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 .
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.
This office action is a response to applicant’s communication submitted June 9, 2023, wherein claims 1-13 were canceled and claims 14-24 were added.
Claims 14-24 are pending in this application.
Priority
This application is 371 of PCT/CN2021/136707 filed December 9, 2021 and claims foreign priority to CN202011453853.2 filed December 9, 2020. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been received. The Examiner notes an English translation has not been provided.
Claim Objections
Claim 21 is objected to because of the following informalities:
In claim 21 there should be a comma after the phrase “a liposome” as it is part of an extended list.
Appropriate correction is required.
Claim Interpretation
Claim 18 recites “The method of claim 18, wherein the atoms enriched in isotopic abundance are selected from 12C, 13C and 14C for carbon; 1H, 2H and 3H for hydrogen: 16O, 17O and 18O for oxygen; and 32S, 33S and 34S for sulfur.”. The broadest reasonable interpretation of this claim includes compounds of which atoms solely possess their naturally abundant isotope (i.e., 12C, 1H, 16O, and 32S), since these are naturally enriched in isotopic abundance compared to other isotopes.
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 14-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The specification, while being enabling for specific types of bacterial infections, such as P. aeruginosa, does not reasonably provide enablement for the treatment of all bacterial infections or prevention thereof as claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most clear connected, to make and use the invention commensurate in scope with these claims.
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)
relative skill in the art; (5) amount of direction provided by the inventor; (6) the level of
predictability in the art; (7) the existence of working examples; and (8) quantity of
experimentation needed to make or use the invention based on the content of the disclosure. All
of the factors have been considered with regard to the claim, with the most relevant factors
discussed below:
(1& 2) The breadth of the claims and nature of the invention: The claims are drawn to methods of treating, inhibiting, or preventing a bacterial infection comprising administering compounds that are fused ring phenolic compounds, and kits comprising said compounds and at least one diluent, buffer, or pharmaceutically acceptable excipient.
(3) The state of the prior art: While there are publications that describe methods of inhibiting specific bacterial growth with fused ring phenolic compounds, such as the compounds claimed, there is no evidence in the prior art that the claimed compounds would prevent bacterial infections from occurring as claimed. For example, Neville et al (Mbio, 2021, IDS filed May 9, 2024) teaches several compounds of the compounds claimed exhibit inhibitory action against PPK enzymes that are present in P. aeruginosa bacteria, as well as K. pneumoniae, A. baumanni, F. tularensis, and C. jejuni (pg. 3, table 1, para. 1). Neville discloses this mode of action has therapeutic potential in treating bacterial infections that possess this class of enzymes (i.e. PPK, pg. 2, paras. 2-3). Thus, in short, the art recognizes administering fused ring phenolic compounds that are PPK inhibitors have therapeutic potential in treating bacterial infections wherein the bacteria possess PPK, but not treatment of all bacterial infections or prevention thereof.
(4) The level of skill in the art: The level of skill in the art would be high, mostly likely at
the Ph.D. /MD level.
(5 & 7) The amount of direction provided by the inventor and the existence of working
examples: Applicant has not provided examples that demonstrate that the compounds claimed
is effective at treating all bacterial infections or preventing any bacterial infections as claimed. The instant specification has demonstrated that the compounds inhibit PPK enzymes (pg. 20, tables 1-2) and can treat pseudomonas aeruginosa infections in nematodes (pg. 21, para. 1), but does not demonstrate the compounds are effective at treating all bacterial infections or preventing any bacterial infections as claimed.
(6) The level of predictability in the art: The prior art does not teach a method of treating or preventing all bacterial infections by administering a compound that is a fused ring phenolic compound. Although some methods may treat specific bacterial infections, there is nothing in the prior art that indicates that treatment of all bacterial infections, or prevention thereof with fused ring phenolic compounds is possible.
(8) The quantity of experimentation necessary: Neither the instant specification nor the state of the art have demonstrated how compounds, such as the compounds claimed, can treat or prevent all claimed bacterial infections. An undetermined number of experimental factors utilizing a compound and its method for treating would have to be resolved by the practitioner and/or the patient for the following reasons: the factors are not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
Therefore, other than proposing an initial hypothesis, the entire burden of research
involved in utilizing the compounds claimed to treat or prevent all bacterial infections claimed would fall on the shoulders of the skilled artisan attempting to practice the claimed invention, presenting an undue burden of unpredictable experimentation.
Genentech, 108 F.3d at 1366, sates that, “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.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of the art and the lack of guidance or working examples, Applicant fails to provide information sufficient to practice the claimed invention without undue experimentation.
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.
Claims 18-21 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.
Regarding claims 18-19: Claim 18 recites “The method of claim 14, wherein the C, H, O, and S atoms in the compound are independently selected from atoms of natural abundance and atoms enriched in isotopic abundance.”. Claim 19 recites “The method of claim 18, wherein the atoms enriched in isotopic abundance are selected from 12C, 13C and 14C for carbon; 1H, 2H and 3H for hydrogen: 16O, 17O and 18O for oxygen; and 32S, 33S and 34S for sulfur.”. According to the instant specification the unnatural proportion of an isotope can be defined from the amount found in nature to the amount made up of 100% of the atoms in question (pg. 7, para. 5). The term "naturally abundant element" or "naturally abundant atom" used in the present invention refers, respectively, to an element or atom that has the most abundant atomic mass in nature (pg. 7, para. 6). .However, Gleason et al (Science, 1970) teaches that the natural abundance of deuterium can vary between sources and location (pg. 1085, abstract). For example, Gleason teaches Animals living in two sections of the country that differ in the amount of deuterium naturally present in the groundwater and existing on a diet of water from this environment along with grain and other foodstuffs grown there can be expected to have different amounts of deuterium in their body fluids (pg. 1086, col. 1, para. 2). Deuterium analyses on natural waters have shown variations as large as 50 percent (pg. 1086, col. 1, para. 3). Therefore, there is not a clear, absolute standard of what constitutes having greater than natural abundance of deuterium at a given position. Thus claims 18-19 are rendered indefinite.
Regarding claim 19: Claim 19 recites “The method of claim 18, wherein the atoms enriched in isotopic abundance are selected from 12C, 13C and 14C for carbon; 1H, 2H and 3H for hydrogen: 16O, 17O and 18O for oxygen; and 32S, 33S and 34S for sulfur.”. It is unclear whether the claims are attempting to state the naturally abundant atoms (i.e., 12C, 1H, 16O, and 32S) are meant to be further enriched than their natural state, or that the compounds would be inherently enriched in isotopic abundance given that these atoms are naturally abundant. According to the instant specification, "Non-isotopically enriched" are compounds in which all atoms or elements in the compound are naturally abundant isotopes, meaning that the atomic mass of all atoms or elements is the most abundant in nature. (pg. 7, last para.). Based on this definition, wherein the compounds possess atoms that are the naturally abundant isotopes, even if further enriched would be encompassed under “Non-isotopically enriched”. The lack of clarity of what is meant by the phrase “enriched in isotopic abundance” renders the claim indefinite. For Examination purposes, the claim will be interpreted wherein compounds possessing all naturally abundant atoms (i.e., 12C, 1H, 16O, and 32S) are encompassed by the claim.
Regarding claims 20-21: Claim 20 recites inter alia, “the pharmaceutical composition comprising one or more compound and at least one pharmaceutically acceptable carrier or diluent.”. Claim 21 recites, “The method of claim 20, wherein the at least one pharmaceutically acceptable carrier or diluent comprises a cream, an emulsion, a gel, a liposome or a nanoparticle.”. However, while liposomes or nanoparticles can be considered carriers, the recited creams, emulsions, and gels are not carriers or diluents according to standard definitions in the art, but rather types of preparations/formulations. According to the instant specification, “These carriers or excipients may be, for example, diluents such as calcium carbonate, sodium carbonate, lactose, calcium phosphate or sodium phosphate; granulating and disintegrating agents, such as com starch or alginic acid; binders such as starch, gelatin or gum arabic and lubricants such as magnesium stearate, stearic acid or talc.” (pg. 11, para. 2). The instant specification also states, “In some embodiments, the aforementioned pharmaceutically acceptable earners or diluents include creams, emulsions, gels, liposomes, or nanoparticles.” (pg. 5, para. 5). According to Wikipedia (Drug Carrier, 2025, cited on PTO-892), a drug carrier is a substrate used in the process of drug delivery, and include liposomes and nanoparticles (pg. 1, paras. 1-2). According to Wikipedia (Diluent, 2025, cited on PTO-892), diluents are inactive ingredients that are added to tablets in capsules in addition to the active drug (pg. 1, last para.). These additives may be used as binders, disintegrants, and include starch, cellulose derivatives, and magnesium stearate (a lubricant) (pgs. 1-2, bridging para.). The instant specification does not redefine carrier or diluents to mean anything other than what would be understood by one of ordinary skill in the art. Given the scope of what is encompassed by the phrase as described by the instant specification and recited in instant claim 21 and its conflict with what would be understood by one of ordinary skill in the art, claims 20-21 are rendered indefinite. In short, it is unclear what is encompassed by the phrases “carrier or diluents” due to the descriptions in the instant specification and instant claim 21.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 18-19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 18-19 which ultimately depend from claim 14 recite limitations aimed at limiting the atoms in the compounds recited to include atoms of natural abundance and atoms enriched in isotopic abundance (i.e. isotopes). However, there is no implication in claim 14 that any atoms other than the naturally occurring atoms in the recited compounds are encompassed by the claim. Thus, the addition of other isotopes recited by instant claims 18-19 expands, rather than limits claim 14.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 14 and 17-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kim (KR 20100070693, cited on PTO-892). The English translation has been provided by the Examiner.
Regarding claims 14 and 17-24: Kim teaches a method of treating bacterial infections utilizing pharmaceutical compositions comprising the compound of formula (I):
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236
255
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(English translation, pg. 6, formula 1, paras. 2-4). The pharmaceutical compositions can be administered orally or in the form of aqueous solutions or suspensions for parenteral use (including intravenous, intramuscular, or infusion, i.e. injection, English translation, pg. 7, para. 10). The compositions can be included in creams or gels by known means in the art (pg. 7, para. 10). Kim demonstrates the compounds are effective against S. aureus, B. subtillis, Enterococcus faecalis (English translation, pg. 10, para. 5).
Claims 14-19 and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong (WO 2017/009344, cited on PTO-892) as evidenced by Neville (Mbio, 2021, IDS filed May 9, 2024). The English translation of Wong has been provided by the Examiner.
Regarding claims 14-19: Wong teaches compounds and pharmaceutical compositions thereof for use in treating a pathogenic infection caused by Pseudomonas aeruginosa (English translation, abstract). Wong teaches one such compound of the invention is Myricetin, which has the following structure:
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92
136
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(Original document, pg. 21, table 1, 3rd structure, English translation, pg. 9, para. 9 ). Neville discloses that the pathogen Pseudomonas aeruginosa encode both PPK1 and PPK2 enzymes (pg. 1, abstract, importance).
Regarding claim 24: Wong teaches a composition comprising the inhibitors (i.e. myricetin) of the invention in buffer solution (i.e. a diluent) (English translation, pg. 11, paras. 8-12).
Conclusion
No claims are allowed in this action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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/S.L.G./ Examiner, Art Unit 1693
/ERIC OLSON/ Primary Examiner, Art Unit 1693