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 .
Election/Restriction
Inventor’s election, without traverse (no arguments), of tranylcypromine HCL as the species elected to begin prosecution is acknowledged. The election/restriction is hereby made FINAL.
Claim Rejections - 35 USC § 112(a)
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 21-40 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 acaricidal compounds 1-3, 5-16, 18, 20, 22 and 24-29 of Table 1 (specification page 14), does not reasonably provide enablement for the universe of cytochrome P450 inhibitors (claims 21 and 34-40) nor the universe of compounds listed in claims (claims 22-33). 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.
With regard to rejections under 35 USC 112(a) or 35 USC 112, first paragraph, the following factors are considered (MPEP 2164.01(a)): a) Breadth of claims; b) Nature of invention; c) State of the prior art; d) Level of ordinary skill in the art; e) Level of predictability in the art; f) Amount of direction and guidance provided by the inventor; g) Working examples and; h) Level of experimentation needed to make or use the invention based on the content of the disclosure.
a) The claims are extraordinarily broad: “A method of inhibiting and/or killing Demodex on a subject and/or to prevent and/or treat a disease of the subject caused by Demodex infection, comprising: administering a cytochrome P450 inhibitor to the subject” (independent claim 21). Dependent claims 22-33 (each from claim 21) teach disparate lists of compounds, or substances (“…medical marijuana…”), as the cytochrome P450 inhibitor. Dependent claim 34 (from claim 21) teaches topical administration. Dependent claim 35 (from claim 21) teaches ocular or dermal administration. Dependent claim 36 (from claim 21) teaches an ophthalmic or dermatological preparation. Dependent claim 37 (from claim 21) teaches that the disease is an eye disease, a skin disease or an allergic disease. Dependent claim 38 (from claim 37) further defines the diseases. Dependent claim 39 (from claim 21) teaches xerophthalmia as the disease. Dependent claim 40 (from claim 39) teaches symptoms of xerophthalmia.
b,c) The nature of the invention is determined in part by the state of the prior art.
As even a cursory perusal of the pertinent medicinal arts reveals, Demodex infections are generally pharmaceutically treated by administration of specific compounds (rather than a broad, general class of compounds) via eye drops, or, for skin infections, topically.
d) The level of skill in the art is considered to be relatively high.
e) The level of predictability in the art is considered to be relatively low.
The basis of all modern medicine and biology is, of course, chemistry. Yet even under the best of circumstances, and more than two hundred years after Lavoisier laid the foundations of its modern practice, chemistry remains an experimental science. Neither the medicinal/biological arts nor the chemical arts upon which they are based have advanced to the point where certainty has replaced the need for clinical and/or laboratory experimentation.
Note that 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 in the art (MPEP 2164.03).
f,g) The amount of direction provided by the inventor is considered to be determined by the specification and the working examples. Inventor provides (page 13, Example 1) experimental data for 28 disparate compounds (page 14, Table 1), not all of which appear to have efficacy (note entries 4, 17, 19, 21 and 23) against mites. In Example 2 (page 15), an apparent clinical study, no administered compounds are even taught.
h) It would clearly require an extraordinary - and thus undue - amount of experimentation (clinical/laboratory trials, etc.) in order to determine if, in fact, the universe of cytochrome P450 inhibitors, or the universe of compounds listed in claims 22-33, are actually efficacious in the instant method. Significantly, the mixed efficacy of even the small set of 28 compounds of Table 1 would clearly preclude any reasonable extrapolation of the positive aspects of this data to encompass the efficacy of the universe of cytochrome P450 inhibitors, or the universe of compounds listed in claims 22-33.
Claim Rejections - 35 USC § 112(b)
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 21 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 meaning of the limitation “…cytochrome P450 inhibitor…” is unclear. Note, in particular, for instance, that inventor’s elected “P450 inhibitor,” tranylcypomine HCL, is generally classified in the art as a monoamine oxidase inhibitor – not a cytochrome P450 inhibitor per se. That being the case, inventor’s election inadvertently calls into question the true meaning of the instant limitation, since it, apparently, seeks to encompass much more than simply generally recognized cytochrome P450 inhibitors. Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. MPEP 2173.05(a)(III).
Clarification is in order.
Claim 23 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.
It is unclear how at least caffeine, famotidine and lidocaine, for example, can be described as cytochrome P450 inhibitors. These compounds are generally considered simply substrates of cytochrome P450, not inhibitors per se. (Analysis of other compounds listed in the claim may be similar, these are just three by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 24 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.
It is unclear how at least paclitaxel, mitoxantrone and docetaxel, for example, can be described as cytochrome P450 inhibitors. These compounds are generally considered simply substrates of cytochrome P450, not inhibitors per se. (Analysis of other compounds listed in the claim may be similar, these are just three by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 25 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.
It is unclear how at least amphetamine and clofibrate, for example, can be described as cytochrome P450 inhibitors. Amphetamines are best described only as competitive inhibitors, not inhibitors per se. Clofibrate, on the other hand, is known to increase expression of certain cytochrome P450 enzymes. (Analysis of other compounds listed in the claim may be similar, these are just two by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 26 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.
It is unclear how at least tamoxifen, simvastatin, doxorubicin and colchicine, for example, can be described as cytochrome P450 inhibitors. Tamoxifen, simvastatin and colchicine are generally considered simply substrates of cytochrome P450, not inhibitors per se. Doxorubicin, on the other hand, is known to inhibit some cytochrome P450 enzymes while at the same time increasing the expression of other cytochrome P450 enzymes. (Analysis of other compounds listed in the claim may be similar, these are just four by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 27 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.
It is unclear how at least felodipine and salmeterol, for example, can be described as cytochrome P450 inhibitors. These compounds are generally considered simply substrates of cytochrome P450, not inhibitors per se. (Analysis of other compounds listed in the claim may be similar, these are just two by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 28 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.
It is unclear how at least ethanol, olanzapine and naloxol, for example, can be described as cytochrome P450 inhibitors. Ethanol is known to inhibit some cytochrome P450 enzymes while at the same time increasing the expression of other cytochrome P450 enzymes. Olanzapine and naloxol are generally considered simply substrates of cytochrome P450, not inhibitors per se. (Analysis of other compounds listed in the claim may be similar, these are just three by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Furthermore, it is unclear to what compound/drug the name “…zucasin…” might refer. Is this perhaps a misspelling?
Claim 29 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.
It is unclear how at least chlorambucil, cholecalciferol and clobazam, for example, can be described as cytochrome P450 inhibitors. These compounds are generally considered simply substrates of cytochrome P450, not inhibitors per se. (Analysis of other compounds listed in the claim may be similar, these are just three by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Furthermore, the limitation “…medical marijuana…” is unclear. What is, or is not, medical marijuana is a legal or regulatory designation and as such will vary depending on jurisdiction and interpretations of the law. That being the case, the public would not be able to definitively determine the metes and bounds of the claim, since matters of law are, of course, dependent upon jurisdiction and always subject to change.
Claim 30 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.
It is unclear how at least insulin can be described as a cytochrome P450 inhibitor. Insulin’s effects on cytochrome P450 can be complex, but it is not an inhibitor per se. (Analysis of other compounds listed in the claim may be similar, insulin is just one by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 33 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.
It is unclear how at least felodipine, for example, can be described as a cytochrome P450 inhibitor. Felodipine is generally considered simply a substrate of cytochrome P450, not an inhibitor per se. (Analysis of other compounds listed in the claim may be similar, felodipine is just one by way of example.) Note that while an applicant may be his own lexicographer, applicant may not distort art-recognized terms. Note MPEP 2173.05(a)(III).
Claim 40 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 term easy in the limitation “…easy fatigue of eyes…” and the term thick in the limitation “…thick secretions…” are relative terms which renders the claim indefinite. The terms are not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. What is, or is not, easy fatigue of eyes or thick secretions would seem to be the most subjective of determinations.
Clarification is in order.
Claims 22, 31, 32 and 34-39 are also 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 claims all depend, or ultimately depend, from an indefinite claim yet do not completely relieve the indefiniteness. Dependent claims 22, 31, 32 and 34-39 are also, therefore, indefinite.
Markush Search
All claims have been examined with respect to formal matters.
The elected species has been searched and is deemed free of the prior art.
That being the case, the search was, therefore, expanded as called for under Markush examination practice, a compound-by-compound search, to include a single additional species. That species is: diosmetin.
All claimed but as yet unexamined subject matter which does not read on the above species is hereby withdrawn from consideration, for purposes of this Office Action, as being drawn to non-elected subject matter. This subject matter will be rejoined, as appropriate, as the Markush examination progresses.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 21, 22, 24 and 34-40 are rejected under 35 U.S.C. 102(a)(2) as being clearly anticipated by US 2023/0165921 A1 (which claims priority to 04/24/2020).
The reference teaches a method of significantly shortening the survival time of Demodex species utilizing decoctions of the traditional Chinese medicine Herba Taraxaci (abstract; page 2, [0037]-[0038]; page 5, [0093]; page 6, [0100]). Compounds contained in the Herba Taraxaci decoctions were then purchased and separately tested against Demodex mites (page 4, [0086]; page 6, [0103]). The compound diosmetin was found to be particularly effective against Demodex, as were as the compounds teraxerol and taraxasterol acetate (page 7, [0108]).
(The examiner notes for clarity of the record that diosmetin, teraxerol and taraxasterol are known in the art to be cytochrome P450 inhibitors (respectively: Biol. Pharm. Bull. (2009), 32(4), pp. 671-676, at page 674, Table 2 and page 676, column 1, text line 39; European Journal of Pharmacology (2015), 764, pp. 480-488 at page 481, Table 1, compound #10; and Hindawi, Oxidative Medicine and Cellular Longevity (2018), article ID: 8284107, 11 pages at page 1/1 abstract.)
The compositions are intended as topical treatment for ocular or dermal administration (page 2, [0046]). Ocular compositions may be in the form of eye drops, eye ointment, an ophthalmic gel, etc. (page 2, [0047]). Dermal compositions may be in the form of aerosol, powder, lotion, etc. (page 3, [0049]). The disease treated may be an ocular disease, a skin disease or an allergic disease (page 2, [0042]). The eye disease may be blepharitis,…abnormal eyelash alignment,…xerophthalmia, etc., wherein the symptoms may be itchy eyes,…foreign body sensation, etc. (page 2, [0043]).
Allowable Subject Matter
The elected species being free of the prior art (but note the 112(b) rejection of claim 21 above), any claim, or portion of a claim, drawn exclusively to this species constitutes allowable subject matter.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRIAN J DAVIS whose telephone number is (571)272-0638. The examiner can normally be reached M-F 8:30-5:00 PM EST.
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/BRIAN J DAVIS/Primary Examiner, Art Unit 1614 3/2/2026