell leukodystrophy or Krabbe disease, comprising the administration to a patient in need thereof an effective amount of a pharmaceutical composition comprising gemfibrozil and at least one pharmaceutically acceptable excipient or carrier. There is no antecedent basis for the degeneration of myelin and the administration.
The definite article “the” are redundant and not necessary in some limitation of instant claims. For example, independent claims 1, 4, 7, 10, 13 recite “ the administration to a patient in need thereof”, claims 3, 6, 9, 12, 14 recite “the progression of the globoid cell leukodystrophy or Krabbe disease”.
Claim 5 recites “ the method of claim 5”.
Claim 30 recites “wherein the oral solid dosage is one or more of oral, buccal or sub-lingual”. The second oral is redundant and not further limiting the oral solid dosage form. The sub-lingual should be followed by “dosage form”.
Claim Interpretation
Independent claims are directed to a method of treating or inhibiting progression of globoid cell leukodystrophy or Krabbe disease, comprising administration to a patient in need thereof an effective amount of a pharmaceutical composition comprising gemfibrozil and at least one pharmaceutically acceptable excipient or carrier. Regarding the limitation of intended treatment outcome recited in instant claims, e.g. “protecting the degeneration of myelin in the nervous system”(claim 1), “ inhibits the progression of the globoid cell leukodystrophy or Krabbe disease” recited in claims 3, 6, 9, 12, and 14, “improving the locomotor activity of a patient with globoid cell leukodystrophy or Krabbe disease” (claim 7) , “increasing the lifespan of a patient with globoid cell leukodystrophy or Krabbe disease” (claim 10), etc. these recitations are construed as intended results of active method step of administering an effective amount of a pharmaceutical composition comprising gemfibrozil and pharmaceutical acceptable carrier to a patient in need thereof ( e.g. globoid cell leukodystrophy or Krabbe disease), which do not materially limit the claimed method since such limitations do not result in manipulative difference in method steps of the claims. Please note the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. “[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer.” Atlas Powder Co. v. Ireco Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir.1999). If the prior art teaches and/or suggests the same or similar method step as instantly claimed (i.e. administering an effective amount of a pharmaceutical composition comprising gemfibrozil to a patient with globoid cell leukodystrophy or Krabbe disease), the method of the prior art would have achieved the intended results recited in instant claims and read on instant claimed methods. The burden of proof is shifted to the Applicant to show that the subject matter of the prior art does not possess the characteristic relied on whether the rejection is based on inherency under 35 U.S.C.102 or obviousness under 35 U.S.C. 103.
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 3, 6, 9, 12 and 14 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.
Dependent claims 3, 6, 9, 12 and 14 reciting intended treatment outcome, “wherein the administration of the pharmaceutical composition inhibits the progression of the globoid cell leukodystrophy or Krabbe disease” are indefinite because they merely define the invention in terms of results to be achieved and do not provide any clear further restraints on the method steps of administrating an effective amount of a pharmaceutical composition comprising gemfibrozil and at least one pharmaceutically acceptable excipient or carrier to a patient in need thereof. One of ordinary skill in the art cannot determine the metes and bounds of these claims because it is unknown how the treatment outcome is further limiting to instant claimed methods.
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.
Claim 12 is 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.
Claim 12 depends on claim 9, both claims 9 and 12 recite “wherein the administration of the pharmaceutical composition inhibits the progression of the globoid cell leukodystrophy or Krabbe disease”. Claim 12 fails to further limit the subject matter of claim 9. 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 § 102/103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 4, 6, 7, 9, 10, 12-16, 27, and 29-30 are rejected under 35 U.S.C. 102 (a)(2) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lee (WO 2021/167860 A1, Applicant’s IDS dated 03/27/2025).
Lee teaches a method of treating a subject having Krabbe disease comprising administering a pharmaceutical composition comprising gemfibrozil salt and pharmaceutically acceptable carrier/excipient (See abstract, [0009], [0194], claim 20)(which reads on claim 13 and 16).
Lee teaches gemfibrozil treating neuronal lysosomal storage disease (e.g. Krabbe disease) associated with abnormal accumulations of lipofuscins within cells of the CNS that may involve peroxisome proliferator activated receptor (PPAR) and gemfibrozil may provide overall enhanced lysosomal biogenesis resulting in decreased accumulations of lipofuscins within cells of the CNS (See [0002] ). Lee also teaches a method of treating a subject having other neurogenerative disease, e.g. Tay Sachs disease, Sandoff disease, Fabry disease, Krabbe disease, Niemann-Pick disease, Gaucher disease, Hunter Syndrome, Alpha-mannosidosis, Aspartylglucosaminuria, Cholesteryl ester storage disease, Chronic Hexosaminidase A Deficiency, Cystinosis, Danon disease, Farber disease, Fucosidosis, and Galactosialidosis and Neuronal Ceroid Lipofuscinoses (See [0194], claim 20).
Lee teaches pharmaceutical composition comprising gemfibrozil salt and further comprises at least one of a pharmaceutically acceptable carrier or a pharmaceutically acceptable excipient (See [0137]-[0138]).
Regarding the administration limitation, Lee teaches gemfibrozil salt may be administered once daily, twice daily or three times daily (See [0144]) (which reads on instant claims 15, 27).
Regarding the dosage form of instant claims 29-31, Lee teaches gemfibrozil composition in an form of oral formulation (See [0137], claim 19) that could be administered through buccal, sublingual, or a transmucosal route(See [0140], [0195], claim 21) (which reads on instant claim 30).
Lee collectively teaches the same method step as instantly claimed (i.e., administering a pharmaceutical composition comprising gemfibrozil salt and carrier to a subject having Krabbe disease), thus, Lee anticipates instant claimed method of treating Krabbe disease with gemfibrozil.
Lee is silent about intended treatment outcome/result as recited in independent claims 1, 4, 7 and 10. As elaborate in the Claim Interpretation section, the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. The intended treatment outcome would inevitably flow from Lee’s teaching since the same compound (e. g. gemfibrozil) is being administered to the subjects in need thereof (i.e. a subject having Krabbe disease). It’s noted there are no dosage regimen or specific administration limitation recited in instant claims that are different from Lee. As such, Lee’s method of treating Krabbe disease would have achieved the intended results recited in instant claims if instant claimed gemfibrozil composition functions as recited.
In the alternative, even if instantly claimed treatment outcome/result is slight different from Lee’s method of treating a subject having Krabbe disease, the differences between what is disclosed in prior art and what is claimed are considered to be slight that the method taught by Lee is likely to possess the similar effects of instantly claimed method in view of the similar characteristics which they have been shown to share. It’s noted there are no dosage regimen or specific administration limitation recited in instant claims that are different from Lee. Thus, the instant claimed methods would have been obvious to those of ordinary skill in the art within the meaning of USC 103. Accordingly, the claimed invention as a whole was at least prima facie obvious, if not anticipated by the cited reference, especially in the absence of sufficient, clear, and convincing evidence to the contrary. The burden of proof is shifted to the Applicant to show that the subject matter of the prior art does not possess the characteristic relied on whether the rejection is based on inherency under 35 U.S.C.102 or obviousness under 35 U.S.C. 103.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
Claims 1-16, 27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Pahan ( US20170354666A1, hereafter “Pahan’ 666”, Applicant’s IDS dated 03/27/2025), in view of Jana et al. ( The Journal of Biological Chemistry, 2012, Aug 9;287(41):34134–34148. doi: 10.1074/jbc.M112.398552, “Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β”) and Ghosh et al. (J. Neurochem, 2017, May;141(3):423-435, hereafter “ Ghosh’ 2017”, doi: 10.1111/jnc.13987. Epub 2017 Apr 3, “Gemfibrozil, food and drug administration-approved lipid-lowering drug, increases longevity in mouse model of late infantile neuronal ceroid lipofuscinosis”).
Pahan’ 666 teaches a method for treatment of a lysosomal storage disorder, comprising administering to a subject in need thereof a therapeutically effective amount of composition comprising an active agent upregulation of Transcription Factor EB, e.g. lipid-lowering drug, fibrate/ gemfibrozil and vitamin A (See abstract, [0007], claims 1, 5-14, 27, 31-35).
Pahan’ 666 teaches embodiments wherein the composition further comprises a therapeutically effective amount of all-trans retinoic acid or vitamin A (See [0008], [0036]-[0037], claim 8).
Pahan’ 666 teaches embodiment wherein the composition comprises the fibrate (e.g. gemfibrozil) and all-trans retinoic acid/ vitamin A upregulating TFEB mRNA and protein levels in brain cells and other assays (See [0012]-[0019], [0041], claim 9-10, Fig 1-8.). Pahan’ 666 teaches combination of gemfibrozil fibrate and vitamin A may be a synergistic providing greater therapeutic effect in the subject than administration of vitamin A or the fibrate alone (See [0008]).
Pahan’ 666 teaches lysosomal storage disorder (LSDs) are a group of inherited metabolic disorders that result from defects in lysosomal function and exemplary neurodegenerative disorder selected from Tay-Sach's disease, Fabry disease, Niemann-Pick disease, Gaucher disease, Hunter Syndrome, Alpha-mannosidosis, Aspartylglucosaminuria, Cholesteryl ester storage disease, Chronic Hexosaminidase A Deficiency, Cystinosis, Danon disease, Farber disease, Fucosidosis, and Galactosialidosis (See [0005], [0010], claims 11 and 35).
Regarding the pharmaceutical composition, Pahan’ 666 explicitly teaches pharmaceutical composition comprising gemfibrozil and vitamin A (See 0041]).
Regarding the administration limitation, Pahan’ 666 teaches gemfibrozil or a combination thereof may be administered in a single daily dose or in multiple doses per day (See [0044]-[0045]) (which reads on instant claims 15, 27).
Regarding the dosage form of instant claims 29 and 31, Pahan’ 666 teaches pharmaceutical composition comprising active agent and commonly known excipients in the form of tablets, pills, aqueous or oily suspensions, syrups, alixiers, solid emulsions, solid dispersions, etc. (See [0042]-[0043])
Regarding claim 30, Pahan’ 666 teaches variety of administration route, e.g. oral, parenteral, etc.
Pahan’ 666 collectively teaches method of treating variety of lysosomal storage disease with a pharmaceutical composition comprising gemfibrozil alone or in combination with vitamin A and pharmaceutical excipient/carrier, wherein combination of gemfibrozil and vitamin A may be synergistic for treating lysosomal storage disease.
Pahan’ 666 is silent about Krabbe disease is lysosomal storage disorder and intended treatment outcome/result. As elaborate in the Claim Interpretation section, the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances.
Further, Jana teaches gemfibrozil treatment restores the recruitment of PPAR-B to the mouse PLP promoter, inhibits demyelination in spinal cord, and suppresses EAE in PLP-TCR transgenic mice(See whole article, abstract, Fig 1). Jana collectively teaches a novel myelinogenic property of gemfibrozil and gemfibrozil may be of therapeutic benefit in MS and other demyelinating diseases (which reads on instant claim 1).
Ghosh 2017 teaches oral administration of gemfibrozil upregulates the expression of anti-inflammatory molecules like interleukin-1 receptor antagonist (IL-1Ra) and suppressor of cytokine
signaling 3 (SOCS3) in vivo in the brain of Cln2 null mice, an animal model of late infantile neuronal ceroid lipofuscinosis, leading to the suppression of neuronal apoptosis, increased survival and improved locomotor activity (See whole article, Graphical abstract; Results) (which reads on instant claims 4, 7 and 10). Ghosh 2017 and its incorporated reference teach the mechanism of gemfibrozil treatment, e.g. prolongs the lifespan in Cln2(−/−) mice, improves motor behavior, lowers the burden of storage material in the brain and other benefit (See Results, page 5 to 8; Discussion) Neuronal apoptosis is a hallmark of most of the known neurodegenerative diseases including lysosomal storage disorders. Strong inhibition of neuronal apoptosis in different parts of the CNS of Cln2 (−/−) mice by gemfibrozil suggests that this anti-apoptotic property of gem may contribute to its lifespan-prolonging efficacy (See Discussion, page 8).
It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound as demonstrated in Pahan’ 666 treating variety of lysosomal disease with gemfibrozil alone or in combination with vitamin A. A skilled artisan would have known Krabbe disease is lysosomal storage disorder that belong to the same group of disease taught by Pahan’ 666. It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to further explore gemfibrozil alone or in combination with vitamin A for treating other lysosomal storage disease (e.g. Krabbe disease), based on combined beneficial teachings of prior art and general knowledge of treating neurological disorder (e.g. lysosomal storage disease) and arrived instantly claimed invention with reasonable expectation of success. A skilled artisan would be motivated to explore gemfibrozil alone or in combination with vitamin A for treating Krabbe disease because Krabbe disease is a lysosomal storage disorder associated with lysosomal function as other lysosomal disease (e.g. Tay-Sach's disease, etc.).
Regarding instantly claimed treatment outcome/ intended result, As elaborate in the Claim Interpretation section, the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. A skilled artisan would reasonably expect gemfibrozil alone or in combination with vitamin A administered to a subject with Krabbe disease might provide an alternative treatment for Krabbe disease based on the neuroprotective properties of gemfibrozil taught by prior art with instant claimed treatment outcome which is the property/biological activity of gemfibrozil.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization of for intended treatment outcome based on the general knowledge of treating neurological disorder (e.g. lysosomal storage disease, Krabbe disease). Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-16, 27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Lee (WO 2021/167860 A1, Applicant’s IDS dated 03/27/2025) in view of Pahan ( US20170354666A1, “Pahan’ 666”, Applicant’s IDS dated 03/27/2025).
The collective teachings of Lee and Pahan’ 666 are elaborated in preceding 103 rejections and applied as before.
Lee teaches a method of treating a subject having Krabbe disease comprising administering a pharmaceutical composition comprising gemfibrozil salt and pharmaceutically acceptable carrier/excipient.
Lee is silent about vitamin A in combination with gemfibrozil.
Pahan’ 666 teaches combination of gemfibrozil and vitamin A may be a synergistic providing greater therapeutic effect in the subject than administration of vitamin A or the fibrate alone for treating lysosomal storage disorder.
It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to explore gemfibrozil in combination with vitamin A for treating Krabbe disease as taught by Lee, and arrived instantly claimed invention with reasonable expectation of success. A skilled artisan would be motivated to combine the teachings of Lee and Pahan’666 because both teachings are directed to gemfibrozil for treating lysosomal storage disease.
Regarding instantly claimed treatment outcome/ intended result, the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. A skilled artisan would reasonably expect gemfibrozil in combination with vitamin A administered to a subject with Krabbe disease might provide an treatment for Krabbe disease with instant claimed treatment outcome which is the property/biological activity of gemfibrozil.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization of for intended treatment outcome based on the general knowledge of treating neurological disorder (e.g. lysosomal disease, Krabbe disease). Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 4, 6-7, 9-10, 12-16, 27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Pahan (WO 2018126000A1 , hereafter “Pahan’ 000”, patent family of US20190358188A1/ US11020366B2).
Pahan’ 000 teaches a method for treatment of a neurodegenerative disease comprising administering to the subject a composition comprising a therapeutically effective amount of fibrate (e.g. gemfibrozil) (See abstract, [0005]-[0006], claims 1-22).
Pahan’ 000 teaches therapeutic efficacy of gemfibrozil in mouse model of LINCL wherein behavioral analysis and survival studies on Clnl2 mice showed increased longevity and improvement of motor behavior in gem-treated animals compared to vehicle (0.1% methyl cellulose)-treated controls. “The burden of storage materials and neuronal apoptosis were also found to be partially reduced in gem-treated animals with increase in levels of phospho- BCL2 Associated Agonist Of Cell Death (P-BAD), an anti-apoptotic molecule. Furthermore, levels of anti-inflammatory factors like suppressor of cytokine signaling 3 (SOCS3) and Interleukin-1 receptor antagonist (IL-IRa) was found to be elevated in gem- treated animals. Taken together, this study indicates a neuroprotective role of gemfibrozil”( See [0005]).
Regarding instant claims 4 and 6, Pahan’ 000 teaches a method of increasing levels of anti-inflammatory factors in a brain of a subject having neurodegenerative disease (e.g. late infantile neuronal ceroid lipofuscinosis) comprising administering to the subject a composition comprising a therapeutically effective amount of fibrate (e.g. gemfibrozil( See [0005], claims 18-21). Pahan’ 000 teaches increase in the levels of anti-inflammatory factors comprises an increase in the level of suppressor of cytokine signaling 3 (SOCS3) and Interleukin-1 receptor antagonist (IL-IRa) (See claim 21).
Regarding instant claims 7 and 9, Pahan’ 000 teaches a method of improving motor behavior of a subject having a neurodegenerative disease comprising administering to the subject a composition comprising a therapeutically effective amount of fibrate (e.g. gemfibrozil) (See [0010], [0013]-0015] claim 7)
Regarding instant claims 10 and 12, Pahan’ 000 teaches a method of prolonging a lifespan of a subject having a neurodegenerative disease comprising administering to the subject a composition comprising a therapeutically effective amount of fibrate (e.g. gemfibrozil) (See [0009], [0051], Example 2, claim 8-10). Pahan’ 000 also teaches a method of decreasing neuronal apototic cell death in a subject having neurodegenerative disease (e.g. neuronal ceroid lipofuscinosis, Alzheimer's disease, etc.) (See claim 1).
Regarding instant claim 15 and 27, Pahan’ 000 teaches subject were treated daily with gemfibrozil (7.5 mg/kg body weight/day) (See [0051]).
Regarding claims 29-31, Pahan’ 000 teaches pharmaceutical composition in various forms, e.g. suspensions, solid emulsions, solid dispersions, etc. (See 0037]. Pahan’ 000 teaches the agent is for oral or parenteral administration (See Example 1- 6, claim 22). Pahan’ 000 also teaches "oral" refers to modes of administration which include oral, enteral, buccal, sublabial, sublingual, etc..
Pahan’ 000 teaches variety of neurodegenerative disease, e.g. neuronal ceroid lipofuscinosis, Alzheimer's disease, Huntington's disease, Amyotrophic lateral sclerosis (ALS), Parkinson's disease, including Parkinson's plus diseases such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) or dementia with Lewy bodies (DLB)…The neurodegenerative disease may be caused by a lysosomal storage disorder, for example, Tay-Sach's disease, Fabry disease, Niemann-Pick disease, Gaucher disease, Hunter Syndrome, Alpha-mannosidosis, Aspartylglucosaminuria, Cholesteryl ester storage disease, Chronic Hexosaminidase A Deficiency, Cystinosis, Danon disease, Farber disease, Fucosidosis, or Galactosialidosis (See [0006])
Pahan’ 000 teaches a method for treatment of a neurodegenerative disease comprising administering to the subject a composition comprising a therapeutically effective amount of gemfibrozil wherein the intended treatment outcome, e.g. of prolonging a lifespan, improving motor behavior in the subject, read on instant intended treatment outcome.
Pahan’ 000 is silent about treating Krabbe disease and intended treatment outcome.
It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound. It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to further explore gemfibrozil for treating other neurodegenerative disease (e.g. Krabbe disease), based on combined teachings of prior art and general knowledge of neurological disorder and arrived instantly claimed invention with reasonable expectation of success. A skilled artisan would be motivated to explore gemfibrozil for treating other neurodegenerative disease (e.g. Krabbe disease) since Krabbe disease is lysosomal storage disease that belongs to the same group of neurological disorder as taught by Pahan’ 000.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization of for intended treatment outcome based on the general knowledge of treating neurological disorder (e.g. lysosomal disease, Krabbe disease). Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1-16, 27, and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Pahan ( WO 2018126000A1 , “Pahan’ 000”), in view of Pahan ( US20170354666A1, “Pahan’ 666”, Applicant’s IDS dated 03/27/2025), and Jana et al. ( The Journal of Biological Chemistry, 2012, Aug 9;287(41):34134–34148. doi: 10.1074/jbc.M112.398552, “Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β”).
The collective teachings of Pahan’ 000, Pahan’ 666 and Jana are elaborated in preceding 103 rejections and applied as before.
Pahan’ 000 teaches a method for treatment of a neurodegenerative disease comprising administering to the subject a composition comprising a therapeutically effective amount of gemfibrozil wherein the intended treatment outcome, e.g. of prolonging a lifespan, improving motor behavior in the subject, read on instant intended treatment outcome.
Pahan’ 000 is silent about vitamin A in combination with gemfibrozil.
Pahan’ 666 teaches combination of gemfibrozil and vitamin A may be a synergistic providing greater therapeutic effect in the subject than administration of vitamin A or the fibrate alone for treating lysosomal storage disorder.
Jana collectively teaches a novel myelinogenic property of gemfibrozil and gemfibrozil may be of therapeutic benefit in demyelinating diseases (which reads on claim 1).
It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instantly claimed invention to further explore gemfibrozil for treating other neurodegenerative disease (e.g. Krabbe disease), based on combined teachings of prior art and general knowledge of neurological disorder and arrived instantly claimed invention with reasonable expectation of success. A skilled artisan would be motivated to explore gemfibrozil for treating other neurodegenerative disease (e.g. Krabbe disease) since Krabbe disease is lysosomal storage disease that belongs to the same group of neurological disorder as taught by Pahan’ 000 and Pahan’ 666.
Regarding instantly claimed treatment outcome/ intended result, the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. A skilled artisan would reasonably expect gemfibrozil alone or in combination with vitamin A administered to a subject with Krabbe disease might provide an alternative treatment for Krabbe disease based on the neuroprotective properties of gemfibrozil taught by prior art with instant claimed treatment outcome which is the property/biological activity of gemfibrozil.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and exploration/optimization of for intended treatment outcome based on the general knowledge of treating neurological disorder (e.g. lysosomal disease, Krabbe disease). Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 9750712 B2.
Reference claims are directed to a method of for treatment of a neurodegenerative disease, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent that mediates upregulation of TPP1, the agent comprising a lipid-lowering drug, wherein the neurodegenerative disease is neuronal ceroid lipofuscinosis, wherein the lipid lowering drug is a fibrate.
Reference claims 2, 8 and 11 further recite the fibrate is gemfibrozil .
Reference claim 5 recites all-trans retinoic acid (which reads on vitamin A) .
Reference claim 6 recites administering all-trans retinoic acid and a fibrate provides a greater therapeutic effect in the subject than administration of all-trans retinoic acid or the fibrate alone.
The difference of instant claims and reference claims are targeted disease: Krabbe disease vs neuronal ceroid lipofuscinosis and intended treatment outcome.
It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound. A skilled artisan would have known both neuronal ceroid lipofuscinosis and Krabbe disease are lysosomal storage disease. It would have been obvious to one of the ordinary skilled in the art to further explore gemfibrozil alone or in combination with vitamin A for treating other lysosomal storage disease (e.g. Krabbe disease), based on combined beneficial teachings of reference claims and general knowledge of treating neurological disorder (e.g. lysosomal storage disease). A skilled artisan would be motivated to explore gemfibrozil alone or in combination with vitamin A for treating Krabbe disease because Krabbe disease is a lysosomal storage disorder associated with lysosomal function as neuronal ceroid lipofuscinosis.
Regarding instantly claimed treatment outcome/ intended result, the biological activity of compound is the property of active compound and products of identical or similar composition cannot exert mutually exclusive properties when administered under the same or similar circumstances. A skilled artisan would reasonably expect gemfibrozil alone or in combination with vitamin A administered to a subject with Krabbe disease might provide an alternative treatment for Krabbe disease based on the neuroprotective properties of gemfibrozil taught by reference claims.
The instant application shares at least one common inventor/applicant with the reference patent. Further, the continuing data of instant application is not related to the reference patent and thus no 35 USC 121 shield exists. See MPEP 804.01.
Claims 1, 3, 6, 7, 9-10, 12-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11020366 B2 .
Reference claims are directed to a method of decreasing neuronal apototic cell death in a subject having neuronal ceroid lipofuscinosis, comprising administering to the subject a composition comprising a therapeutically effective amount of gemfibrozil.
Reference claim 5 recites method of prolonging a lifespan of a subject having neuronal ceroid lipofuscinosis. Reference 7 recites a method of improving motor behavior of a subject having neuronal ceroid lipofuscinosis.
Reference claims are silent about Krabbe disease as targeted disease and intended treatment outcome thereof.
It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound. It would have been obvious to one of the ordinary skilled in the art to further explore gemfibrozil alone or in combination with vitamin A for treating other lysosomal storage disease (e.g. Krabbe disease), based on combined beneficial teachings of reference claims and general knowledge of treating neurological disorder (e.g. lysosomal storage disease). A skilled artisan would be motivated to explore gemfibrozil for treating Krabbe disease because Krabbe disease is a lysosomal storage disorder associated with lysosomal function as neuronal ceroid lipofuscinosis.
The instant application shares at least one common inventor/applicant with the reference patent. Further, the continuing data of instant application is not related to the reference patent and thus no 35 USC 121 shield exists. See MPEP 804.01.
Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11351142 B2.
Reference claims are directed to a method for treatment of a neurodegenerative disease, comprising administering to a subject in need of such treatment a composition comprising a therapeutically effective amount of an agent that mediates upregulation of TPP1, the agent comprising a lipid-lowering drug, wherein the neurodegenerative disease is a lysosomal storage disorder, and wherein the lipid-lowering drug is a fibrate, and wherein the lysosomal storage disease is Tay-Sach's disease.
Reference claim 2 and 7 recite the fibrate is gemfibrozil.
Reference claim 4 recites composition further comprises a therapeutically effective amount of all-trans retinoic acid (which reads on vitamin A) .
Reference claim 5 recites administering all-trans retinoic acid and a fibrate provides a greater therapeutic effect in the subject than administration of all-trans retinoic acid or the fibrate alone.
Reference claims are silent about Krabbe disease as targeted disease and intended treatment outcome thereof.
It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound. A skilled artisan would have known Krabbe disease are lysosomal storage disease. It would have been obvious to one of the ordinary skilled in the art to further explore gemfibrozil alone or in combination with vitamin A for treating other lysosomal storage disease (e.g. Krabbe disease), based on combined beneficial teachings of reference claims and general knowledge of treating neurological disorder (e.g. lysosomal storage disease). A skilled artisan would be motivated to explore gemfibrozil alone or in combination with vitamin A for treating Krabbe disease because Krabbe disease is a lysosomal storage disorder associated with lysosomal function as Tay-Sach's disease.
The instant application shares at least one common inventor/applicant with the reference patent. Further, the continuing data of instant application is not related to the reference patent and thus no 35 USC 121 shield exists. See MPEP 804.01.
Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11844767 B2.
Reference claims are directed to method for reducing amyloid-β protein aggregates in the brain of comprising administering to the subject in need of such treatment a composition comprising a therapeutically effective amount of a combination of vitamin A or a derivative thereof and an agonist of proliferator-activated receptor α (“PPARα”).
Reference claim 9 and 16 recite PPARα agonist is gemfibrozil.
Reference claims 14 and 15 recite Alzheimer's disease and Parkinson’s Disease.
Reference claims are silent about Krabbe disease as targeted disease and intended treatment outcome thereof. It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound. A skilled artisan would be motivated to explore gemfibrozil alone or in combination with vitamin A for treating Krabbe disease based on the beneficial teaching of reference claims with reasonable expectation that gemfibrozil alone or in combination with vitamin A might provide an alternative treatment for Krabbe disease with the intended treatment outcome/result.
The instant application shares at least one common inventor/applicant with the reference patent. Further, the continuing data of instant application is not related to the reference patent and thus no 35 USC 121 shield exists. See MPEP 804.01.
Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11135180 B2.
Reference claims are directed to method for reducing amyloid-β protein aggregates in the brain of a subject, the method comprising administering to the subject in need of such treatment a composition comprising a therapeutically effective amount of a combination of vitamin A or a derivative thereof and an agonist of proliferator-activated receptor α (“PPARα”), wherein the agonist of PPARα is gemfibrozil.
Reference claim 7 recites Alzheimer’ disease.
Reference claims are silent about Krabbe disease as targeted disease and intended treatment outcome thereof. It’s common practice to repurpose drugs and explore different pharmaceutical use of active compound. A skilled artisan would be motivated to explore gemfibrozil alone or in combination with vitamin A for treating Krabbe disease based on the beneficial teaching of reference claims with reasonable expectation that gemfibrozil alone or in combination with vitamin A might provide an alternative treatment for Krabbe disease with the intended treatment outcome/result.
The instant application shares at least one common inventor/applicant with the reference patent. Further, the continuing data of instant application is not related to the reference patent and thus no 35 USC 121 shield exists. See MPEP 804.01.
Conclusion
No claims are allowed.
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/L.M./Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628