DETAILED ACTION
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 . 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.
Claim Rejections - 35 USC § 112 – Scope of Enablement
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.
Claim 17 is rejected under 35 U.S.C. 112(a) because the specification, while being enabling for some conditions such as asthma, does not reasonably provide enablement for treating other conditions such as cancer, Alzheimer’s disease, cardiovascular disease, diabetes, and anti-aging (which are age-related diseases). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).1
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention, state and predictability of the art, and relative skill level: The invention relates to methods for the treatment and prophylaxis of age-related diseases and disorders. The invention also relates to methods for anti-aging therapy. The relative skill of those in the art is high, that of an M.D. or Ph.D. That factor is outweighed, however, by the unpredictable nature of the art. As illustrative of the state of the art, the Examiner cites Richardson et al. (Experimental Gerontology, 2015, vol. 68, pages 51-58). While Richardson et al. notes that there is speculation that rapamycin has ‘anti-aging’ properties (abstract), this is stated as speculation. And further with respect to diseases such as Alzheimer’s, while rapamycin has shown to affect memory in mouse models of the disease (such as discussed in the abstract), there is yet no treatment for the disease itself and rapamycin has not been shown to treat Alzheimer’s disease as of the time of publishing (page 57, first full paragraph).
Also, the Examiner cites Schindler et al. (Am. J. Physiol. Regul. Integr. Comp. Physiol., 2014, vol. 307, pages R434-R443), which states that rapamycin can cause diabetes in mice (abstract). Further, Schindler et al. states that there is a recognized “rapamycin paradox” which highlights the gap in our understanding the effects of rapamycin and the mechanisms by which they occur (page R434, second paragraph).
The Examiner further cites Scheibye-Knudsen ("Antitumor Potential and Other Emerging Medicinal Properties of Natural Compounds," 2013, Springer Science, Chapter 16, pages 239-247) as illustrative of the state of the art. While rapamycin is stated to be receiving growing attention (abstract), this is mainly in the form of potential (e.g. cardiovascular protection – section 16.3.2 & neurodegenerative disorders – section 16.3.4). Scheibye-Knudsen states that while the potential of rapamycin seems limitless, nothing gold can stay, and several trials have shown disappointing results (section 16.4).
These all relate to rapamycin, which is the parent drug of the class of agents such as everolimus, and no further guidance as to these members of the rapamycin composition class has been provided in the specification either.
The Examiner cannot ascertain the predictability of the art, as there appears to be no guidance in the art as to how to make and use the full scope of the invention.
The breadth of the claims: The claims are broadly drawn to anti-aging therapy and a variety of diseases and disorders associated with age, such as cancer, Alzheimer’s disease, cardiovascular disease, and diabetes.
The amount of direction or guidance provided and the presence or absence of working examples: The specification provides no direction or guidance for practicing the claimed invention in its “full scope”. No reasonably specific guidance is provided concerning useful therapeutic protocols for any of the treatments, disorders, or diseases claimed, other than by providing examples which show that that rapamycin is delivered.
The quantity of experimentation necessary: Because of the known unpredictability of the art, and in the absence of experimental evidence, no one skilled in the art would accept the assertion that the instantly claimed composition could be predictably used to treat most of the diseases, disorders, and anti-aging as inferred by the claim and contemplated by the specification. Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the claimed invention in its “full scope” a person of ordinary skill in the art would have to engage in undue experimentation, with no reasonable expectation of success.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
Claims 1-8 and 10-14 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US Patent Application Publication 2008/0175887).
Wang discloses methods of treating respiratory disorders such as asthma by administering, preferably pulmonarily, anti-inflammatory or anti-proliferative drugs (abstract). The drug can be everolimus (paragraph [78]). The drug can be administered as a dry powder (paragraph [49]), and such powders containing the drug and an additive are microparticles sized between 1 and 2 microns (paragraph [61]). Wang further teaches a diluent is present, which can be lactose or mannitol (paragraph [66]), which reads upon the carrier instantly recited.
Thus, Wang discloses compositions comprising the individual elements of the instantly recited composition (carrier, sirolimus or everolimus, and the form of an inhalable dry powder) and together these would provide a composition as instantly recited. However, Wang is not anticipatory insofar as these combinations must be selected from various lists/locations in the reference. It would have been prima facie obvious, however, to make the combination since each component is taught as being useful in making the compositions of the prior art. Since this modification of the prior art represents nothing more than the predictable use of prior art elements according to their established functions a prima facie case of obviousness exists. See MPEP 2141.
Instant claim 2 recites a limitation to the amount of the drug in the powder. And Wang discloses drug is present in from 1 to 99 wt% (paragraph [149]), a range which overlaps the instantly recited range. And in cases involving overlapping ranges, where the instantly claimed ranges “overlap or lie inside ranges disclosed by the prior art”, a prima facie case of obviousness exists. See MPEP 2144.05(A).
Instant claim 3 further limits the size of the drug particles, and the drug-containing powder particles are sized between 1 and 2 microns (paragraph [61]), a range which reads upon or overlaps each of the ranges instantly recited.
Instant claims 4 and 6 recite limitations to the carrier. Wang teaches a diluent is present, which can be lactose or mannitol (paragraph [66]), which are each an option instantly recited. Instant claim 7 recites that two such carriers are used, and each of both lactose and mannitol are suggested, and the use of the combination of the two would have been prima facie obvious. Generally, it is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for same purpose, in order to form a third composition to be used for the very same purpose. The idea for combining them flows logically from their having been individually taught in the prior art. See MPEP 2144.06.
Instant claims 5, 7, and 8 recite that one of the two carries is sized from 30 to 100 microns and the other is less than 10 microns, and can both be lactose. The above cited section of Wang suggests 1-2 microns for particles which are delivered to the deep lung (paragraph [61]). And additional sizes taught with respect to inhalation delivery useful include greater than 5 microns (for oral absorption) and about 2 to about 5 microns (upper pulmonary region) (paragraph [54]), and these ranges overlap the instantly recited range.
Claim 10 recites the further inclusion of a surfactant additive. Wang teaches that suitable additives can be surfactants, including those within the scope of this claim (paragraph [93]).
Instant claim 11 recites that the composition “consists essentially of” the microparticles of drug and the particles of the carrier. The instant specification does not provide a clear indication what the basic and novel characteristics actually are for the claimed invention, and as such the transitional phrase “consisting essentially of” will be construed as equivalent in meaning to the term "comprising.” See MPEP 2111.03(III) & PPG v. Guardian, 156 F.3d 1351, 1354 (Fed. Cir. 1998). Dependent instant claims 12-14 recite compositions with the above discussed limitations.
Claim 9 is (and the above cited claims 1-8 and 10-14 are) rejected under 35 U.S.C. 103 as being unpatentable over Wang (US Patent Application Publication 2008/0175887) as applied to claim 1 above, and further in view of Li et al. (US Patent Application Publication 2023/0100760).
Instant claim 9 limits the isomeric B:C ratio of the everolimus, temsirolimus, ridaforolimus, umirolimus, and/or zotarolimus. There is no support for this limitation in the instant specification, as isomers and ratios thereof are only discussed for rapamycin (see paragraph [74]). There also is no support for isomers of these drugs in any of the parent patent applications as well. Thus, the effective filing date of instant claim 9 is considered 23 April 2024, the actual filing date of the instant application.
Wang teaches most of the limitations recited by instant claim 9, except for the isomer of everolimus used. This drug generally is suggested, but no discussion of the specific isomeric forms is provided.
Li et al. remedies this deficiency, as Li et al. discusses purified forms of everolimus (paragraph [28]), which comprise less than 0.1% of the undesirable isomers A and C and are primarily isomer B (id.).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have used the everolimus as disclosed by Shaw et al., being primarily the B isomer, in the composition taught by Wang. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07.
Allowable Subject Matter
Claims 15 and 16 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter. With respect to claims 15 and 16, the closest prior art is considered to be above cited Wang (US Patent Application Publication 2008/0175887). Wang discloses methods of treating respiratory disorders by administering, preferably pulmonarily, rapamycin (abstract). The drug can be administered as a dry powder and the powders contain the drug and an additive. However, the instantly claimed invention excludes anything other than the drug (rapamycin) and carrier particles, with additives and surfactants both excluded from the composition.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Gulledge whose telephone number is (571) 270-5756. The examiner can normally be reached Monday - Friday 7am - 4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at (571) 272-3311. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Brian Gulledge/Primary Examiner, Art Unit 1699
1 As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.