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 .
Response to Amendment and
Status of the Claims
2. Applicant’s amendment and response, submitted September 12, 2025, has been reviewed by the examiner and entered of record in the file. Claims 1, 9 and 10 are amended, and claims 11-14 are canceled.
3. Applicant’s previously elected the species of (a) the single PPARb ligand: MePA; (b) the type of cell in which PPARb activity is modulated: OPC; (c) the single disorder to be treated: MS; and (d) the route of administration: oral.
4. Claims 2, 3, and 5-8 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter without traverse, there being no allowable generic or linking claim.
5. Claims 1, 4, 9, 10, 15 and 16 are under examination with the elected species and are the subject of this office action.
Previous Claim Rejections - 35 USC § 112(b)
6. Claims 1-16 were previously rejected for reciting a method of “modulating peroxisome proliferator-activated receptor b (PPARb) activity in a cell in a subject in need thereof…” because it is unclear what is embraced by the term modulating," because the term “modulating” encompasses both inhibition and enhancement. In view of Applicant’s amendment to clarify that the method is directed to stimulating PPARb activity, the previous indefiniteness rejection is withdrawn.
7. Claim 12 was previously rejected as being indefinite for lacking antecedent basis. In view of the cancelation of claim 12, the previous indefiniteness rejection is withdrawn.
Previous Claim Rejections - 35 USC § 112(a)
8. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
9. Claims 1, 4, 15, and 16 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection has been modified as a result of Applicant’s amendment to the claims.
10. As the Federal Circuit has stated: The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP does state that for a generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad generic. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872, F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989).
11. The factors considered in the Written Description requirement are:
(1) level of skill and knowledge in the art,
(2) partial structure,
(3) physical and/or chemical properties,
(4) functional characteristics alone or coupled with a known or disclosed
correlation between structure and function, and
(5) the method of making the claimed invention.
12. Level of skill and knowledge in the art: The level of skill to practice the art of the instantly claimed invention is high and requires a variety of skills usually found in institutions and companies that employ highly trained and skilled scientists to carry out these tasks.
13. Partial structure; Physical and/or chemical properties; and Functional characteristics: Claim 1 is drawn to a method of stimulating peroxisome proliferator-activated receptor b (PPARb) activity in a cell, wherein the cell is cell is a central nervous system (CNS) cell or an oligodendroglial progenitor cell (OPC), the method comprising: administering an effective amount of a PPARb ligand to the subject, the PPARb ligand selected from the group consisting of 1,3-Di-tertbutyl benzene (DBB), 2,4-Di-tertbutyl phenol (DBP), Methyl palmitate (MePA), 2,6-Di-tertbutyl-4-Methyl Phenol (DBMP), 3,4-Di- tertbutyl- Phenol (3,4-DBP), 2,3 -Di-tertbutyl- Phenol (2,3-DBP), and 2,6-Di-tertbutyl-Phenol (2,6-DBP). The scope of the agents to be used is limited to the above PPARb ligands but the scope of the cells in a subject where in the modulation of PPARb activity occurs is large.
14. The instant specification teaches that PPARb belongs to a class of nuclear hormone receptors that participate in a diverse range of biological functions including control of fatty acid transport and catabolism, anti-inflammation, immuno-modulation, and anti-oxidation, wherein PPARb is primarily expressed in CNS cells, in particular oligodendrocytes (paragraph [0004]). The specification provides experimental data identifying and characterizing cerebellar ligands of PPARb in vitro in cultured oligodendrocytes (paragraphs [0044]-[0051]); and demonstrates that certain of the PPARb ligands (DBB, DBP and MePA) stimulate differentiation of oligodendroglial progenitor cells (OPC) to oligodendrocytes to promote myelination (paragraphs [0052]-[0054] and Figures 1A-1D, 1S and 3A-3J).
15. While Applicant proposes future in vivo studies to determine promotion of myelination by PPARb ligands in murine models of demyelinating diseases in paragraphs [0078]-[0079], there is no data or evidence of (i) modulating cells other than neuronal or oligodendroglial progenitor cells (OPC) with the agents of claim 1, or (ii) modulating cells in subjects with any demyelinating disorder whatsoever.
16. Applicants do not have possession of stimulating PPARb activity in all types of cells in a subject or in an in vitro environment because the PPARb can be modulated in non-neuronal cells like astroglia or liver cells or heart cells or immune cells etc. as they are expressed there as well, in addition to neuronal and OPC cells.
17. Despite the advanced training of those in the art, the pharmaceutical art is highly unpredictable. It is still not possible to predict the pharmacological activity or treatment efficacy of a compound based on the structure alone. Typically, in order to verify that a compound will be effective in a method or treating a disease, the compounds must be either tested directly in a patient or in a model that has been established as being predictive of efficacy. It is not predictable from the specification or from the prior art that the agents of claim 1 stimulate PPARb in the cells of a subject or in a culture, i.e., in vitro.
18. The level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. Ariad, 598 F.3d at 1351, 94 USPQ2d at 1172; Capon v. Eshhar, 418 F.3d 1349, 1357-58, 76 USPQ2d 1078, 1083-84 (Fed. Cir. 2005). The fields of biology and chemistry are considered “unpredictable” because the complexity and unpredictability of chemical and biological interactions can make it difficult to understand the exact properties of an invention. A person of ordinary skill in the art from the specification or from the prior art cannot predict the pharmacological effects of administration of the instant formulation in subjects in regards to prevention of pain. The pharmaceutical industry is the prototypical example of a highly unpredictable field. Pfizer v. Teva Pharm., 482 F.Supp.2d 390, 413 (D.N.J. 2007); 2 Chisum on Patents § 5.04.
19. Applicants have failed to provide guidance or data or evidence as to how the skilled artisan would be able to extrapolate from the disclosure to use the claimed invention. “A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F 3d at 923; Eli Lilly, 119 at 1568. Instead, the “disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described.” Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear the "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116).
20. The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
21. Accordingly, it is deemed that the specification fails to provide adequate written description for the claimed invention and does not reasonably convey to one skilled in the relevant art that the inventors had possession of the entire scope of the claimed invention.
22. Claims 11 and 12 were previously rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as lacking enablement.
23. In view of the cancellation of claims 11 and 12, the previous enablement rejection is withdrawn.
Response to Arguments
24. Applicant has amended claim 1 to remove “in a subject in need thereof” and to cancel claims 11-14, which Applicant alleges renders the previous description and enablement rejections moot.
25. Applicant's arguments have been fully considered but they are not persuasive. It is noted that Applicant’s amendment to delete the recitation of “in a subject in need thereof” does not per se limit the claims to in vitro or ex vivo assay/ method, because as currently drafted, the claims still embrace any method of administering a PPARb ligand to a CNS or OPC cell, including in vivo in a subject.
26. There is no data or evidence of (i) stimulating cells other than neuronal or oligodendroglial progenitor cells (OPC) with the agents of claim 1, either in vitro or in vivo, or (ii) modulating cells in subjects with any demyelinating disorder whatsoever.
27. Applicants do not have possession of stimulating PPARb activity in all types of cells in a subject or in an in vitro environment because the PPARb can be stimulated in vitro and/or in vivo, in non-neuronal cells like astroglia or liver cells or heart cells or immune cells etc. as they are expressed there as well, in addition to neuronal and OPC cells.
Previous Claim Rejections - 35 USC § 102
28. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
29. Claims 1, 4, 9, 10, 15 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al., Biomedicine & Pharmacotherapy (published March 2019).
Claim 1 is directed to method of stimulating peroxisome proliferator- activated receptor b (PPARb) activity in a cell,
comprising administering an effective amount of a PPARb ligand (more specifically, methyl palmitate (MePA), (claim 4)),
wherein the cell is cell is a central nervous system (CNS) cell or an oligodendroglial progenitor cell (OPC), (more specifically in an OPC (embraced by claim 10)),
Claim 15 is drawn to claim 1 and limits wherein the effective amount of the PPARb ligand promotes myelination in the CNS.
Claim 16 is drawn to claim 1 and limits wherein the effective amount of the PPARb ligand increases differentiation of OPC to oligodendrocytes.
30. Zhang et al. teach a method of orally administering methyl palmitate (MP) to a mouse in an effective amount of 75 mg/kg/day, 150 mg/kg/day, or 300 mg/kg/day, in order to treat NASH in said mouse (see abstract).
31. Note that while Zhang et al. do not teach the inherent property of the instantly claimed compound to stimulate PPARb activity in a CNS cell that is an OPC, this result flows from the administration step itself. MPEP § 2112 (II) states "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." Furthermore, Integra Life Sciences I Ltd. v. Merck KGaA, 50 USPQ2d 1846 (DC SCalif, 1999) makes clear that a reference teaching a process may anticipate claims drawn to a method comprising the same process steps, despite the recitation of a different intended use in the preamble or the later discovery of a particular property of one of the starting materials or end products.
32. In the instant case, the claim has not defined either (a) a patient population, or (b) an in vitro environment and the active step recited in the body of the claim (i.e., administration of an effective amount of methyl palmitate) is identical to that taught by Zhang et al. It is noted that Applicant’s amendment to delete the recitation of “in a subject in need thereof” does not limit the claims to in vitro or ex vivo assays/ methods, because as currently drafted, the claims embrace any method of administering a PPARb ligand to a CNS or OPC cell, including in vivo.
34. See also Hoffer v. Microsoft Corp., 405 F.3d 1326 (Fed. Cir. 2005), noting that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited” (quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373 (Fed. Cir. 2003)). Although the Hoffer court was discussing the weight of a whereby clause, the reasoning applies equally to the weight of a preamble. In the instant case, as discussed above, the preamble (i.e., modulating PPARb activity in a cell) simply expresses the intended result of a process step positively recited, (i.e., administering an effective amount of methyl palmitate).
35. See also In re King, 801 F.2d 1324 (Fed. Cir. 1986), noting that “[u]nder principles of inherency, if a structure in the prior art necessarily functions in accordance with the limitations of a process or method claim of an application, the claim is anticipated. This is not to say that the discovery of a new use for an old structure based on unknown properties of the structure might not be patentable to the discoverer as a process... [but] if a previously patented device, in its normal and usual operation will perform the function which an appellant claims in a subsequent application for a process patent, then such application for process patent will be considered to have been anticipated by the former patented device.”
36. Claims 15 and 16 are drafted in terms of the desired outcome of the administration of the PPARb ligand of claim 1: “...wherein effective amount of the PPARb ligand promotes myelination in the CNS,” or “wherein the effective amount of the PPARb ligand increases differentiation of OPC to oligodendrocytes.” However, the administration of methyl palmitate to a subject is known. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, Applicant's recognition of the benefit is not in itself sufficient to distinguish the claimed composition from the prior art, In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1991). In this case, the ability of methyl palmitate to “promote(s) myelination in the CNS” or “increase(s) differentiation of OPC to oligodendrocytes” are considered latent properties of the administration of methyl palmitate disclosed by Zhang et al. and the alleged unexpected result does not confer patentability.
Response to Arguments
37. Applicant traverses the anticipation rejection, arguing that Zhang does not disclose a method of stimulating PPAR3 in CNS or OPC cells as recited in amended claim 1 (wherein claim 1 is amended to specify the cell types of CNS or OPC cells).
Applicant contends that Zhang is silent regarding PPARb activity in the brain and does not provide any guidance or rationale for one skilled in the art to use methyl palmitate for this purpose. Applicant argues that Zhang teaches methyl palmitate binding and activating PPARa whereas the instant application shows that methyl palmitate has no measurable binding for PPARa and is a specific biological ligand of PPARb in cerebellum with an EC5O of 50 nM (Specification at paragraph [0045]). Applicant alleges that Zhang does not motivate or direct one to use methyl palmitate specifically to activate PPARb in CNS or OPC cells.
38. Applicant's arguments have been fully considered but they are not persuasive. It is noted that the claim has not defined either (a) a patient population (in vivo) or (b) an in vitro or ex vivo environment, such that the recited method still embraces administration to a subject. The active step recited in the body of the claim (i.e., administration of an effective amount of methyl palmitate) is identical to that taught by Zhang et al. It is noted that Applicant’s amendment to delete the recitation of “in a subject in need thereof” does not limit the claims to any identifiable in vitro or ex vivo assay/ method, because as currently drafted, the claims embrace any method of administering a PPARb ligand because a recipient subject or cell has not been identified in line 3 of the claim.
Conclusion
39. In conclusion, claims 1-10, 15 and 16 are present in the application. Claims 2, 3, and 5-8 are presently withdrawn from consideration. Claims 1, 4, 9, 10, 15 and 16 are rejected. No claim is presently allowed.
40. THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
41. Any inquiry concerning this communication or earlier communications from the examiner should be directed to JANET L COPPINS whose telephone number is (571)272-0680. The examiner can normally be reached Monday-Friday 8:30AM-5PM EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JANET L COPPINS/Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628