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 .
Claims 1-11, 13, 15, 16, 18, 22, 23, 26, 28, 30 are before the Examiner.
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.
Claim(s) 1-3, 8-11, 13, 15, 16, 18, 22, 23, 26, 28, 30 are rejected under 35 U.S.C. 103 as being unpatentable over Behl WO2000015206. Landau WO2014056939 and Osornio Journal of Organic Chemistry (2012), 77(23), 10583-1059.
Behl teaches that tryptophanyl esters are useful for prophylaxis and treatment of oxidative pathol. processes in degenerative diseases and/or carcinomas. Preferred compounds are tryptophan octyl ester, N-oleoyltryptophan Et ester, and N-dodecanoyltryptophan Et ester. The compounds are used for treatment and/or prophylaxis of neurodegenerative diseases, cataracts, neoplastic diseases, and/or cardiovascular diseases, especially for Alzheimer's disease, Parkinson's disease, stroke, amyotrophic lateral sclerosis, cancer, arteriosclerosis, and/or myocardial infarction. Thus, tryptophan octyl ester (≥4 nM) protected human neuroblastoma cells in vitro from oxidative stress damage
Behl teaching include compounds
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which fall under the scope of the base claim formula or obvious variants (for example with respect to R1 of claim 2 lower homolog and claim 8 higher with respect to 2 alkenyls in L of formula I).
Landau teaches compounds for use as additives in a lipidic cubic phase material, and to novel lipidic cubic phase materials. These materials are biocompatible, stable and transparent and can encapsulate active compounds such as drugs and release them at will by chemical and/or photochemical triggering. A method of controlled release of a predetermined active compound, comprises the steps of: forming a lipidic cubic phase material by mixing a lipophilic component and a hydrophilic component comprising an aqueous solution containing the active compound; placing the lipidic cubic phase material in a region of interest; releasing the active compound by subjecting the lipidic cubic phase material to a chemical or photochemical stimulus.
Landau last compound at bottom of page 28, RN 261734-93-4,
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The above Landau compound falls under the scope of the formula I, except the L ester group is C2 alkyl, a lower homolog of the claimed compounds.
Likewise, Osornio titled “Design and Synthesis of Lipids for the Fabrication of Functional Lipidic Cubic-Phase Biomaterials” teaches series of novel lipids with designed functionalities. These lipids are based on conjugation of α-amino acids and their esters, cationic, anionic, neutral, and photochromic moieties to the lipophilic 9-cis octadecenyl chains by amide, ester, thioester, or amine bonds. Because of the plasticity of lipidic cubic phases, it is envisaged that when mixed with mono-oleoyl-rac-glycerol (mono-olein, MO) and water at appropriate proportions, they would assemble to form bi-continuous lipidic cubic phases (LCPs) that exhibit the well-known material properties of LCPs such as phase stability, optical transparency, and chem. permeability.
The compounds of Osornio such as
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as with Landau compounds, differ from the instance formula L groups.
Taken together Behl, Landau and Osornio teach that the lipophilicity can be modified by derivatizing tryptophan with long chain different L part of the lipid can be modified without comprising intended pharmaceutical use in lipid formulations.
Limitations of dependent claims 10-11, 13, 15, 16, 18, 22, 23, 26, 28, 30 are drawn to intended use that overlap with pharmaceutical use of compounds. Though the specific use as instantly recited are not explicitly taught in the cited references, there is suggestion of the claimed use based on the inherent lipidic nature of the tryptophan derivatives, for example because of the plasticity of lipidic cubic phases as taught by Landau and Osornio (for encapsulation of drugs). Further nothing in the specification for secondary considerations with respect to method of use. Example 2 talks about encapsulation but there is no comparative data for example as there is no working example.
Examination guidelines as to the position taken is predicated on the following:
The new use for an old compound must be novel as to the use directed and unobvious. The new use (if any) must account for the possibility that the underlying mechanism for the new therapy is the same mechanism that allows for a prior art treatment using the same compound (or its obvious version).
The discovery of a new use for an old structure based on unknown properties of the structure might be patentable to the discoverer as a process of using. In re Hack, 245 F.2d 246, 248, 114 USPQ 161, 163 (CCPA 1957). However, when the claim recites using an old composition or structure and the “use” is directed to a result or property of that composition or structure, then the claim is anticipated. In re May, 574 F.2d 1082, 1090, 197 USPQ 601, 607 (CCPA 1978) (Claims 1 and 6, directed to a method of effecting nonaddictive analgesia (pain reduction) in animals, were found to be anticipated by the applied prior art which disclosed the same compounds for effecting analgesia but which was silent as to addiction. The court upheld the rejection and stated that the applicants had merely found a new property of the compound and such a discovery did not constitute a new use.
As MPEP 2112 Requirements of Rejection Based on Inherency; Burden of Proof [R-10.2019], "[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."
All the claimed elements, lipidic alkyl chains decorating the core tryptophan amino acid structure are known in the art to make lipids. Thus the invention is a selective combination of the inventions by the prior arts done in a manner obvious to one of ordinary skill in the art. Patent for the combination of known elements wherein their functions remain the same withdraws “what is already known into field of its monopoly and diminishes resources available to skilled men”. Sakraida v. Ag Pro, Inc.189 USPQ 449, 425 US 273, (1976).
Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art.
Accordingly, the claims do not recite an unobvious distinction over the prior art. Further, a reference is relevant not only for what it expressly teaches, but also for what it would have conveyed to one of ordinary skill in the art. See In re Opprecht, 12 USPQ2d 1235, 1236 (Fed. Cir. 1989); In re Bode, 193 USPQ 12 (CCPA 1976). In light of the foregoing discussion, the Examiner finds that the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time the invention was made, in view of the cited references and the knowledge generally available in the art. Accordingly, the claims are rejected under 35 U.S.C. § 103.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: Enoki, Biophysical Journal 114, 1921–1935, April 24, 2018, FRET Detects the Size of Nanodomains for Coexisting Liquid-Disordered and Liquid-Ordered Phases.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Basuyaux, Chemical Communications (Cambridge, United Kingdom) (2019), 55(59), 8548-8551.
Basuyaux teaches
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corresponding to compound of claim 1 and 2:
R1=methyl, X=O, L=C12 alkyl of formula (I).
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.
Claim 9 is 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.
The last chemical structure in claim 9 is incomplete. As such the structural make-up of the claimed compound is unclear.
Claim Rejections - 35 USC § 112
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 1-11, 13, 15, 16, 18, 22, 23, 26, 28, 30 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for making compounds of the claimed formula I, does not enable for making and using any and all compounds of the formula. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The determination that "undue experimentation" would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the relevant factual considerations.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art.
All of the factors have been considered with regard to the claims, with the most relevant factors discussed below:
Formula of base claim 1 contains large number variable groups layered with substituents layered on substituents encompassing wide variety and number of conceivable structures that find little support in the specification. These substituents and hence the compounds of given formula are drawn to species that vary widely in physical and chemical properties such as size, molecular weight, stereochemistry, logP, acidity, basicity, etc. These factors are known in the art (see multiple references cited below) to greatly influence biological properties. It is acknowledged that making tryptophan derivatives entails elementary chemistry methods. The issue here is ‘use’ prong of the 112-1 enablement requirement.
Biological properties are unpredictable and are ultimately tide to the chemical structure, consistent with the wide breadth in IC50 shown in the Table for similar compounds. See “Role of the Development Scientist in Compound Lead Selection and Optimization” by Venkatesh, J. Pharm. Sci. 89, 145-154 (2000) (p. 146, left column). Likewise, J. G. Cannon, Chapter Nineteen in Burger's Medicinal Chemistry and Drug Discovery, Fifth Edition, Volume I: Principles and Practice, Wiley-Interscience 1995, pp. 783-802, 784, teaches many caveats in analog design such as
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Therefore the position taken is that based on the teachings of Venkatesh and Cannon, the wide breadth of the claims finds little support in the specification.
There is no working example or prior art citations of how to use the lipid formulation.
Examples 2 and 3 relate to how to use the three compounds made. How the issue here is whether these compounds, for example encapsulate any nucleic acids, is not found. Thus these Examples can be regarded not more than direction and guidance for assessment of potential use.
Given there is no working example or prior art citations for potential intended method of generically speculated use throughout the disclosure, there is no enabling disclosure for the method claims.
Note that in University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 at 1438, the screening for over 600 compounds was deemed to be undue. Applicant’s scope of the pictured formula far exceeds this number. The specification must teach how to make and use the invention, not teach how to figure out for oneself how to make and use the invention. In re Gardner, 166 USPQ 138 (CCPA 1970). Therefore, one skilled in the art could not make or use the claimed invention without undue experimentation.
There is no structural guidance such as pharmacophore definition disclosed in the specification to guide one of skill in the art to choose from the plethora possibilities recited for the variables.
There is a substantial gap between what is taught in the specification and what is being claimed. For these reasons, one skilled in the art would be faced with undue amount of research. The specification lacks disclosure sufficient to make and use the invention, in predictable manner, commensurate with the scope of the claims.
MPEP 2164.01(a) states, “A conclusion of Iack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. ln re Wright, 999 F.2d 1557,1562, 27 USPQ 2d 1510, 1513 (Fed. Cir. 1993).'' That conclusion is clearly justified here. Thus, undue experimentation would be required to make and use Applicants' invention.
Genetech Inc Vs Nova Nordisk 42 USPQ 2d 1001. “A patent is not a hunting license. It is not a reward for search but compensation for its successful conclusion and patent protection is granted in return for an enabling disclosure of an invention , not for vague intimations of general ideas that may or may not be workable.”
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIZAL S CHANDRAKUMAR whose telephone number is (571)272-6202. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at (571) 272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NIZAL S CHANDRAKUMAR/Primary Examiner, Art Unit 1625
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