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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on April 30, 2026 has been reviewed by the examiner and entered of record in the file.
3. Claim 1 is amended.
4. Applicant’s previously elected the species of single PPARb ligand: MePA.
5. Claims 2, 3, and 5-8 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected subject matter without traverse, there being no allowable generic or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.
6. Claims 1, 4, 9, 10, 15 and 16 are under examination with the elected species and are the subject of this office action.
Claim Objections
7. Claim 1 is objected to because of the following informalities: a comma is missing at the end of line 6, after the term “2,6-DBP)”.
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 Gostelli, 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 an in vitro 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. Applicant proposes future studies to determine promotion of myelination by PPARb ligands in murine models of demyelinating diseases in paragraphs [0078]-[0079], however there is no data or evidence of modulating cells other than neuronal or oligodendroglial progenitor cells (OPC) with the agents of claim 1.
16. Applicants do not have possession of stimulating PPARb activity in all types of cells 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 any/all of the agents of claim 1 stimulate PPARb in cells in 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.
Response to Arguments
22. Applicant has amended claim 1 to incorporate the limitation “in vitro” into line 1 of claim 1, which Applicant alleges renders the previous written description rejection moot.
23. Applicant's arguments have been fully considered but they are not persuasive. It is noted that while Applicant amends claim 1 to add the limitation of “in vitro” to the preamble, the claim still embraces a method of administering any of the recited PPARb ligands to any cell, not just CNS or OPC cells.
24. There is no data or evidence of stimulating cells other than neuronal or oligodendroglial progenitor cells (OPC) with the agents of claim 1, as the preamble recites.
Applicants do not have possession of stimulating PPARb activity in all types of cells in an in vitro environment because the PPARb can be stimulated in vitro in non-neuronal cells like astroglia or liver cells or heart cells or immune cells etc. as PPARb is expressed there as well, in addition to CNS/neuronal and/or OPC cells.
New Claim Rejections - 35 USC § 112(b)
25. 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.
26. Claims 15 and 16 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.
27. This rejection is necessitated by Applicant’s amendment to claim 1.
28. Claim 15 depends from claim 1, which as amended, is directed to an in vitro method of stimulating PPARb in a cell. Claim 15 further limits wherein the effective amount of the PPARb ligand promotes myelination in the CNS, however there is insufficient antecedent basis for promoting myelination in the CNS because an in vitro culture cannot comprise a central nervous system (CNS).
29. Claim 16 depends from claim 1, and recites the limitation wherein the PPAR ligand “increases differentiation of OPC to oligodendrocytes”, [emphasis added], i.e., plural oligodendrocyte. However, the recitation of plurals is confusing because claim 1 is drawn to stimulating PPARb in a cell, wherein the cell is an oligodendroglial progenitor cell (OPC), i.e., a singular OPC cell. A single OPC cell cannot differentiate into multiple oligodendrocytes. Clarification is requested.
Previous Claim Rejections - 35 USC § 102
30. Claims 1, 4, 9, 10, 15 and 16 were previously rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang et al., Biomedicine & Pharmacotherapy (published March 2019).
31. In view of Applicant’s amendatory changes to limit the claimed method to an in vitro method, the previous anticipation rejection is withdrawn.
New Claim Rejections - 35 USC § 103
32. 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.
33. 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.
34. Claims 1, 4, 9, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Scutt and Still, U.S. 2003/0139372 A1, as evidenced by Duan et al. (Fundamental Research 2024).
35. This rejection is newly applied as necessitated by Applicant’s amendment to the claims.
Claim 1 is directed to an in vitro method of stimulating peroxisome proliferator-activated receptor b (PPARb) activity in a cell, comprising: administering an effective amount of a PPARb ligand, 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),
(more specifically, methyl palmitate (MePA), (claim 4)),
wherein the cell is cell is a central nervous system (CNS) cell (claim 9) or an oligodendroglial progenitor cell (OPC).
36. Scutt teaches an in vitro method of screening agents which modulate the activity of PPAR transcription factors, comprising:
i. providing a culture of bone forming cells;
ii. exposing the bone forming cells to an agent capable of modulating the activity of at least one PPAR transcription factor; and
iii. monitoring the effect of the agent on the bone forming capacity of the cell culture,
wherein a preferred agent is methyl palmitate and the preferred class of compounds are PPARb activators (i.e., stimulators) (see paragraphs [0042], [0046], and [0058]-[0061]).
37. Regarding the “culture of bone forming cells” in step i., Scutt teaches that said culture(s) are comprised of fibroblasts (see Preparatory Example at paragraphs [0076]-[0077], Fibroblastic Colony Forming Unit Cultures). And, it is clear as evidenced by Duan et al. that fibroblast cells serve an important role in the CNS:
“In the CNS, fibroblasts are mostly distributed in the meninges, perivascular Virchow-Robin space, and choroid plexus [8] ( Fig. 1a)… Fibroblasts, pericytes, and SMCs all express PDGFR 𝛽; fibroblasts are in addition PDGFR 𝛼 positive, a marker that they share with oligodendrocyte precursor cells.”
(see page 262, right column, under “Characteristics of CNS fibroblasts.”
38. And, Scutt goes on to teach that methyl palmitate stimulates PPAR activity in said fibroblast culture (see Example, paragraph [0087]). Thus, given that the genus of preferred PPAR activators disclosed by Scutt is small, and methyl palmitate is specifically employed in the working example, one of skill in the art before the effective filing date of the claimed invention would have immediately envisaged selecting methyl palmitate for use in a method of stimulating PPARb in vitro in a culture of fibroblasts (i.e., CNS cells), with a reasonable expectation of success.
As such, claims 1, 4 and 9 are prima facie obvious.
39. Claims 10 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Scutt and Still, U.S. 2003/0139372 A1, as evidenced by Duan et al. (Fundamental Research 2024), as applied to claims 1, 4, 9, and 16 above, and further in view of Di Loreto et al., Journal of Cellular Physiology (2007), as evidenced by Mironova et al., Science (2026).
Claim 1 is addressed in detail, above.
Claim 10 is drawn to claim 1, wherein the cell is an oligodendroglial progenitor cell (OPC).
Claim 16 is drawn to claim 1 and limits wherein the effective amount of the PPARb ligand increases differentiation of OPC to oligodendrocytes.
40. Scutt et al. as evidenced by Duan et al. suggest a method of administering methyl palmitate in vitro for stimulating PPARb in a culture of fibroblasts (i.e., CNS cells), but do not the teach that the cell is an OPC.
41. However, Di Loreto et al. teach that the PPARb isotype is involved in oligodendrocyte neuronal differentiation (see page 837, left column, last paragraph). And, it is clear as evidenced by Mironova et al. that oligodendrocytes are central nervous system (CNS) cells that differentiate progressively from oligodendrocyte progenitor cells (aka OPC aka oligodendroglial cells), (page 368, left column, first two paragraphs).
42. As such, by virtue of administering methyl palmitate in vitro to stimulate the activity of a PPARb in a CNS cell, one of skill in the art is necessarily increasing differentiation of OPC cells to oligodendrocytes. The fact that Applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
43. Therefore, it would have been obvious to one of skill in the art before the effective filing date of the claimed invention that a method of stimulating PPARb comprising the administration of methyl palmitate to a CNS cell in vitro would necessarily increase differentiation from OPCs to oligodendrocytes, with a reasonable expectation of success.
As such, claims 10 and 16 are prima facie obvious.
Conclusion
44. 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.
45. 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
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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