DETAILED ACTION
Claims 1-2, 4-11, and 13-16, submitted 18 September 2025, are pending in the application and subject to examination. Claim 3 has been cancelled.
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 .
Rejections – Withdrawn and New
The status for each rejection in the previous Office Action is set out below.
Rejections under 35 U.S.C. § 112(a)
Applicant’s amendment of instant claim 1 is sufficient to overcome the rejection in the previous Office Action.
Rejections under 35 U.S.C. § 103
Applicant’s amendment of instant claims 1-2 and 10-11 and arguments, found on pages 2-8 of the Remarks, are sufficient to overcome the rejection in the previous Office Action.
Response to Arguments
Applicant’s arguments, see Applicant’s Arguments/Remarks, filed 18 September 2025, with respect to 35 U.S.C. § 112(a) and 35 U.S.C. § 103 have been fully considered and are persuasive. The rejections of claims 1-2, 4-11, and 13-15 has been withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 4-11, and 13-15 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 claim(s) contains 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.
Claim 1 recites “A method for the treatment of a disease of central nervous system comprising at least one step of administering a micelle containing at least one mTOR inhibitor…”, for which the specification does not provide adequate written description to convey that the inventors were in possession of the scope of the claimed invention.
The Examples, found on pages 13-19 of the instant specification are drawn to preparation of micelles containing everolimus, analysis of the micelles in physiological conditions, and in vitro experimentation which encompassed cell toxicity, stability, and effects on cervical cancer cell lines and neuroblastoma cell lines. Consequently, the instant specification does not teach the treatment of a disease of the central nervous system. In fact, on page 19 of the instant specification in the conclusion section, there appears to be a prophetic example by the use of the future tense. Moreover, the specification further points to the prophetic use of the instantly claimed invention by stating “As positive results were obtained in vitro, they can be repeated with rapamycin and further analyses can be conducted, centred on the use of the micellar solution of everolimus/rapamycin administered in vivo, in normal and AD mouse models and then in patients”. As the Applicant has provided no experimental data to suggest the treatment of a disease of the central nervous system and in view of the prophetic exemplification, the instantly claimed invention is not described in such a way as to reasonably convey to one skilled in the art that the inventor, at the time the application was filed, had possession of the instantly claimed invention.
Regarding the requirement for adequate written description, the Applicant is
directed to MPEP 2163 which states “An applicant shows that the inventor was in
possession of the claimed invention by describing the claimed invention with all of its
limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107
F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)”. Based on the language of
the specification and absence of supporting material, the Examiner concludes that the
Applicant does not have possession of the claimed invention.
Claims 2, 4-11, and 13-15 are rejected as they are dependent from the rejected independent claim.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 1-2, 4-11, and 13-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the use of everolimus in the treatment of cervical cancer and neuroblastoma, does not reasonably provide enablement for all mTOR inhibitors in the treatment of a disease of the central nervous system, nor does it reasonably provide enablement for the use of all micelles. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Breadth of the Claims
Claim 1 recites ““A method for the treatment of a disease of central nervous system comprising at least one step of administering a micelle containing at least one mTOR inhibitor…”. Claim 1 identifies the compounds being used by their biological function which creates uncertainty about what compound the claim is referencing and can thus be interpreted to include any mTOR inhibitor. As previously mentioned, the instant claim also makes reference to the use of a micelle. As there are various known types of micelles in the art, it is unclear what micelle the claim is referencing and thus can be interpreted to include any type of micelle.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to the treatment of a disease of the central nervous system by administering a micelle containing at least one mTOR inhibitor.
State of the Prior Art
The state of the prior art is what one skilled in the art would have known, at the
time the application was filed, about the subject matter to which the claimed invention
pertains. The relative skill of those in the art refers to the skill of those in the art at the
time the application was filed. See MPEP 2164.05(b). See Pac. Bioscience of Cal., Inc.
v. Oxford Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the
art and is related to the amount of direction or guidance needed in the specification as
filed to meet the enablement requirement. The state of the prior art is also related to the
need for working examples in the specification. See MPEP 2165.05(a).
The prior art teaches various types of compounds with varying structural configurations. For example, Mao et al. (Mao, Beibei, et al. "Overview of research into mTOR inhibitors." Molecules 27.16 (2022): 5295.) discloses multiple types of mTOR inhibitors such as mTOR allosteric inhibitors, ATP-competitive inhibitors, and dual binding site inhibitors (Abstract). Mao teaches the structures of allosteric inhibitors of mTOR in figure 3, shown below. Allosteric inhibitors include rapamycin and derivatives of rapamycin (i.e., temsirolimus, everolimus, and ridaforolimus) of which all have similar structures with the rapamycin backbone structure (pg. 5, Section “Rapamycin and It’s Derivatives”, 1st paragraph).
Figure 3 (pg. 5)
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Additionally, Mao discloses morpholine-substituted heterocyclic skeleton inhibitors in Figure 4, shown in part below, which consist of very different structures and also teaches wherein compounds R27, R28, and R29 can be used in the treatment of a disease of the central nervous system (pg. 13, Section “Other Structural Skeletal Inhibitors”, 3rd paragraph).
Figure 4, Compounds R27-R29 (pg. 7, 8th Col. Down)
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The prior art also teaches various types of micelles which can divided into groups being hydrophilic or hydrophobic (Abstract) and further into the subgroups of normal micelles, which can be star-like or crew-cut micelles (pg. 3, Section “Types of Micelles”, Left Col., 2nd paragraph and Right Col., Fig. 1), the micelle can be a reverse micelle (pg. 4, Section “Types of Micelles”, Left Col., Fig. 2), or it can be a unimolecular micelle, which are made up of a single block copolymer containing hydrophobic and hydrophilic regions on a single molecule (pg. 4, Section “Unimolecular micelle”, Left Col., 1st paragraph), as taught by Honarmand et al. (Honarmand, S., et al. "Micelles-based systems and their versatile application in different industries." Journal of NanoScience Technology (2023)). Honarmand also discloses the morphology of a micelle, being either spherical, cylindrical or vesicle affects the circulation half-life, biodistribution, and cellular uptake (pg. 5, Section “Morphology of micelles”, Right Col., 1st and 2nd paragraph.).
Level of Skill in the Art
The person of ordinary skill in the art is a person who is presumed to have known the relevant art at the relevant time. Factors that may be considered in determining the level of ordinary skill in the art may include: (A) "type of problems encountered in the
art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations are made;" (D) "sophistication of the technology; and" (E) "educational level of active workers in the field. In a given case, every factor may not be present, and one or more factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121 (Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955, 962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP 2141.03 (I).
The invention described pertains to the medical or pharmaceutical arts. One of ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art field with a Ph. D or other advanced degree in these or other related fields.
Level of Predictability in the Art
The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 427, F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed,
that teaches exactly how to make or use the invention. The more that is known in the
prior art about the nature of the invention, how to make, and how to use the invention,
and the more predictable the art is, the less information needs to be explicitly stated in
the specification. In contrast, if little is known in the prior art about the nature of the
invention and the art in unpredictable, the specification would need more detail as to
how to make and use the invention in order to be enabling. The scope of the required
enablement varies inversely with the degree of predictability involved, but even in
unpredictable art, a disclosure of every operable species is not required. A single
embodiment may provide broad enablement in cases involving predictable factors, such
as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ
122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA
1971). However, in applications directed to inventions in arts where the results are
unpredictable, the disclosure of a single species usually does not provide an adequate
basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA
1938). In cases involving unpredictable factors, such as most chemical reactions and
physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166
USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide
more objective evidence to support the enablement of the aforementioned claims to
contrast the unpredictability of the subject matter art.
There is unpredictability in the field of endeavor in regards to the currently claimed method of treating a disease of central nervous system comprising at least one step of administering a micelle containing at least one mTOR inhibitor. There is unpredictability in the pharmaceutical arts with the practice of the treatment of all diseases of the central nervous system with a single compound.
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of the unpredictability of the art. Given the context and scope of the claims mentioned above, the inventor failed to provide the necessary amount of direction for one skilled in the art to adequately use the invention across all suggested utility in the broadly stated disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant has provided guidance on the preparation of micelles loaded with everolimus, found on pages 13-14 of the instant specification, using DSPE-PEG2000 micelles. Applicant has also provided guidance on the stability of the drug-loaded micelle under biological conditions, found on pages 14-15 of the specification. Further, the Applicant provided guidance on the everolimus loaded micelles on the HeLa cell line, which is a cervical cancer cell line, and the SH-SY5Y cell line, which is a neuroblastoma cell line, found on pages 17-19 of the instant specification.
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the
predictability of the art, and the direction provided by the inventor. For one skilled in the art to practice the invention as disclosed, the artisan trying to practice Applicant’s
claimed invention would be required to undertake unduly burdensome activities
including:
Experimentation to demonstrate application of the everolimus loaded micelle in a disease of the central nervous system, specifically the elected species of Alzheimer’s Disease.
Experimentation to demonstrate application of the invention with various types of mTOR inhibitors.
Experimentation to demonstrate application of the invention with various types of micelles.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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JUSTIN CHRISTOPHER. SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622